Acta Clinica Belgica最新文献

Objectives: To review the current indications for liver transplantation (LT) in cirrhosis, including evolving criteria for hepatocellular carcinoma (HCC) and other malignancies, how donor organ allocation is established, and to address challenges of long-term complications post-transplantation.

Methods: A comprehensive review of the literature was conducted to evaluate advancements in LT indications, pretransplant evaluation protocols, organ allocation strategies, and management approaches for long-term post-transplant complications.

Results: Liver transplantation remains the definitive treatment for cirrhosis and offers substantial survival benefits for patients with early-stage HCC. Recent advancements have expanded eligibility criteria to include patients with multiple comorbidities, advanced-stage HCC, and select malignancies, provided they meet specific selection criteria. The increasing demand for donor organs has driven innovations in donor pool expansion, which presents new challenges in recipient management, including the need for tailored pretransplant workups and strategies to mitigate long-term complications.

Conclusion: The field of liver transplantation continues to evolve, with broader indications and innovative approaches to donor pool expansion. These advancements necessitate careful patient selection, rigorous pretransplant evaluation, and effective long-term management strategies to optimize outcomes for transplant recipients.

Objectives: In this study, the capacity of End-tidal carbon dioxide (EtCO2) levels to predict the risk of major cardiovascular events (MACE) in patients diagnosed with acute coronary syndrome and the relationship between risk scoring systems (TIMI, GRACE, HEART) and EtCO2 values were examined.

Methods: EtCO2 values of the patients in the study were measured with a capnography device. Each patient's MACE status was recorded.

Results: The results we found in our study are as follows: (i) EtCO2 values were significantly lower in the group with MACE (n = 45) than in the group without MACE (n = 288) (p < 0.05). (ii) According to ROC analysis, EtCO2 was effective in predicting one-month mortality (AUC = 0.81, p < 0.00). (iii) The optimal EtCO2 cut-off point was 30 mmHg. This threshold value provided both sensitivity and specificity for the risk of MACE. (IV) Significant associations were found between EtCO2 and GRACE, TIMI and HEART scoring systems. EtCO2 values were significantly higher in the low-risk groups. (V) EtCO2 was significantly different in all three risk scoring systems in the non-MACE group, but only with the GRACE score in the MACE group.

Conclusion: This study demonstrated that EtCO2 is a valuable indicator for predicting the risk of MACE in patients with ACS.

The incidence of hepatocellular carcinoma (HCC) is rising, with a shift towards Metabolic Dysfunction-associated Steatotic Liver Disease becoming the dominant risk factor in Western countries. Significant advances in treatment have broadened the range of available therapeutic options. For this reason, clinical decision-making, along with a multidisciplinary team approach, plays a crucial role in improving patient outcomes. Following several landmark trials, immune checkpoint inhibitor-based therapy has now become the established first-line standard of care for advanced HCC. Additionally, the application of immunotherapy is shifting to include patients with earlier stages of HCC. Research on the combination with locoregional therapies for intermediate-stage HCC has recently reported positive results, and other phase III trials in the same patient population and early-stage HCC are currently in progress. Furthermore, a growing number of reports support the safety and efficacy of immunotherapeutic agents as potential adjuncts for downstaging of HCC, thus facilitating successful liver transplantation. We will discuss the published and ongoing trials in the expanding field of immune checkpoint inhibitor-based therapy for different stages of HCC.

Objectives: Urinary tract infections (UTIs) are an important cause of empiric antibiotic (over)treatment at the emergency department (ED). To enhance empiric antibiotic choices, mapping the national and local microbiology and antimicrobial resistance (AMR) patterns is crucial. This study aims to examine resistance patterns at a Brussels ED and to identify risk factors for AMR to evaluate current treatment guidelines and help combat AMR.

Methods: Adult patients undergoing urinalysis at the ED of a Brussels tertiary care hospital with positive urine cultures were included. Descriptive microbiological mapping of UTI or asymptomatic bacteriuria (ASB) micro-organisms was performed. Potential risk factors of antibiotic resistance in Gram-negative bacteria were assessed by using logistic regression analysis.

Results: Out of 96 patients with Gram-negative bacteria in urinary culture, the predominant uropathogen was Escherichia coli (58.3%), with 8.6% being extended spectrum beta-lactamase (ESBL)-producing strains. Overall, fosfomycin (29.2%) and nitrofurantoin (28.6%) showed the highest resistance rates. Ceftriaxone revealed lower resistance rates (13.1%) compared to ciprofloxacin (17.0%) and cefuroxime (18.4%). Temocillin exhibited the lowest resistance rate (8.2%) especially against ESBLs (0%). Ciprofloxacin resistance increased with age (OR 1.05 [1.01-1.10]) and recurrent UTIs (OR 4.79 [1.18-19.42]). Male gender was associated with higher odds of temocillin resistance (OR 5.79 [1.18-28.34]).

Conclusion: In the studied Belgian ED setting, ceftriaxone seems slightly safer than ciprofloxacin, especially for recurrent UTI patients. However, overall, and especially in patients at risk for ESBL-producing bacteria, temocillin would be an even better choice in our setting. National microbiological data should be reviewed to support recommending temocillin as a first-line antibiotic in patients presenting with upper UTI.

