Clinical reporting following the quantification of cerebrospinal fluid biomarkers in Alzheimer's disease: An international overview.

INTRODUCTION: The current practice of quantifying cerebrospinal fluid (CSF) biomarkers as an aid in the diagnosis of Alzheimer's disease (AD) varies from center to center. For a same biochemical profile, interpretation and reporting of results may differ, which can lead to misunderstandings and raises questions about the commutability of tests. METHODS: We obtained a description of (pre-)analytical protocols and sample reports from 40 centers worldwide. A consensus approach allowed us to propose harmonized comments corresponding to the different CSF biomarker profiles observed in patients. RESULTS: The (pre-)analytical procedures were similar between centers. There was considerable heterogeneity in cutoff definitions and report comments. We therefore identified and selected by consensus the most accurate and informative comments regarding the interpretation of CSF biomarkers in the context of AD diagnosis. DISCUSSION: This is the first time that harmonized reports are proposed across worldwide specialized laboratories involved in the biochemical diagnosis of AD.

Clinical impact of ceruloplasmin levels at ANCA-associated vasculitis diagnosis.

OBJECTIVES: Ceruloplasmin is an inhibitor of myeloperoxidase (MPO) activity that plays an important role in the pathophysiology of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). This study aimed to evaluate the prognostic impact of serum level of ceruloplasmin at diagnosis in patients with anti-MPO antibody-positive AAV. METHODS: This retrospective monocentric study in Caen University Hospital involved all consecutive adult anti-MPO antibody-positive patients with microscopic polyangiitis or granulomatosis with polyangiitis, diagnosed between January 2010 and January 2022 with available serum sample at inclusion. Patients outcomes were analyzed from two subgroups constituted according to the median serum level of ceruloplasmin. The same analyses were then performed in anti-proteinase 3 (PR3) antibody-positive patients. RESULTS: Within the 92 patients analyzed, 50 patients had anti-MPO antibodies with a median ceruloplasmin level of 0.44 [quartiles 1-3, 0.40-0.49] g/L and a median Birmingham Vasculitis Activity Score of 19 [14-22]. After a median follow-up period of 40 [22-86] months, 13 (26%) patients had died: 10 (40%) in the low ceruloplasmin group and 3 (12%) in the high ceruloplasmin group (p = 0.03), with a significantly worse survival rate in the low ceruloplasmin group (p = 0.021). No significant differences in relapse rate or renal failure was observed between the two groups. The same analyses performed in the group of AAV patients with anti-PR3 antibody did not show any differences. CONCLUSION: In anti-MPO AAV patients, serum level of ceruloplasmin at diagnosis seems to be associated with a significant impact on survival.

Ferritin as a predictive biomarker of severity in Covid-19 / La ferritine comme biomarqueur prédictif des formes sévères de Covid-19

Background: To prevent the crisis-level shortage of beds in hospitals and for a more efficient support, it's necessary to early identify coronavirus disease-19 (Covid-19) patients at risk to develop a severe form of the disease. Objective: The goal of our study was to determine whether biological markers, including the serum ferritin, could predict the severity of the Covid-19. Methods: One hundred and seventy-one patients, who were admitted to Caen University Hospital, were included retrospectively with a positive diagnosis of Covid-19 by RT-PCR. A serum ferritin measurement was performed for all patients. They were further classified either into a non-severe or a severe group based on their hospitalization in intense care unit (ICU) for mechanical ventilation or death. Results: Univariate analysis revealed a significant association between increased serum ferritin and CRP levels, obesity, CT scan lesions, pathological respiratory rate, decreased PaO2/FiO2 ratio, the NEWS-2 score and the severe (n = 59) vs the non-severe (n = 112) outcome of Covid-19 patients. However, in a multivariate analysis, only CRP and obesity were associated with the severe form of Covid-19. Conclusion: While pathological level of serum ferritin at admission is associated with severe form of Covid-19, combination of increased CRP level and obesity would better predict the severity of the disease.

Pour une meilleure prise en charge, il est nécessaire de pouvoir identifier précocement les patients atteints de la Covid-19 susceptibles de développer une forme sévère. L'objectif de notre étude était de déterminer si des marqueurs biologiques, notamment la ferritinémie, peuvent prédire la sévérité de la Covid-19. Nous avons inclus de manière rétrospective 171 patients au CHU de Caen avec un diagnostic de Covid-19. Les patients devaient avoir un bilan biologique incluant la ferritinémie à l'admission et ont été classés en formes sévères (n = 59, hospitalisation et ventilation invasive en soins intensifs ou en réanimation, et/ou décès) et non-sévères (n = 112, tous les autres patients). L'analyse univariée a montré une association entre les formes sévères de Covid-19 avec les niveaux élevés de ferritine et de CRP, l'obésité, les lésions pulmonaires, la fréquence respiratoire élevée, la diminution du ratio PaO2/FiO2 et le score de NEWS-2. Cependant, en analyse multivariée seules la CRP et l'obésité montraient une association avec les formes sévères. En conclusion, alors que la ferritinémie élevée est associée à un risque accru de développer une forme sévère de la Covid-19, la CRP et la présence d'une obésité seraient de meilleurs marqueurs prédictifs.

Value of the synovial C-reactive protein test in the diagnosis of total hip and knee periprosthetic joint infections: A case-control study.

