A case of functional vitamin B12 deficiency after recreational nitrous oxide use

Highlights Vitamin B12 and holotranscobalamin may be normal in chronic nitrous oxide users Nitrous oxide induces a defect in vitamin B12-mediated functions Homocysteine and methylmalonic acid help identify N2O-users with B12 deficiency The recreational use of nitrous oxide as laughing gas becomes a real public health issue among adolescents and young adults. Chronic use is deleterious and can lead to severe neurological disorders. Nitrous oxide inactivates vitamin B12, and the functional defect of vitamin B12 plays a major role in the pathogenesis of nitrous oxide-related neurological disorders. Here we report the case of a 22-year-old woman who came to the hospital after an unexplained loss of consciousness. She exhibited typical features of vitamin B12 or folate deficiency such as macrocytic anemia and hypersegmented neutrophils. However, serum concentrations of folate and vitamin B12 were normal. In contrast, circulating concentrations of total homocysteine and methylmalonic acid were significantly increased. These results clearly indicated a defect in vitamin B12 functions. The reason for this defect was clarified when she revealed that she had been consuming nitrous oxide recreationally for over a year. The present case points out the challenges in diagnosing vitamin B12 deficiency in the context of nitrous oxide abuse due to normal concentrations of total serum vitamin B12 in a significant proportion of cases. The medical community should be aware of how difficult it can be to interpret B12 status in this specific population

Extreme hyperferritinemia in the setting of acute myeloid leukaemia: a case report of hemophagocytic lymphohistiocytosis.

Introduction: Major hyperferritinemia is a rare feature in clinical laboratories associated with a wide variety of disorders, including hemophagocytic lymphohistiocytosis (HLH). The diagnosis of HLH is based on clinical and biological criteria, such as those proposed by the Histiocyte Society. However, several of these criteria are not relevant in the specific setting of hematologic malignancies. Materials and methods: A 69-year-old male was treated for an acute myeloid leukaemia. On day 15 after the start of chemotherapy, he developed severe sepsis with high fever, low blood pressure and hepatosplenomegaly. Results: Blood tests were marked by extreme hyperferritinemia (191,000 µg/L, reference range: 26-388 µg/L) with increased C-reactive protein (87.0 mg/L) and procalcitonin (1.94 µg/L) and aspartate aminotransferase (499 U/L 37 °C) in the setting of chemotherapy-induced aplasia. This unusual extreme ferritinemia led to suspect HLH triggered by an invasive infection. Under intensive treatment, the clinical status improved and ferritin levels significantly decreased. Conclusions: The diagnosis of HLH is usually based on clinical and biological criteria, mainly fever, splenomegaly, cytopenias, hypertriglyceridemia, hypofibrinogenemia, hemophagocytosis and hyperferritinemia. In this patient, the diagnosis of HLH was challenging because several criteria, such as hypertriglyceridemia, hemophagocytosis and hypofibrinogenemia, were absent. In addition, some criteria of HLH are not relevant in the setting of hematologic malignancy, in which fever, splenomegaly, cytopenias and elevated lactate dehydrogenase are commonly observed independently of HLH. This unusual case of extremely high ferritinemia emphasizes the important weight of the ferritin level for the diagnosis of HLH in adult patients in the setting of hematologic malignancies

Composition en phospholipides et sphingolipides des lipoprotéines de haute densité (HDL) chez les diabétiques de type 1

Objectif. En raison de l importance des phospholipides (PL) et sphingolipides (SPL) dans la fonctionnalité des HDL, nous avons recherché une modification de la composition en PL et SPL des HDL chez 43 patients DT1 et 36 sujets témoins à l aide d une analyse par chromatographie liquide couplée à la spectrométrie de masse en tandem. Résultats. Les HDL étaient appauvries en sphingosine-1-phosphate au cours du DT1 (581 +- 165 versus 659 +- 148 nmol/l chez les sujets DT1 et témoins respectivement, p = 0,033). La proportion de PL par rapport à l ensemble des constituants des HDL était augmentée chez les sujets DT1 (+ 9 %, p < 0,001). L activité PLTP était augmentée de 21 % au cours du DT1 (p = 0,001). Conclusion. Ces modifications sont susceptibles de contribuer à l altération de la fonctionnalité des HDL observée au cours du DT1DIJON-BU Médecine Pharmacie (212312103) / SudocSudocFranceF

Clinical and Imaging Outcomes after Vitamin D Supplementation in Patients with Multiple Sclerosis: A Systematic Review

