Allergic reactions to COVID-19 vaccines: statement of the Belgian Society for Allergy and Clinical Immunology (BelSACI).

Vaccination against COVID-19 constitutes a huge hope and a major challenge. For the first time in modern history, a global vaccination campaign has started worldwide in a short period of time and with products that were recently developed. Consequently, legitimate concerns regarding the safety and tolerability of COVID-19 vaccines arise.In line with international allergy societies, the Belgian Society for Allergy and Clinical Immunology (BelSACI) provides this statement to guide health care providers (general practitioners, specialists including allergists) and stakeholders.In this statement, we first review current evidence on allergic reactions to vaccines and the potential risk factors that have been identified.Second, we provide a risk stratification method that may be used as a worksheet during the vaccination campaign.Finally, we discuss the management of suspected or confirmed allergic reactions following vaccination.

Meeting report of the "Symposium on kidney stones and mineral metabolism: calcium kidney stones in 2017".

A symposium on kidney stones and mineral metabolism held on December 2017 in Brussels, Belgium was the first international multidisciplinary conference of the International Collaborative Network on Kidney Stones and Mineral Metabolism. This meeting addressed epidemiology, underlying pathophysiological mechanisms, genetics, pathological, as well as clinical and research topics. The participants included clinicians and recognized experts in the field from Europe and the United States interacted closely during the symposium which promoted a chance to explore new frontiers in the field of kidney stone disease. This manuscript summarizes some of the major highlights of the meeting.

Clinical data on rare Sulfamethoxazole crystalluria assessed by Fourier transform infrared spectrophotometry.

The data contained in this article are related to the article entitled "Case report: Uncommon Sulfamethoxazole Crystalluria" (Castiglione et al., 2018). Sulfamethoxazole crystalluria is very rare and crystals identification is complex (de Liso et al., 2016). We identified seven patients with uncommon urine crystals that were composed of N-Acetyl-Sulfamethoxazole. Three of the patients developed an acute renal failure simultaneously to crystalluria. Hence, this data article describes the method of crystals identification thanks to infrared spectroscopy. The relevant clinical data of patients, including medical history, drug dosage and urine parameters related to the crystalluria are presented.

Raman chemical imaging, a new tool in kidney stone structure analysis: Case-study and comparison to Fourier Transform Infrared spectroscopy.

BACKGROUND AND OBJECTIVES: The kidney stone's structure might provide clinical information in addition to the stone composition. The Raman chemical imaging is a technology used for the production of two-dimension maps of the constituents' distribution in samples. We aimed at determining the use of Raman chemical imaging in urinary stone analysis. MATERIAL AND METHODS: Fourteen calculi were analyzed by Raman chemical imaging using a confocal Raman microspectrophotometer. They were selected according to their heterogeneous composition and morphology. Raman chemical imaging was performed on the whole section of stones. Once acquired, the data were baseline corrected and analyzed by MCR-ALS. Results were then compared to the spectra obtained by Fourier Transform Infrared spectroscopy. RESULTS: Raman chemical imaging succeeded in identifying almost all the chemical components of each sample, including monohydrate and dihydrate calcium oxalate, anhydrous and dihydrate uric acid, apatite, struvite, brushite, and rare chemicals like whitlockite, ammonium urate and drugs. However, proteins couldn't be detected because of the huge autofluorescence background and the small concentration of these poor Raman scatterers. Carbapatite and calcium oxalate were correctly detected even when they represented less than 5 percent of the whole stones. Moreover, Raman chemical imaging provided the distribution of components within the stones: nuclei were accurately identified, as well as thin layers of other components. Conversion of dihydrate to monohydrate calcium oxalate was correctly observed in the centre of one sample. The calcium oxalate monohydrate had different Raman spectra according to its localization. CONCLUSION: Raman chemical imaging showed a good accuracy in comparison with infrared spectroscopy in identifying components of kidney stones. This analysis was also useful in determining the organization of components within stones, which help locating constituents in low quantity, such as nuclei. However, this analysis is time-consuming, making it more suitable for research studies rather than routine analysis.

[Epidemiology of urolithiasis in Belgium on the basis of a morpho-constitutional classification]. / Épidémiologie de la lithiase urinaire en Belgique sur base d'une classification morpho-constitutionnelle.

