Poor Mobilization-Associated Factors in Autologous Hematopoietic Stem Cell Harvest.

Peripheral blood stem cell transplantation (PBSCT) is an important therapeutic measure for both hematologic and non-hematologic diseases. For PBSCT to be successful, sufficient CD34+ cells need to be mobilized and harvested. Although risk factors associated with poor mobilization in patients with hematologic diseases have been reported, studies of patients with non-hematologic diseases and those receiving plerixafor are rare. To identify factors associated with poor mobilization, data from autologous PBSC harvest (PBSCH) in 491 patients were retrospectively collected and analyzed. A multivariate analysis revealed that in patients with a hematologic disease, an age older than 60 years (odds ratio [OR] 1.655, 95% confidence interval [CI] 1.049-2.611, p = 0.008), the use of myelotoxic agents (OR 4.384, 95% CI 2.681-7.168, p < 0.001), and a low platelet count (OR 2.106, 95% CI 1.205-3.682, p = 0.009) were associated with poor mobilization. In patients with non-hematologic diseases, a history of radiation on the pelvis/spine was the sole associated factor (OR 12.200, 95% CI 1.934-76.956, p = 0.008). Among the group of patients who received plerixafor, poor mobilization was observed in 19 patients (19/134, 14.2%) and a difference in the mobilization regimen was noted among the good mobilization group. These results show that the risk factors for poor mobilization in patients with non-hematologic diseases and those receiving plerixafor differ from those in patients with hematologic diseases; as such, non-hematologic patients require special consideration to enable successful PBSCH.

CEBPA double mutations associated with ABO antigen weakness in hematologic diseases.

ABSTRACT: ABO antigen weakness is rarely observed in ABO typing for transfusion. Hematologic diseases and associated gene mutations have been suggested as potential causes of this phenomenon, yet the precise etiology has not been elucidated. Through ABO typing and genetic analysis data conducted over 7 years, we have reconfirmed the association between ABO antigen weakness and hematologic diseases, especially acute myeloid leukemia (odds ratio [OR], 2.55; 95% confidence interval [CI], 1.12-5.83) and myelodysplastic syndrome (OR, 6.94; 95% CI, 2.86-16.83), and discovered previously unidentified candidate genes, CEBPA (OR, 43.70; 95% CI, 18.12-105.40), NRAS (OR, 3.37; 95% CI, 1.46-7.79), U2AF1 (OR, 8.12; 95% CI, 2.86-23.03), and PTPN11 (OR, 4.52; 95% CI, 1.51-13.50), seemingly associated with this phenomenon. Among these, CEBPA double mutations displayed a significant association, with ABO antigen weakness being observed in 20 of the 25 individuals (80.0%) possessing these mutations. From this study, new factors associated with ABO antigen weakness have been identified.

Synergistic toxicity with copper contributes to NAT2-associated isoniazid toxicity.

Anti-tuberculosis (AT) medications, including isoniazid (INH), can cause drug-induced liver injury (DILI), but the underlying mechanism remains unclear. In this study, we aimed to identify genetic factors that may increase the susceptibility of individuals to AT-DILI and to examine genetic interactions that may lead to isoniazid (INH)-induced hepatotoxicity. We performed a targeted sequencing analysis of 380 pharmacogenes in a discovery cohort of 112 patients (35 AT-DILI patients and 77 controls) receiving AT treatment for active tuberculosis. Pharmacogenome-wide association analysis was also conducted using 1048 population controls (Korea1K). NAT2 and ATP7B genotypes were analyzed in a replication cohort of 165 patients (37 AT-DILI patients and 128 controls) to validate the effects of both risk genotypes. NAT2 ultraslow acetylators (UAs) were found to have a greater risk of AT-DILI than other genotypes (odds ratio [OR] 5.6 [95% confidence interval; 2.5-13.2], P = 7.2 × 10-6). The presence of ATP7B gene 832R/R homozygosity (rs1061472) was found to co-occur with NAT2 UA in AT-DILI patients (P = 0.017) and to amplify the risk in NAT2 UA (OR 32.5 [4.5-1423], P = 7.5 × 10-6). In vitro experiments using human liver-derived cell lines (HepG2 and SNU387 cells) revealed toxic synergism between INH and Cu, which were strongly augmented in cells with defective NAT2 and ATP7B activity, leading to increased mitochondrial reactive oxygen species generation, mitochondrial dysfunction, DNA damage, and apoptosis. These findings link the co-occurrence of ATP7B and NAT2 genotypes to the risk of INH-induced hepatotoxicity, providing novel mechanistic insight into individual AT-DILI susceptibility. Yoon et al. showed that individuals who carry NAT2 UAs and ATP7B 832R/R genotypes are at increased risk of developing isoniazid hepatotoxicity, primarily due to the increased synergistic toxicity between isoniazid and copper, which exacerbates mitochondrial dysfunction-related apoptosis.