The link between vitamin D and multiple sclerosis (MS) has been suggested in epidemiological, genetic, immunological, and clinical studies. The aim of the present systematic review of the literature was to assess the effects of vitamin D supplementation on clinical and imaging outcomes in patients with MS. The outcomes we assessed included relapse events, disability progression, and magnetic resonance imaging (MRI) lesions. The search was conducted using PubMed, ClinicalTrials.gov, and EudraCT databases, and it included records published up until 28 February 2023. The systematic review was reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 guidelines. Nineteen independent clinical studies (corresponding to 24 records) were included in the systematic review. The risk of bias in randomized controlled trials (RCTs) was analyzed using the Cochrane risk-of-bias tool. Fifteen trials investigated relapse events, and most of them reported no significant effect of vitamin D supplementation. Eight of 13 RCTs found that vitamin D supplementation had no effect on disability [assessed by Expanded Disability Status Scale (EDSS) scores] compared to controls. Interestingly, recent RCTs reported a significant reduction in new MRI lesions in the central nervous system of MS patients during supplementation with vitamin D3

Vitamin B12 Status in Recreational Users of Nitrous Oxide: A Systematic Review Focusing on the Prevalence of Laboratory Abnormalities

The recreational use of nitrous oxide (N2O) as “laughing gas” is a growing problem. The chronic toxicity of N2O is mainly due to its ability to oxidize vitamin B12, making it dysfunctional as a cofactor in metabolic pathways. This mechanism plays a major role in the development of neurological disorders in N2O users. The assessment of vitamin B12 status in N2O users is important but challenging due to the lack of decrease in total vitamin B12 in most cases despite genuine vitamin B12 functional deficiency. Other biomarkers, such as holotranscobalamin (holoTC), homocysteine (tHcy) and methylmalonic acid (MMA), are interesting candidates to properly assess vitamin B12 status. Here, we conducted a systematic review of case series in order to assess the prevalence of abnormal values of total vitamin B12, holoTC, tHcy and MMA in recreational N2O users, which is an important prerequisite for determining the best screening strategy in future guidelines. We included 23 case series (574 N2O users) from the PubMed database. Total circulating vitamin B12 concentration was low in 42.2% (95% confidence interval 37.8–46.6%, n = 486) of N2O users, while 28.6% (7.5–49.6%, n = 21) of N2O users had low circulating concentrations of holoTC. tHcy levels were elevated in 79.7% (75.9–83.5%, n = 429) of N2O users, while 79.6% (71.5–87.7%, n = 98) of N2O users had increased concentrations of MMA. In summary, the increases in tHcy and MMA were the most prevalent abnormalities, and should be measured alone or in combination in symptomatic N2O users rather than total vitamin B12 or holoTC

Evaluation of the new restandardized 25-hydroxyvitamin D assay on the iSYS platform

IF 2.434International audienceBACKGROUND:25-hydroxyvitamin D [25(OH)D] is the most reliable biomarker of vitamin D status, but until now 25(OH)D assays have suffered from inter-laboratory and inter-assay discrepancies. In the setting of the international Vitamin D Standardization Program, Immunodiagnostic Systems (IDS) recently reformulated and restandardized the 25(OH)D immunoassay available on the automated iSYS platform. In the present study, we evaluated this new generation of the 25(OH)D immunoassay (IS-2500).METHODS:Repeatability and within-laboratory imprecision were verified according to the Clinical and Laboratory Standards Institute EP15-A3. Results from the sera of 63 patients were compared with those obtained with the previous iSYS method (IS-2700S) using Passing-Bablok and Bland-Altman analysis. The prevalence and bias-adjusted kappa (PABAK) coefficient was calculated to assess the agreement of vitamin D status provided by the two iSYS immunoassays. Fourteen Vitamin D External Quality Assessment Scheme (DEQAS) samples were used to evaluate inaccuracy.RESULTS:Using the EP15-A3 protocol, repeatability and within-laboratory imprecision obtained with the new iSYS method were lower than 6% and 8%, respectively. These results are consistent with the manufacturer's claims. In more adverse conditions (50 measurements over 15days with multiple calibrations), the within-laboratory imprecision was 14.8% (39nmol/L) and 7.7% (155nmol/L). 25(OH)D concentrations measured with the new assay showed a strong correlation with those provided by the previous version (r=0.969, p<0.0001). The Passing-Bablok regression equation was as follows: new assay=1.079 x (previous assay) - 3.6nmol/L. The PABAK coefficient of 0.810 reflected almost perfect agreement between the two immunoassays to classify patients according to their vitamin D status (85.7% of agreement). Using DEQAS samples, the mean inaccuracy bias was lower than 5% when the new iSYS method was compared with LC-MS/MS methods and the NIST reference measurement procedure.CONCLUSION:The new generation of the iSYS immunoassay evaluated in this study meets requirements for routinely measuring 25(OH)D levels in clinical laboratories.Copyright © 2017. Published by Elsevier Inc

Assessment of folate status in obese patients: Should we measure folate in serum or in red blood cells?