INTRODUCTION: The diagnosis of periprosthetic joint infection (PJI) can be challenging and rests on several principles. The use of diagnostic biomarkers, such as the synovial C-Reactive Protein (CRP), seems promising. The purpose of this study was to determine whether synovial CRP was a more discriminating test than serum CRP for the diagnosis of hip and knee PJI. MATERIALS AND METHODS: In total, 194 patients were included in this single center prospective study: 42 primary arthroplasties (control group [CG]), 111 revisions for aseptic prosthesis (aseptic revision group [ARG]), and 41 revisions for septic prosthesis (septic revision group [SRG]) based on the Musculoskeletal Infection Society (MSIS) criteria. RESULTS: The serum and synovial CRP levels were significantly higher in the SRG than the other two groups (SRG serum CRP=75.6mg/L vs. ARG serum CRP=6mg/L and CG serum CRP=2.7mg/L, p<0.001; SRG synovial CRP=31.5mg/L vs. CG synovial CRP=2.6mg/L and ARG synovial CRP=1.7mg/L, p<0.001). The positive likelihood ratios (LR+) were very similar for both the synovial CRP cut-off value of 4.4mg/L (LR+=7.04; sensitivity [Se] 82.5%, specificity [Sp] 88.3%) and the serum CRP cut-off value of 9mg/L (LR+=6.3; Se 87.5%, Sp 86.1%). CONCLUSION: This study showed that synovial CRP testing was not more discriminating than serum CRP in the diagnosis of hip and knee PJI. A serum CRP level greater than 9mg/L was a sign of PJI. LEVEL OF EVIDENCE: III; case-control study.

Clinical Effect of Alpha-1 Antitrypsin Deficiency in Antineutrophil Cytoplasmic Antibody-associated Vasculitis: Results from a French Retrospective Monocentric Cohort.

OBJECTIVE: Deficiency in alpha-1 antitrypsin (AAT) is a possible pathogenic cofactor in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, the clinical effect of AAT deficiency remains poorly established in this setting. This study aimed to describe the clinical phenotypes and outcomes of AAV according to AAT phenotypes. METHODS: This study was conducted retrospectively at Caen University Hospital and included all consecutive granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) patients with positive proteinase 3-ANCA or myeloperoxidase-ANCA, from January 2000 or September 2011, respectively, to June 2016. AAT dosage (nephelometry) and phenotyping (isoelectric focusing in agarose gel) were performed. RESULTS: Among the 142 patients with AAV, including 88 GPA and 54 MPA, 102 (72%) had the MM phenotype, 5 (4%) had a nonpolymerogenic M-variant phenotype, 18 (13%) had the deficient allele MZ, 12 (8%) had MS, 2 (1%) had ZZ, 2 (1%) had SZ, and 1 (1%) had SS. M, Z, and S allele frequencies were 84%, 8%, and 6%, respectively. No association was observed between AAT deficiency and ANCA subtype or AAV phenotype, except for intraalveolar hemorrhage (IAH), which was more frequent in patients harboring at least 1 of the deficient Z or S alleles than in those without any deficient alleles (p < 0.01). Global, renal, or relapse-free survival rates were similar for all subgroups. CONCLUSION: This study shows that AAT deficiency confers, independently of ANCA subtype, a higher risk of IAH. Prospective studies are required to refine these data and to assess the need for replacement therapy in AAT-deficient patients with AAV.

[Which are the significance of low level of glycated hemoglobin A1c?] / Hémoglobine glyquée A1c basse : quelles significations ?

Glycated hemoglobin A1c (HbA1c) reflects the mean blood glucose over the lifespan of red blood cells and has become a valuable tool both for diagnosis and monitoring of diabetes. Nevertheless, some factors may under-estimate the HbA1c value, compromising its application. The aim of this retrospective study was to evaluate the incidence rate of HbA1c lower than 4% and to identify some clinical and biological factors that can potentially reduce the HbA1c level. Between January 1st 2015 and October 1st 2017, we selected 17 patients with a HbA1c level lower than 4% that were measured in our laboratory of biochemistry at the university medical center of Caen. From the medical records, we identified medical conditions, treatments and biological parameters that could potentially explain a decrease of HbA1c level. Meanwhile the measurement of HbA1c, 8/16 patients had hemoglobin level lower than 100 g/L and 5/6 presented with reticulocytosis (>100 G/L). Ten patients over 17 suffered from hepatopathy (cirrhosis from various etiologies) with abnormal liver blood tests for 12 patients. Two patients showed hemolytic anemia and another one was investigated for hypoglycemia due to congenital hyperinsulinism. Finally, 3 patients were treated with drugs known to lower HbA1c levels. True hypoglycemia periods but also other circumstances which are known to alter erythrocytes lifespan or the glycation process may decrease HbA1c level. Such biological result should be critically interpreted and alternative biological markers should be considered.

Is it worth to report the presence of a single and additional band in the cerebrospinal fluid detected by isoelectrofocusing?

Despite the revisions of the Mac Donald criteria of multiple sclerosis (MS) in 2010, the cerebrospinal fluid (CSF) analysis by isoelectrofocusing (IEF) remains useful for atypical presentations of MS. The IEF is considered as positive when at least two or more additional bands are detected in the CSF by comparison with the patient's serum but sometimes, the IEF interpretation is more difficult. The goal of our study was to determine the significance when a single band in the CSF is detected by IEF. We conducted a retrospective study on 990 patients who underwent a lumbar puncture followed by a CSF analysis by IEF. Only 2% display such IEF profile (i.e. single and additional band in the CSF). A diagnosis of clinically isolated syndrome or MS was evidenced in 4 among those 21 patients. In conclusion, our data suggest that even if the presence of a single and additional band in the CSF is a rare situation, it should be mentioned to clinicians to not exclude the hypothesis of an inflammatory demyelinating disease of the central nervous system.