Evaluating the TaqMan Jra-Genotyping Method for Rapidly Predicting the Presence of Anti-Jra Antibodies.

Background: The Jra antigen is a high-prevalence red blood cell (RBC) antigen. Reports on cases of fatal hemolytic disease of the fetus and newborn and acute hemolytic transfusion reactions suggest that antibodies against Jra (anti-Jra) have potential clinical significance. Identifying anti-Jra is challenging owing to a lack of commercially available antisera. We developed an alternative approach to rapidly predict the presence of anti-Jra using the TaqMan single-nucleotide polymorphism (SNP)-genotyping method. Methods: Residual peripheral blood samples from 10 patients suspected of having the anti-Jra were collected. Two samples with confirmed Jr(a-) RBCs and anti-Jra were used to validate the TaqMan genotyping assay by comparing the genotyping results with direct sequencing. The accuracy of the assay in predicting the presence of anti-Jra was verified through crossmatching with in-house Jr(a-) O+ RBCs. Results: The TaqMan-genotyping method was validated with two Jr(a-) RBC- and anti-Jra-confirmed samples that showed concordant Jra genotyping and direct sequencing results. Jra genotyping for the remaining samples and crossmatching the serum samples with in-house Jr(a-) O+ RBCs showed consistent results. Conclusions: We validated a rapid, simple, accurate, and cost-effective method for predicting the presence of anti-Jra using a TaqMan-based SNP-genotyping assay. Implementing this method in routine practice in clinical laboratories will assist in solving difficult problems regarding alloantibodies to high-prevalence RBC antigens and ultimately aid in providing safe and timely transfusions and proper patient care.

Common genes and recurrent causative variants in 957 Asian patients with pediatric epilepsy.

OBJECTIVE: We aimed to identify common genes and recurrent causative variants in a large group of Asian patients with different epilepsy syndromes and subgroups. METHODS: Patients with unexplained pediatric-onset epilepsy were identified from the in-house Severance Neurodevelopmental Disorders and Epilepsy Database. All patients underwent either exome sequencing or multigene panels from January 2017 to December 2019, at Severance Children's Hospital in Korea. Clinical data were extracted from the medical records. RESULTS: Of the 957 patients studied, 947 (99.0%) were Korean and 570 were male (59.6%). The median age at testing was 4.91 years (interquartile range, 1.53-9.39). The overall diagnostic yield was 32.4% (310/957). Clinical exome sequencing yielded a diagnostic rate of 36.9% (134/363), whereas the epilepsy panel yielded a diagnostic rate of 29.9% (170/569). Diagnostic yield differed across epilepsy syndromes. It was high in Dravet syndrome (87.2%, 41/47) and early infantile developmental epileptic encephalopathy (60.7%, 17/28), but low in West syndrome (21.8%, 34/156) and myoclonic-atonic epilepsy (4.8%, 1/21). The most frequently implicated genes were SCN1A (n = 49), STXBP1 (n = 15), SCN2A (n = 14), KCNQ2 (n = 13), CDKL5 (n = 11), CHD2 (n = 9), SLC2A1 (n = 9), PCDH19 (n = 8), MECP2 (n = 6), SCN8A (n = 6), and PRRT2 (n = 5). The recurrent genetic abnormalities included 15q11.2 deletion/duplication (n = 9), Xq28 duplication (n = 5), PRRT2 deletion (n = 4), MECP2 duplication (n = 3), SCN1A, c.2556+3A>T (n = 3), and 2q24.3 deletion (n = 3). SIGNIFICANCE: Here we present the results of a large-scale study conducted in East Asia, where we identified several common genes and recurrent variants that varied depending on specific epilepsy syndromes. The overall genetic landscape of the Asian population aligns with findings from other populations of varying ethnicities.