BACKGROUND: Recent studies revealed that obesity is associated with decreased serum but at the same time increased red blood cell (RBC) folate concentrations compared with lean subjects, thus casting doubt upon the agreement between serum and RBC folate measurements for assessing folate status. This work aimed to determine whether these two metrics lead to the same classification of folate status in obese patients. METHODS: RBC and serum folate concentrations were measured with a chemiluminescent immunoassay in 263 adults with body mass index >/=30 kg/m2 and without previous bariatric surgery. Among them, 68.1 % were eligible for bariatric surgery. Each serum and RBC folate result was classified as deficient or not according to thresholds recommended by the kit manufacturer (model A) or by the World Health Organization (model B). The agreement between serum and RBC folate results was evaluated using the proportion of overall agreement and the prevalence-adjusted bias-adjusted kappa (PABAK) statistics. RESULTS: The overall percentage agreements between serum and RBC measurements were 91.6 % (95 % CI 87.6-94.7 %) and 92.4 % (95 % CI 88.5-95.3 %) with PABAK coefficients of 0.87 (95 % CI 0.82-0.93) and 0.88 (95 % CI 0.83-0.94) in the models A and B, respectively, corresponding to almost perfect agreement. The same was true in the subgroup of patients eligible for bariatric surgery. Gender, age, and BMI did not influence the quality of agreement between the two parameters. CONCLUSIONS: The present study showed that folate measurements in serum and in RBC display similar performances to assess folate status in obese patients

Interférences des traitements par biotine avec les immunodosages : il est temps de trouver une solution à long terme !

IF 0.908 (2017)Lettre à l'éditeur ("La Presse Médicale" vol. 47 n°1)https://www.sciencedirect.com/science/article/pii/S075549821730461X?via%3Dihu

CO-74: Altérations majeures du sphingophospholipidome des lipoprotéines de haute densité (HDL) de patients avec syndrome métabolique et glycémie normale

IF 4.693International audienc

Major changes in the sphingophospholipidome of HDL in non-diabetic patients with metabolic syndrome

IF 3.942International audienceObjective: Phospholipids and sphingolipids play a critical role in the protective effects of HDL against atherosclerosis. These properties are impaired in patients with metabolic syndrome, before the development of diabetes. We thus investigated whether HDL from patients with metabolic syndrome but normal fasting glycaemia present abnormalities in their sphingophospholipid profile.Methods: Using liquid chromatography/tandem mass spectrometry, we quantified the different species of the main phospholipids and sphingolipids in the HDL2 and HDL3 from 26 obese patients with metabolic syndrome but normal fasting glycaemia and 50 controls.Results: Phosphatidylcholines, when expressed as the relative amount compared with total phospholipids and sphingolipids, were similar in both HDL2 and HDL3 in the two groups. Lysophosphatidylcholines were 41% (p = 0.0002) and 86% (p < 0.0001) higher in HDL2 and HDL3, respectively, from patients with metabolic syndrome than in those from controls. Phosphatidylinositols were also higher in HDL2 and HDL3 (respectively, +60 and + 103% (p < 0.0001)). In contrast, both HDL2 and HDL3 from patients with metabolic syndrome showed lower proportions of phosphatidylethanolamine-based plasmalogens (respectively -78 and - 73%, p < 0.0001), phosphatidylcholine-based plasmalogens (respectively - 44 and - 53%, p < 0.0001), d18: 1-sphingosine-1-phosphate (respectively - 52 and - 38%, p < 0.0001) and sphingomyelins (respectively - 19% (p < 0.0001) and -24% (p = 0.0006)), than did controls. Moreover, we observed a decrease in C18: 2 fatty acid-containing phospholipids and an increase in C20: 4 fatty acid-containing phospholipids.Conclusion: The sphingophospholipidome of HDL from normoglycaemic obese patients with metabolic syndrome is profoundly modified, before the dysregulation of glycaemia. Most of the changes observed have pejorative effect in terms of vascular protection. (C) 2015 Elsevier Ireland Ltd. All rights reserved