Macro vitamin B12: an underestimated threat.

Background The correct identification of the macro-B12 interference (macroforms) is paramount to avoid potential erroneous clinical decisions. Our objectives were to determine whether immunoassays are affected by the presence of macro-B12 and to validate a polyethylene glycol (PEG) precipitation procedure to detect it. Methods Sixty-two serum samples obtained from healthy volunteers were analyzed to determine recovery and reference intervals (RIs) following PEG precipitation. Thereafter, 50 serum samples with very high levels of B12 (>1476 pmol/L) were randomly selected to search for macro-B12 interferences. Serum samples obtained from healthy volunteers and related PEG aliquots were analyzed on a Cobas® immunoassay. Patients' samples were analyzed on both Cobas® and Architect® immunoassays. Finally, samples suspected to contain macro-B12 were analyzed by size-exclusion chromatography (SEC) to confirm the presence of macro-B12. Results Recovery and post-PEG RIs determined on a Cobas 8000® in healthy volunteers ranged from 68.3% to 108.4% and from 122.1 to 514.4 pmol/L, respectively. Fifteen samples (30%) were found to show macro-B12 while using the recovery criteria, and nine samples (18%) while using the post-PEG RI. The other immunoassay ran on the Architect i2000® was also affected by the presence of macro-B12. Size-exclusion chromatography studies confirmed the presence of macro-B12 (immunoglobulin-B12 complexes). Conclusions The prevalence of macro-B12 in elevated B12 samples is high. We suggest to systematically screen for the presence of macro-B12 with PEG precipitation procedure in samples with elevated B12 levels to avoid potential misdiagnosis or harmful clinical consequences.

Extremely broadband ultralight thermally-emissive optical coatings.

We report the design, fabrication, and characterization of ultralight highly emissive structures with a record-low mass per area that emit thermal radiation efficiently over a broad spectral (2 to 30 microns) and angular (0-60°) range. The structures comprise one to three pairs of alternating metallic and dielectric thin films and have measured effective 300 K hemispherical emissivity of 0.7 to 0.9 (inferred from angular measurements which cover a bandwidth corresponding to 88% of 300K blackbody power). To our knowledge, these micron-scale-thickness structures, are the lightest reported optical coatings with comparable infrared emissivity. The superior optical properties, together with their mechanical flexibility, low outgassing, and low areal mass, suggest that these coatings are candidates for thermal management in applications demanding of ultralight flexible structures, including aerospace applications, ultralight photovoltaics, lightweight flexible electronics, and textiles for thermal insulation.

Double trouble: Unmasking two hook effects on Siemens Atellica® - Total PSA and total hCG assays.

The "hook effect" or "prozone phenomenon" occurs when the concentration of a particular analyte saturates the antibodies used in the test, resulting in falsely low or negative results despite the presence of high analyte concentrations. We report two recent cases of hook effect encountered with a widely used immunoassay analyzer, the Siemens Atellica® IM1600. The first case involves a patient with advanced metastatic prostate cancer whose total PSA (tPSA) concentration dropped dramatically from his last biological control. The second case concerns a pregnant woman whose total HCG (ThCG) levels were also subject to the hook effect and who was found to have a molar pregnancy. In both cases, a dilution step enabled to overcome this analytical concern and to obtain a correct result. In addition, a comparison of the sensitivity of different immunoassay analyzers to this phenomenon was carried out. To avoid this analytical error, an additional dilution step should automatically be performed when there is a clinical suspicion of elevated levels of tumor or hormone markers. Finally, the most affected manufacturers should adapt their assays, accordingly.

Confounding Factors Influencing the Kinetics and Magnitude of Serological Response Following Administration of BNT162b2.

BACKGROUND: Little is known about potential confounding factors influencing the humoral response in individuals having received the BNT162b2 vaccine. METHODS: Blood samples from 231 subjects were collected before and 14, 28, and 42 days following coronavirus disease 2019 (COVID-19) vaccination with BNT162b2. Anti-spike receptor-binding-domain protein (anti-Spike/RBD) immunoglobulin G (IgG) antibodies were measured at each time-point. Impact of age, sex, childbearing age status, hormonal therapy, blood group, body mass index and past-history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were assessed by multivariable analyses. RESULTS AND CONCLUSIONS: In naïve subjects, the level of anti-Spike/RBD antibodies gradually increased following administration of the first dose to reach the maximal response at day 28 and then plateauing at day 42. In vaccinated subjects with previous SARS-CoV-2 infection, the plateau was reached sooner (i.e., at day 14). In the naïve population, age had a significant negative impact on anti-Spike/RBD titers at days 14 and 28 while lower levels were observed for males at day 42, when corrected for other confounding factors. Body mass index (BMI) as well as B and AB blood groups had a significant impact in various subgroups on the early response at day 14 but no longer after. No significant confounding factors were highlighted in the previously infected group.

Antibody titres decline 3-month post-vaccination with BNT162b2.