Urolithiasis is a common condition, with a prevalence of ∼10% and a male/female ratio above 1 according to large national series. Various types of urinary stones have been described upon their mineral content and/or their morphology. Hence, a combined morpho-constitutional (M-C) classification has been proposed. In order to detail the prevalence of urolithiasis in general and of each M-C type in particular upon age and gender in Belgium, we retrospectively studied the database of a reference center for urolithiasis analysis. Between 2010 and 2013, 2195 stones were characterized. We excluded 45 non-biological stones and 281 stones, which originated from outside the study zone. Among 1869 stones, 1293 (69.2%) affected men. Prevalence peak of urolithiasis was observed between 50-60 years of age in both genders. The M-C analysis was available for 1854 stones (99.2%): multiple morphological types were concomitantly identified in 49.3%. In the whole population, the main mineral constituent was whewellite (54.4%), mainly organized as type Ia (94%). Weddellite was found in 19.8%, with an equal distribution between types IIa and IIb. Uric acid was the 3rd most frequent constituent in man, with a similar distribution between IIIa and IIIb. Phosphate was uncommon in man (8.2%), but frequent in woman (26.6%) with a type IVa1 organization. Prevalence of M-C types changes with aging, i.e. decrease of weddellite and increase of whewellite and uric acid in both genders. This retrospective analysis of a single-center database of urinary stones helps characterize the M-C epidemiology of urolithiasis in Belgium.

Vitamin D status after a high dose of cholecalciferol in healthy and burn subjects.

BACKGROUND: Burn patients are at risk of vitamin D (VD) deficiency and may benefit from its pleiotropic effects as soon as acute phase. Aim of this observational study was to assess effects of a cholecalciferol (VD3) bolus on VD status in adult burn patients (Group B, GB) after admission, compared to healthy subjects (Group H, GH). METHODS: Both groups received an oral dose of 100,000 IU VD3. Blood samples were collected before (D0) and 7 days (D7) after bolus to measure 250H-D, 1,25(OH)2-D, parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23). Albumin (ALB) and VD binding protein (DBP) were measured and used to calculate free 25OH-D level. Data were expressed as median (min-max) or proportions. RESULTS: A total of 49 subjects were included: 29 in GH and 20 in GB. At D0, prevalence of VD deficiency was higher in GB: 25OH-D was 21.5 (10.1-46.3) ng/ml in GH vs 11 (1.8-31.4) ng/ml in GB. DBP and ALB were lower in GB. At D7, DBP was stable in both groups while ALB decreased in GB. 25OH-D increased by 66.6 (13.5-260.3)% in GH. In GB, changes in 25OH-D extended from -36.7% to 333.3% with a median increase of 33.1%. Similar changes were observed in each group for free 25OH-D. High FGF23 levels were observed in GB. CONCLUSIONS: This study highlighted the differences in VD status and in response to a high dose VD3 in burn patients when compared to healthy patients. Pitfalls in VD status assessment are numerous during acute burn care: 25OH-D measurement needs cautious interpretation and interest of free 25OH-D is still questionable. They should not prevent burn patients to receive VD supplements during acute care. Higher doses than general recommendations should probably be considered.

Critical care and vitamin D status assessment: what about immunoassays and calculated free 25OH-D?

BACKGROUND: Interpretation of 25OH-D measurement during critical care (CC) may be problematic due to variations of binding protein concentrations (albumin, ALB, and vitamin D binding protein, VDBP). Determination of free 25OH-D concentration may thus be relevant in CC patients. The aim of this observational study was to evaluate effects of an acute hemodilution on vitamin D (VD) status. METHODS: Blood samples were obtained before (T1) and after a crystalloid load (T2) administered at anesthesia induction for minor surgery. 25OH-D was measured with LC-MS/MS and with 3 immunoassays (IA): DiaSorin Liaison, IDS iSYS and bioMérieux Vidas. VDBP was measured with the R&D Elisa and ALB on Cobas. Free 25OH-D was calculated using published formula. Accuracy of each 25OH-D IA was calculated as the percentage of IA values within 20% of their respective LC-MS/MS values. Performances of the three AI were compared with LC-MC/MS using Bland-Altman analysis. RESULTS: Twenty adults were included. Compared to T1 values, VDBP, ALB and LC-MS/MS values decreased in parallel by a mean of 23% at T2. IA values decreased less significantly (12, 14 and 15% for Liaison, iSYS and Vidas, respectively). IA-based calculated free 25OH-D significantly increased after dilution, while LC-MS/MS-based free values remained stable. At T1 and T2, bias were demonstrable for all IA. After hemodilution, bias would lead to overestimation for the three IA. Accuracy of IA decreased after dilution. CONCLUSIONS: Due to matrix effects, compared to LC-MS/MS, IA results were impacted by hemodilution. In CC patients, LC-MS/MS seems to be the best option to measure 25OH-D. Specific LC-MS/MS method should be developed to measure free 25OH-D.

