The role of C-reactive protein and ferritin in the diagnosis of HLH, adult-onset still's disease, and COVID-19 cytokine storm.

Cytokine storm syndromes such as hemophagocytic lymphohistiocytosis (HLH), Adult-onset Still's disease (AOSD), and COVID-19 cytokine storm (CCS) are characterized by markedly elevated inflammatory cytokines. However clinical measurement of serum cytokines is not widely available. This study examined the clinical utility of C-reactive protein (CRP) and ferritin, two inexpensive and widely available inflammatory markers, for distinguishing HLH from AOSD and CCS.

CRP and sCD25 help distinguish between adult-onset Still's disease and HLH.

Objective: Adult-onset Still's disease (AOSD) and secondary hemophagocytic lymphohistiocytosis (sHLH) are both hyperferritinemic cytokine storm syndromes that can be difficult to distinguish from each other in hospitalized patients. The objective of this study was to compare the inflammatory markers ferritin, D-dimer, C-reactive protein (CRP), and soluble CD25 (sCD25) in patients with AOSD and sHLH. These four markers were chosen as they are widely available and represent different aspects of inflammatory diseases: macrophage activation (ferritin); endothelialopathy (D-dimer); interleukin-1/interleukin-6/tumour necrosis factor elevation (CRP) and T cell activation (sCD25).

Molecular confirmation of alpha 1-antitrypsin deficiency in liver transplant setting: A province-wide experience.

Background And Aim: Patients suspected of Alpha 1-Antitrypsin (A1AT) abnormality based on low serum concentration are routinely confirmed through polymerase chain reaction (PCR) testing of peripheral blood. Genotyping formalin-fixed paraffin-embedded (FFPE) tissue is a novel approach that could aid in detecting variant A1AT. We performed qPCR on FFPE liver explants with Periodic Acid Schiff after Diastase (PASD)- and A1AT-positive globules to confirm and estimate the frequency of A1AT deficiency in transplant cases.

Mass spectrometry in IgG4-related disease diagnosis.

We compared liquid chromatography tandem mass spectrometry (LC-MS/MS) against Binding Site immunonephelometry (BSIN) with regards to these methods' abilities to diagnose IgG4-related disease (IgG4-RD). IgG subclasses were gathered from laboratory from December 2011 to December 2020. The IgG4-RD positive and negative patients were diagnosed according to the ACR/EULAR classification criteria by extensive chart review.

Macrocytosis in Mitochondrial DNA Deletion Syndromes.

Large single mitochondrial DNA (mtDNA) deletion syndrome is a rare inborn error of metabolism with variable heteroplasmy levels and clinical phenotype among affected individuals. Chronic progressive external ophthalmoplegia (CPEO) is the most common phenotype in adults with this form of mitochondrial disease [J Intern Med. 2020;287(6):592-608 and Biomed Rep.

Quantitation of IgG Subclasses in Serum Using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS).

Serum IgG subclasses (IgGSC) are measured for a number of indications, but the most common are the identification of selective immunodeficiency disease and the diagnosis of IgG4-related disease (IgG4RD). Traditional nephelometric (IN) assays can suffer from two issues impacting the accuracy of the results: (1) hook effect and (2) antibody cross-reactivity between the subclasses. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is not vulnerable to these modes of interference and therefore serves as an excellent and relatively inexpensive means of diagnosing and/or monitoring the relevant clinical conditions.

The impact of IgG subclass deficiency on the risk of mortality in hospitalized patients with COPD.

Background: Immunoglobulin G (IgG) deficiency increases the risk of acute exacerbations and mortality in chronic obstructive pulmonary disease (COPD). However, the impact of IgG subclass deficiency on mortality in COPD is unknown. Here, we determined which IgG subclass, if any, is associated with increased risk of mortality in COPD.

Clinical interpretation of serum hepcidin-25 in inflammation and renal dysfunction.