Objectives/background: We aimed to investigate routine urinalysis practices in Belgian laboratories and verify these findings against the 2023 European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) European Urinalysis Guideline.

Methods: A questionnaire was developed to collect information on pre- to postanalytical aspects of urine test strip and particle analysis. The questionnaire was distributed by Sciensano to all Belgian laboratories, licensed to perform urine particle analysis.

Results: Sixty-six percent of the Belgian laboratories (75/113) participated. The responding laboratories served physicians in private (25%), hospital (60%) and university hospital (15%) setting. All laboratories performed test strip and particle analysis, predominantly automatically (97% and 96%, respectively). In addition, most laboratories (87%) used intelligent verification criteria to optimize diagnostic accuracy. Almost all laboratories (≥90%) screened and reported a minimal biochemistry panel (glucose, protein, pH, ketones) and particle count (red and white blood cells). Independent of the technology, a notable variability was observed regarding medical cut-off values and advanced particle differentiation and reporting. Internal quality control was extensively performed for urine test strip (91%) and particle analysis (96%), while external QC was less common (32% and 36%, respectively). Consequently, only few laboratories were ISO15189 accredited for urine test strip (15%) and particle analysis (17%).

Conclusion: There is considerable variability in current urinalysis performed in Belgian laboratories. The 2023 EFLM urinalysis guideline has the potential to guide clinical laboratories towards improving their urinalysis practices. Additional efforts are required to implement these recommendations into clinical practice in Belgium.

Background: ANCA-associated vasculitis (AAV), and nephrotic syndrome encompassing diseases including minimal change disease (MCD), focal and segmental glomerulosclerosis (FSG), membranous nephropathy (MN), remain a challenge due to their varied immunological characteristics. Recent therapeutic advancements have highlighted the importance of understanding these diseases' immunological landscapes.

Methods: This study analyzed transcriptomics data from renal glomerular tissues of patients with AAV, FSG, MCD, MN, and normal controls. Utilizing an immune-related gene set of 883 genes, methods including Gene Set Variation Analysis (GSVA), LASSO regression, and Weighted Correlation Network Analysis (WGCNA) were used. Predictions of immune cell compositions were made through CIBERSORT, TIMER, MCPcounter, and quanTIseq algorithms.

Results: The study revealed distinct immunogenetic pathways enriched in each disease: hematopoietic cell lineage in ANCA, linoleic acid metabolism in FSG, PPAR signaling in MCD, and drug metabolism in MN. Classifiers based on immune gene expression showed high accuracy (AUC: ANCA 0.812, FSG 0.99, MCD 1, MN 0.888). Co-expression modules and PPI networks highlighted unique pathways for each disease. Predictions of immune cell composition showed elevated macrophages in FSG and MN, with Treg levels elevated across all four diseases compared to normal controls and highest in FSG. Correlation analyses demonstrated significant associations between classifier scores and immune cell types.

Conclusion: This study offers accurate classifiers for AAV, FSG, MCD, and MN, and reveals distinct immunological pathways. These findings advance personalized treatments and highlight potential therapeutic targets in AAV and nephrotic syndrome. Further research should validate these results for clinical applications.

Objectives: This study aimed to evaluate an expanded matrix-assisted laser desorption-ionization-time of flight mass spectrometry (MALDI-TOF MS) database for the identification of Haemophilus species other than H. influenzae (Hi).

Methods: A total of 144 Haemophilus species, cultured from respiratory samples from people (living) with cystic fibrosis, were identified with MALDI-TOF MS and 16S rRNA sequencing. Of these, 99 Haemophilus strains showed >99% similarity with the best matching strain in the National Center for Biotechnology Information (NCBI) database and were assigned to a single Haemophilus subspecies using both MALDI-TOF MS and 16S rRNA sequencing. The MS profiles of a subset of strains (n = 58/99) were added to the Bruker MALDI-TOF MS database. Subsequently, 270 different strains that were analyzed previously in a routine setting were re-analyzed.

Results: 16S rRNA sequencing reliably identified 99/144 Haemophilus strains (>99% similarity). H. haemolyticus 16S rRNA identification was suboptimal since only 3/21 H. haemolyticus strains attained a similarity of >99% with H. haemolyticus 16S rRNA sequence in the NCBI database. Expansion of the MALDI-TOF MS database improved the number of reliable identifications only moderately for H. haemolyticus, H. influenzae and H. paraphrohaemolyticus (<10%). By contrast, improved identification was more outspoken for H. parahaemolyticus, H. parainfluenzae, H. sputorum and H. pittmaniae (>85%).

Conclusion: 16S rRNA sequencing is a valuable method for the identification of Haemophilus sp. other than Hi. Expansion of the MALDI-TOF MS database, based on 16S rRNA sequencing results, increased the proportion of reliable identifications and in this study resulted in an increase of 10% of Haemophilus sp. other than Hi strain identifications.