Inter-method variability in bone alkaline phosphatase measurement: clinical impact on the management of dialysis patients.

BACKGROUND: Bone-specific alkaline phosphatase (BAP) is now recommended to assess bone turnover in hemodialysis (HD) patients. However, little is known about potential variability between methods available to measure BAP. METHODS: We measured BAP in 76 HD patients with six different assays (Beckman-Coulter Ostase IRMA, Beckman-Coulter Ostase Access, IDS iSYS Ostase, IDS Ostase enzyme immunoassay, DiaSorin Liaison Ostase and Quidel MicroVue BAP). RESULTS: We observed a high correlation between all the assays ranging from 0.9948 (IDS iSYS vs. IDS EIA) to 0.9215 (DiaSorin Liaison vs. Quidel MicroVue). However, using the regression equations, the equivalent concentration of a Beckman-Coulter Access value of 10 µg/L can range from 7.7 to 14.4 µg/L and of 20 µg/L can range from 16.9 to 27.9 µg/L with other assays. According to Beckman-Coulter Access, 13%, 50% and 37% of the patients presented BAP values ≤10, between 10 and 20 and ≥20 µg/L, respectively. Discrepancies are observed when other assays are used (concordance from 10 to 100%). CONCLUSIONS: Analytical problems leading to inter-method variation should be overcome to improve the usefulness of this marker in clinical practice. According to correlation results, recalibration of BAP assays is necessary but should not be a major issue.

Standardization of DiaSorin and Roche automated third generation PTH assays with an International Standard: impact on clinical populations.

BACKGROUND: Standardization of parathyroid hormone (PTH) assays is a major issue, especially in hemodialyzed (HD) patients. Two automated third generation PTH assays (Roche Elecsys and DiaSorin Liaison) are now available. These assays are specific for the (1-84) PTH and do not cross-react with the (7-84) fragment, contrary to second generation (intact) assays. We aimed to calibrate the two methods against the WHO International PTH Standard (IS) 95/646 to see if the two assays could provide comparable results in a population of healthy subjects, HD patients and patients suffering from primary hyperparathyroidism (PHP). METHODS: We selected 79 healthy subjects and two populations of patients presenting PTH disorders: 56 HD and 27 PHP patients. We reconstituted the IS in a pool of human serum containing undetectable levels of 1-84 PTH and prepared 13 serum standards ranging from 0 to 2000 pg/mL. The standards were run on the two instruments to calibrate the assays on the IS. The different populations were run before and after restandardization. RESULTS: As these kits were differently calibrated, the results obtained after restandarization were significantly different. Restandardization process improved concordance between assays and, taking the analytical variability of the two kits into account, the results could be considered to be similar. CONCLUSIONS: Restandardization of automated third generation PTH assays with the WHO 1-84 PTH Standard significantly reduces inter-method variability. Reference ranges and raw values are totally transposable from one method to the other in healthy subjects, but also in diseased patients, e.g., with HD or those suffering from PHP.

Evaluation of automated immunoassays for 25(OH)-vitamin D determination in different critical populations before and after standardization of the assays.