Several studies reported on the humoral response in subjects having received the BNT162b2 mRNA COVID-19 vaccine. However, data on the kinetics of antibodies 3 months post-vaccination are currently lacking and are important to drive the future vaccination strategy. The CRO-VAX HCP study is an ongoing multicentre, prospective and interventional study designed to assess the antibody response in a population of healthcare professionals who had received two doses of the BNT162b2 mRNA COVID-19 vaccine. Two hundred individuals underwent a blood drawn within 2 days before the first vaccine dose. One-hundred and forty-two persons (71%) were categorized as seronegative at baseline while 58 (29%) were seropositive. Samples were then collected after 14, 28, 42, 56, and 90 days. Antibodies against the SARS-CoV-2 nucleocapsid and the receptor binding domain of the S1 subunit of the spike protein were measured in all individuals at different time points. Using a one-compartment kinetics model, the time to maximum concentration was estimated at 36 ± 3 days after the first dose and the estimated half-life of antibodies was 55 days (95% CI: 37-107 days) in seronegative participants. In seropositive participants, the time to maximum concentration was estimated at 24 ± 4 days and the estimated half-life was 80 days (95% CI: 46-303 days). The antibody response was higher in seropositive compared to seronegative participants. In both seropositive and seronegative subjects, a significant antibody decline was observed at 3 months compared to the peak response. Nevertheless, the humoral response remained robust in all participants.

Waning of IgG, Total and Neutralizing Antibodies 6 Months Post-Vaccination with BNT162b2 in Healthcare Workers.

Data about the long-term duration of antibodies after SARS-CoV-2 vaccination are still scarce and are important to design vaccination strategies. In this study, 231 healthcare professionals received the two-dose regimen of BNT162b2. Of these, 158 were seronegative and 73 were seropositive at baseline. Samples were collected at several time points. The neutralizing antibodies (NAbs) and antibodies against the nucleocapsid and the spike protein of SARS-CoV-2 were measured. At day 180, a significant antibody decline was observed in seronegative (-55.4% with total antibody assay; -89.6% with IgG assay) and seropositive individuals (-74.8% with total antibody assay; -79.4% with IgG assay). The estimated half-life of IgG from the peak humoral response was 21 days (95% CI: 13-65) in seronegative and 53 days (95% CI: 40-79) in seropositive individuals. The estimated half-life of total antibodies was longer and ranged from 68 days (95% CI: 54-90) to 114 days (95% CI: 87-167) in seropositive and seronegative individuals, respectively. The decline of NAbs was more pronounced (-98.6%) and around 45% of the subjects tested were negative at day 180. Whether this decrease correlates with an equivalent drop in the clinical effectiveness against the virus would require appropriate clinical studies.

Biotin interferences: Have we neglected the impact on serological markers?

BACKGROUND: Biotin has been reported to be a leading cause of interference on several immunoassay platforms using the streptavidin-biotin immobilization system. While biotin interferences have now been well characterized for several assays, only few data are available on their impact on serological markers of infectious viral diseases. METHODS: Overall, 10 healthy volunteers (HVs) received a single 100 mg dose of biotin to evaluate its effect on hepatitis B serological markers. Blood samples were taken several times before and after biotin intake. In addition, spiking experiments were applied to investigate biotin's impact on anti-HIV/p24 Ag and anti-HCV antibody levels. Several procedures designed to overcome this interference were evaluated. RESULTS: Biotin intake resulted in a false-negative anti-HBs immunological status (<10 mIU/mL) in 40.0% of cases. According to our anti-HBc and anti-HBe results, biotin intake was associated with 90.0% and 80.0% of false positive results, respectively. At the theoretical biotin peak concentration following a 100 mg intake, 50.0% and 66.6% of anti-HIV and anti-HCV results were false negatives, respectively. All the procedures evaluated to overcome the interference were proven effective. CONCLUSION: HBV, HCV, and HIV serological markers are likely to be highly sensitive to biotin. Our data confirm that the scope of biotin interference is broader than commonly described.

FGF23: Clinical usefulness and analytical evolution.

Fibroblast Growth Factor 23 (FGF23) is a key hormone for the regulation of phosphate homeostasis. Over the past decades, FGF23 was the subject of intense research in the fields of nephrology and the cardiology. It presents a remarkable correlation with well-established biomarkers of cardiovascular disorders in both chronic kidney disease (CKD) and heart failure (HF) patients. The interest of FGF23 lies in its early-onset in the primary course of CKD as well as in the incremental prognosis information it conveys in both CKD and HF. Different types of assays of FGF-23 testing exist, those targeting the intact form (iFGF23), the other one detecting terminal fragments (cFGF23). The issue is still pending which assay suits best for clinical use. Recently, the implementation of this biomarker on multianalyzer platforms, on which other markers of phospho-calcic balance are set up, allows a rapid turn-around-time and a potential financial gain. However, despite the good analytical performances of the automated methods, there is a poor harmonization between assays. The introduction of an international certified reference material should standardize the measurement and improve the harmonization of results from different laboratories. A deeper understanding of physio-pathological mechanisms and processing of FGF-23 should reinforce its clinical indications and might also identify new therapeutic targets for the treatment of CKD and HF.