Introduction: Large B-cell lymphomas (LBCL) are the most frequently aggressive B-cell non-Hodgkin lymphomas. Anti-CD19 chimeric antigen receptor (CAR)-T cell therapy has emerged as a new, powerful treatment for relapsed or refractory (R/R) disease. Two CAR-T cell products, tisagenlecleucel (tisa-cel,) and axicabtagene ciloleucel (axi-cel), are reimbursed in Belgium for R/R LBCL beyond second line.

Objectives and methods: We conducted a retrospective cohort study to report the outcome with tisa-cel and axi-cel for R/R LBCL beyond second line in the years 2019-2023 at the University Hospitals Leuven for 79 patients selected for apheresis and CAR-T infusion.

Results: Eleven patients (14%) did not proceed to CAR-T cell infusion. For infused patients (n = 68), the best overall response rate (ORR)/complete response (CR) rate was 64%/49% for tisa-cel and 88%/66% for axi-cel (p = 0.04 for ORR). After a median follow-up of 13.8 months, progression-free survival (PFS) and overall survival (OS) at 1 year were 30% and 43% for tisa-cel and 48% and 62% for axi-cel. Cytokine release syndrome (CRS) (all grades/grade ≥3) occurred in 82%/9% after tisa-cel and in 97%/0% after axi-cel. Immune effector cell-associated neurotoxicity syndrome (ICANS) (all grades/grade ≥3) occurred in 24%/18% after tisa-cel and in 54%/40% after axi-cel. The non-relapse mortality in the infusion cohort was 13%.

Conclusion: Our real-world data show high and durable response rates, with a non-significant trend towards a higher efficacy and higher toxicity for axi-cel compared to tisa-cel. Our results are in line with other real-world registries except for a shorter median OS and more high-grade ICANS.

Objective: Describe the prevalence and characteristics of people living with HIV (PLWH) in Belgium with limited/exhausted treatment options.

Methods: A cross-sectional, multicenter study involving adult treatment-experienced individuals with limited/exhausted treatment options defined as having a multi-drug resistant HIV-1 or a history of multiple treatment changes. The primary outcome was to determine the prevalence of these individuals and classify them based on their two most recent consecutive HIV-1 viral loads (VLs): suppressed (2 VLs < 50 copies/mL), intermediate (≥1 VL between 50-200 copies/mL), or unsuppressed (2 VLs > 200 copies/mL). Secondary outcome was to characterize the participants included in this analysis.

Results: There were 119 individuals included (prevalence of 0.97%; 119 of 12 282 in care). The majority were aged > 50 years (88.2%), women represented 35.3%, and individuals were primarily White (54.7%). Median (IQR) CD4⁺ T-cell count was 635 (400-875) cells/µL and most (42%) were on a 3-drug ART regimen. Overall, 87.4% were classified as suppressed, 9.2% as intermediate, and 3.4% as unsuppressed. On multivariable analysis, CD4⁺ T-cell count < 200 cells/µL was associated with being classified as intermediate or unsuppressed (p = 0.004).

Conclusion: In this analysis of PLWH in Belgium, individuals with limited/exhausted treatment options represented a small fraction. Most were on a 3-drug ART regimen, were virologically suppressed, and had a CD4⁺ T-cell count within normal range. A small proportion were not virologically suppressed while others, despite being suppressed, were on ≥ 4-drug ART regimens. As such, new therapeutic options are needed to achieve and maintain virologic suppression in such individuals while decreasing their pill burden.

Patients with hepatoblastoma featuring carcinoma characteristics have better outcomes after liver transplantation, than after chemotherapy and resection. Possibly this should be extrapolated to aggressive subtypes of hepatocellular carcinomas in non-cirrhotic livers, where early liver transplantation might also be indicated. However, the risks associated with liver transplantation and immunosuppressive treatment after liver transplantation are once again demonstrated by this case of a 32-year-old women with a negative personal and familial history of liver diseases. She underwent transplantation (DBD) for a hepatocellular carcinoma with stem cell features (HCC-HS; an aggressive 'hepatoblast subtype' of hepatocellular carcinoma) after chemotherapeutical downstaging techniques failed to sufficiently downstage the tumor. Despite being on conventional immunosuppressive regimens (tacrolimus and mycophenolate mofetil with initial corticosteroids tapered), this patient still developed two severe rejection episodes, one of which necessitated retransplantation (DCD). Both episodes were preceded by alterations in tacrolimus trough levels, either intentionally, when tacrolimus was reduced within a nephroprotective regimen, or unintentionally, when rifampicin, a CYP3A4 inducer, significantly lowered the trough levels. Together, these episodes stress the importance of therapeutic drug monitoring of tacrolimus. Furthermore, the patient experienced an everolimus-linked drug-induced thrombotic microangiopathy, underwent multiple ERCPs for an anastomotic stricture and only one and a half year after the first liver transplantation she already suffers from long-term immunosuppressive-related side effects such as impaired glucose tolerance, hypertension and a potential cardiomyopathy. At present, she is still alive and experienced no recurrence of her primary tumor. Her case underscores the significant challenges in post-liver transplantation care.