INTRODUCTION: Standardization of immunoassays for 25(OH)-vitamin D determination is a major problem in clinical practice. A worldwide standardization program has started to address this and will reduce the bias observed between immunoassays. We aimed to calibrate 5 immunoassays on a LC-MS/MS traceable to the SRM 2972 and the ID-LC-MS/MS 25(OH)D Reference Method Procedure to see if the re-standardization would be efficient in a population of 3rd trimester pregnant women (PW), hemodialysis (HD) and osteoporosis (OP) patient. MATERIAL AND METHODS: 184 serum samples (25(OH)D: 8.4-87 ng/ml) were selected to calibrate the immunoassays (Abbott-Architect, Roche-Elecsys, DiaSorin-Liaison, Siemens-Centaur and IDS-iSYS). Chromsystems MassChrom method was used as the referenced. Serum obtained in 34 PW, 25 HD and 34 OP patients were used as comparatives. RESULTS: After adjusting to LC-MS/MS, immunoassays had regression slopes nearly identical to 1.0 with intercepts <0.5 ng/ml. However, in special populations, a systematic bias was still observed, except for iSYS. CONCLUSIONS: Re-standardization of 25(OH)D immunoassay will globally improve the differences. However, patients with a different serum matrix will still present significantly different results when they will be run with different methods. For those patients, the LC-MS/MS method seems to be the method of choice, even if some immunoassays are less influenced than others.

The third/second generation PTH assay ratio as a marker for parathyroid carcinoma: evaluation using an automated platform.

BACKGROUND: Parathyroid carcinoma (PCa) is rare and often difficult to differentiate initially from benign disease. Because PCa oversecretes amino PTH that is detected by third-generation but not by second-generation PTH assays, the normal 3rd/2nd generation PTH ratio (<1) is inverted in PCa (ie, >1). OBJECTIVE: The objective of the investigation was to study the utility and advantages of automated 3rd/2nd generation PTH ratio measurements using the Liaison XL platform over existing manual techniques. SETTING: The study was conducted at a tertiary-referral academic center. DESIGN: This was a retrospective laboratory study. SUBJECTS: Eleven patients with advanced PCa (mean age 56.0 y). The controls were patients with primary-hyperparathyroidism (n = 144; mean age 53.8 y), renal transplantation (n = 41; mean age 50.6 y), hemodialysis (n = 80; mean age 65.2 y), and healthy elderly subjects (n = 40; mean age 72.6 y). RESULTS: The median (interquartile range) 3rd/2nd generation PTH ratio was 1.16 (1.10-1.38) in the PCa group, which was significantly higher than the control groups: hemodialysis: 0.74 (0.71-0.75); renal transplant: 0.77 (0.73-0.79); primary hyperparathyroidism: 0.76 (0.74-0.78); healthy elderly: 0.80 (0.74-0.83). An inverted 3rd/2nd-generation PTH ratio (>1) was seen in 9 of 11 PCa patients (81.8%) and in 7 of 305 controls (2.3%): 3 of 80 hemodialysis (3.8%), and 4 of 144 primary-hyperparathyroidism patients (2.8%). Of four PCa patients who had a normal PTH ratio with the manual method, two had an inverted 3rd/2nd-generation PTH ratio with the automated method. CONCLUSIONS: Study of the 3rd/2nd-generation PTH ratio in large patient populations should be feasible using a mainstream automated platform like the Liaison XL. The current study confirms the utility of the inverted 3rd/2nd-generation PTH ratio as a marker of PCa (sensitivity: 81.8%; specificity: 97.3%).

Multicentre evaluation of a second generation point-of-care assay with an extended range for the determination of N-terminal pro-brain natriuretic peptide.

BACKGROUND: In the second generation of the point-of-care (POC) assay Roche CARDIAC proBNP, the upper limit of the measuring range was extended from 3000 to 9000 ng/L. METHODS: A thirteen-site multicentre evaluation was carried out to assess the analytical performance of the POC NT-proBNP assay and to compare it with a laboratory N-terminal pro-brain natriuretic peptide (NT-proBNP) assay. RESULTS: In method comparisons of six lots of POC NT-proBNP with the lab reference method (Elecsys proBNP) mean bias ranged from -10 to +17%. In lot-to-lot comparisons all six investigated lots of POC NT-proBNP showed excellent agreement, with mean bias between -7% and +2%. The majority of all coefficients of variation obtained from ten-fold measurements using 56 native blood samples were below 8%. No interference was observed with hemolytic blood (hemoglobin concentrations up to 0.12 mmol/L), lipemic blood (triglyceride concentrations up to 14.0 mmol/L) nor icteric blood (bilirubin concentrations up to 63 micromol/L). Hematocrit values between 24% and 51% had no influence on the assay result. High NT-proBNP concentrations above the measuring range of POC NT-proBNP did not lead to false low results due to potential high-dose hook effect. Results with POC NT-proBNP were not influenced by different ambient temperatures (18 degrees C to 32 degrees C), the sample material used, nor by over- or underdosing by 15 microL compared to the regular sample volume of 150 microL. CONCLUSIONS: The POC NT-proBNP assay showed an excellent analytical performance including a good agreement with the laboratory method. The assay is therefore suitable for its intended use in point-of-care settings.