Introduction: Hepcidin is a hormone that regulates systemic iron homeostasis. Serum hepcidin levels are under the influence of various stimuli, particularly inflammation and renal dysfunction. The measurement of hepcidin in circulation is a potentially useful clinical tool in the diagnosis, monitoring and treatment of iron metabolism disorder, although clinical interpretation of hepcidin level remains difficult.

Is the diagnostic rate for the common subtypes of A1AT deficiency consistent across two Canadian Provinces?

Background: The diagnosis of alpha-1-antitrypsin (A1AT) deficiency has been hindered by obscurity concerning the testing process and treatment implications. In this study, we aimed to identify regional differences in the diagnostic rates for A1AT deficiency in the western Canadian provinces of British Columbia (BC) and Alberta (AB).

Methods: The number of A1AT deficiency variant genotype (ZZ, SZ, MZ, SS, and MS) diagnoses were reviewed for BC and AB.

Polyclonal hypergammaglobulinaemia: assessment, clinical interpretation, and management.

This Review outlines a practical approach to assessing and managing polyclonal hypergammaglobulinaemia in adults. Polyclonal hypergammaglobulinaemia is most commonly caused by liver disease, immune dysregulation, or inflammation, but can also provide an important diagnostic clue of rare diseases such as histiocyte disorders, autoimmune lymphoproliferative syndrome, Castleman disease, and IgG4-related disease. Causes of polyclonal hypergammaglobulinaemia can be divided into eight categories: liver disease, autoimmune disease and vasculitis, infection and inflammation, non-haematological malignancy, haematological disorders, IgG4-related disease, immunodeficiency syndromes, and iatrogenic (from immunoglobulin therapy).

Maternal vitamin B status in early pregnancy and its association with birth outcomes in Canadian mother-newborn Dyads.

Vitamin B12 (B12) is a co-enzyme essential for fetal growth and development. Lower maternal B12 status has been associated with preterm birth (<37 gestational weeks) and low birth weight (<2500 g), which are linked to morbidity and mortality across the lifespan. In Canada, 17-25 % of women in early pregnancy had a serum total B12 concentration <148 pmol/l and maternal total B12 concentration decreased throughout pregnancy.

Falsely elevated serum estradiol due to heterophile antibody interference: a case report.

Falsely elevated estradiol is rare, may result from heterophile antibody interference, and can result in unnecessary investigation and intervention. We present the case of a 56-year-old female with falsely elevated estradiol levels inconsistent with her overall clinical picture, which ultimately led to an unnecessary surgical procedure. With the use of alternative analytical platforms and a heterophile antibody blocking agent, we determined the false elevation was due to heterophile antibody interference.

Incidental alpha-1-antitrypsin deficiency found in post-transplant liver allografts: Report of two cases.

Alpha-1 antitrypsin deficiency is an autosomal recessive disease most commonly caused by misfolding of the Alpha-1-antitrypsin protein, which prevents its release from hepatocytes into the systemic circulation. This results in increased lifetime risk of liver and lung disease. Due to its variable penetrance, presentation and natural history, patients with alpha-1 antitrypsin deficiency are often underdiagnosed.

Lactate and glucose as additional considerations to the plasma sodium level-corrected erythrocyte mean corpuscular volume report when using the Sysmex XE-2100.

Background: Mean corpuscular volume (MCV) can be artefactually inflated, by variation in sodium concentration, on the Sysmex XE-2100. We report that severe hyperglycemia and modest lactic acidemia can also spuriously increase MCV. To catch and correct such inaccurate MCV measurements, we propose to flag them using commonly assayed biomarkers.

Performance of StatSensor Point-of-Care Device for Measuring Creatinine in Patients With Chronic Kidney Disease and Postkidney Transplantation.

Background: The StatSensor is a point-of-care device which measures creatinine in capillary whole blood. Previous studies reported an underestimation of the creatinine measurements at high creatinine concentrations and were performed in the prestandardization era for creatinine.

Objective: This accuracy-based study evaluates the use of this device in kidney-transplanted patients and those with chronic kidney disease (CKD).