Primer Consenso Nacional Intersociedades de Inmunización del Adulto. 2023

Las vacunas previenen millones de muertes cada año y su eficacia y seguridad han sido ampliamente establecidas. En términos económicos, la vacunación es una de las intervenciones sanitarias más costo efectivas, generando un importante ahorro y crecimiento económico que supone a largo plazo. Se ha demostrado que la vacunación de adultos disminuye la morbilidad y la mortalidad asociadas a enfermedades infecciosas prevenibles, reduciendo las complicaciones y las hospitalizaciones, incluidos los ingresos a las unidades de cuidados intensivos. Hemos elaborado este documento de consenso con el objeto de diseñar un esquema de vacunación pragmático, accesible y estandarizado del adulto, según categoría de riesgo y edad, sobre la base de la evidencia disponible de vacunas accesibles y nuevas vacunas habiendo utilizado el Tercer Consenso de la Sociedad Paraguaya de Infectología del 2019 como base para las recomendaciones finales.

SUMMARY Vaccines prevent millions of deaths each year, and their efficacy and safety have been widely established. In economic terms, vaccination is one of the most cost-effective health interventions, generating significant savings and long-term economic growth. Adult vaccination has been shown to decrease morbidity and mortality associated with preventable Infectious diseases, reducing complications and hospitalizations, including admissions to intensive care units. We have prepared this consensus document in order to design a pragmatic, accessible and standardized vaccination scheme for adults, according to risk category and age, based on the available evidence of available vaccines and new vaccines, having used the third consensus of the Paraguayan Infectious Diseases Society of 2019 as a basis for the final recommendations.

Intervalo QTc prolongado en pacientes de Clínica Médica: estudio multicéntrico

RESUMEN Antecedentes: el síndrome de QT prolongado (SQTP) adquirido se asocia al uso de ciertos fármacos. La detección oportuna del SQTP permite tomar medidas para prevenir arritmias ventriculares potencialmente letales. Objetivo: determinar la frecuencia de SQTP en pacientes adultos internados en Servicios de Clínica Médica, describir las características demográficas, clínicas, laboratoriales y el uso de fármacos asociados con la prolongación del intervalo QTc. Materiales y métodos: se aplicó diseño observacional, prospectivo, longitudinal, en varones y mujeres, mayores de 16 años de edad, internados en el Servicio de Clínica Médica del Hospital Nacional (Itauguá, Paraguay) y del Hospital Militar Central (Asunción, Paraguay) en 2019. Se midieron variables demográficas, clínicas, laboratoriales y un electrocardiograma (ECG) al ingreso y a la semana de internación. Se consideró STQL todo valor del intervalo QTc ≥0,45 seg en hombres y ≥0,47 seg en mujeres. Resultados: ingresaron al estudio 257 sujetos, 55% varones y 45% mujeres, con edad media 58±20 años. Se detectó SQTP en 55 pacientes (21%). Los fármacos más utilizados en los pacientes con SQTP fueron omeprazol, furosemida, piracilina-tazobactam, tramadol, ondasentrón, amiodarona, salbutamol, ciprofloxacina, antirretrovirales, levofloxacina, metoclopramida y cotrimoxazol. Conclusión: la frecuencia de SQTP fue 21%. La comorbilidad más frecuente fue la hipertensión arterial (62%). Los fármacos más utilizados en los pacientes con SQTP fueron los de uso común en las salas de Clínica Médica.

ABSTRACT Background: Acquired prolonged QT syndrome (SQTP) is associated with the use of certain drugs. Timely detection of SQTP allows measures to be taken to prevent potentially lethal ventricular arrhythmias. Objective: To determine the frequency of SQTP in adult patients admitted to Clinical Medicine Services, to describe the demographic, clinical, laboratory characteristics and the use of drugs associated with prolongation of the QTc interval. Materials and methods: Observational, prospective, longitudinal design was applied in men and women, over 16 years of age, admitted to the Clinical Medicine Service of the National Hospital (Itauguá, Paraguay) and the Central Military Hospital (Asunción, Paraguay) in 2019. Demographic, clinical, laboratory variables and an electrocardiogram (ECG) were measured at admission and at one week of hospitalization. All values ​​of the QTc interval ≥0.45 sec in men and ≥0.47 sec in women were considered STQL. Results: Two hundred fifty-seven subjects, 55% men and 45% women, with a mean age of 58±20 years, entered the study. SQTP was detected in 55 patients (21%) while the most commonly used drugs in patients with SQTP were omeprazole, furosemide, piperacillin-tazobactam, tramadol, ondansetron, amiodarone, salbutamol, ciprofloxacin, antiretroviral drugs, levofloxacin, metoclopramide and cotrimoxazole. Conclusion: The frequency of SQTP was 21% and the most frequent comorbidity was arterial hypertension (62%). The most commonly used drugs in patients with SQTP were those commonly used in the Clinical Medicine rooms.