Secondary soy allergy in children with birch pollen allergy may cause both chronic and acute symptoms.

BACKGROUND: Secondary soy allergy occurring in tree pollen allergic patients may cause acute symptoms. METHODS: We selected children with birch pollen allergy suspected of also being soy allergic (SA). Soy allergy was proven based on one of the following: (i) a clear-cut clinical history; (ii) a positive provocation test; and (iii) elimination and reintroduction of soy. Skin prick tests (SPT) were performed with a commercial soy extract and with soy flour. Specific IgE to Gly m 4, Gly m 5, and Gly m 6 was determined by means of ImmunoCAP and ISAC. Eight soy-tolerant atopic children being CAP rGly m 4-negative served as a control group for skin testing. RESULTS: Of 15 subjects with birch pollen allergy and being suspected of soy allergy, eight of them proved to be SA; 7/15 subjects proved to be soy tolerant (ST). Besides acute symptoms in 8/8 SA subjects, 3/8 subjects also had been suffering from severe chronic complaints because of soy allergy. SPT with commercial soy extract was negative in all SA and ST subjects tested. SPT with soy flour was positive in 8/8 SA and in 5/6 ST subjects, but negative in all 8 controls (p < 0.0001); the median weal diameter was 7.7 mm in SA subjects, compared to 3 mm in ST subjects (p < 0.01). The median IgE level to rGly m 4 using CAP and ISAC was, respectively, 32.4 kU/l and 4.0 ISU in SA subjects, compared to 6.2 kU/l and 0.4 ISU in ST subjects (p < 0.05). Analysis of IgE to nGly m 5 and nGly m 6, using CAP or ISAC, showed no significant differences between SA and ST subjects. CONCLUSIONS: Secondary soy allergy may cause severe chronic besides acute symptoms. SPT with soy flour is a sensitive and specific tool in detecting soy sensitization. SPT with soy flour, CAP rGly m 4, and ISAC rGLY m 4 are valuable tools in the diagnosis of birch-pollen-associated secondary soy allergy.

A new tool in the field of in-vitro diagnosis of allergy: preliminary results in the comparison of ImmunoCAP© 250 with the ImmunoCAP© ISAC.

BACKGROUND: The ImmunoCAP© ISAC allows for the determination of specific immunoglobulin E (IgE) against 103 recombinant or purified allergen components in a single analytical step. The aim of our study was to perform a comparison of the specific IgE results measured with the microarray method to those obtained using the traditional method of ImmunoCAP©. METHODS: We selected 86 clinically relevant patients on the basis of their specific IgE for recombinant allergens (ImmunoCAP© 250, Phadia). Also, we selected two patients with a high total IgE to evaluate the non-specific binding of IgE. All samples were screened with the ImmunoCAP© ISAC. Then, we compared the 555 specific IgE antibodies results provided by ImmunoCAP© ISAC with the specific IgE levels obtained with ImmunoCAP© 250. RESULTS: We observed that 82 of the 384 results found to be positive with ImmunoCAP© were negative with ISAC© (concordance 78.65%). Of 171 negative results obtained with ImmunoCAP©, 11 were positive with ISAC© (concordance 93.57%). No non-specific binding was observed. CONCLUSIONS: Our results show that the ImmunoCAP© ISAC has good analytical performance when compared with the ImmunoCAP© 250 method. We did not observe any non-specific binding. However, better sensitivity for some clinically relevant allergen components, such as rPru p 3 is needed.