Investigation of blood group genotype prevalence in Korean population using large genomic databases.

Blood group antigens, which are prominently expressed in red blood cells, are important in transfusion medicine. The advent of high-throughput genome sequencing technology has facilitated the prediction of blood group antigen phenotypes based on genomic data. In this study, we analyzed data from a large Korean population to provide an updated prevalence of blood group antigen phenotypes, including rare ones. A robust dataset comprising 72,291 single nucleotide polymorphism arrays, 5318 whole-exome sequences, and 4793 whole-genome sequences was extracted from the Korean Genome and Epidemiology Study, Genome Aggregation Database, and Korean Variant Archive and then analyzed. The phenotype prevalence of clinically significant blood group antigens, including MNSs, RHCE, Kidd, Duffy, and Diego, was predicted through genotype analysis and corroborated the existing literature. We identified individuals with rare phenotypes, including 369 (0.51%) with Fy(a-b+), 188 (0.26%) with Di(a+b-), and 16 (0.02%) with Jr(a-). Furthermore, we calculated the frequencies of individuals with extremely rare phenotypes, such as p (0.000004%), Kell-null (0.000310%), and Jk(a-b-) (0.000438%), based on allele frequency predictions. These findings offer valuable insights into the distribution of blood group antigens in the Korean population and have significant implications for enhancing the safety and efficiency of blood transfusion.

Corrigendum: Genetic diagnosis of inborn errors of immunity using clinical exome sequencing.

[This corrects the article DOI: 10.3389/fimmu.2023.1178582.].

Genetic diagnosis of inborn errors of immunity using clinical exome sequencing.

Inborn errors of immunity (IEI) include a variety of heterogeneous genetic disorders in which defects in the immune system lead to an increased susceptibility to infections and other complications. Accurate, prompt diagnosis of IEI is crucial for treatment plan and prognostication. In this study, clinical utility of clinical exome sequencing (CES) for diagnosis of IEI was evaluated. For 37 Korean patients with suspected symptoms, signs, or laboratory abnormalities associated with IEI, CES that covers 4,894 genes including genes related to IEI was performed. Their clinical diagnosis, clinical characteristics, family history of infection, and laboratory results, as well as detected variants, were reviewed. With CES, genetic diagnosis of IEI was made in 15 out of 37 patients (40.5%). Seventeen pathogenic variants were detected from IEI-related genes, BTK, UNC13D, STAT3, IL2RG, IL10RA, NRAS, SH2D1A, GATA2, TET2, PRF1, and UBA1, of which four variants were previously unreported. Among them, somatic causative variants were identified from GATA2, TET2, and UBA1. In addition, we identified two patients incidentally diagnosed IEI by CES, which was performed to diagnose other diseases of patients with unrecognized IEI. Taken together, these results demonstrate the utility of CES for the diagnosis of IEI, which contributes to accurate diagnosis and proper treatments.

Genotypes and phenotypes of DNM1 encephalopathy.

BACKGROUND: Variants in the dynamin-1 (DNM1) gene typically cause synaptopathy, leading to developmental and epileptic encephalopathy (DEE). We aimed to determine the genotypic and phenotypic spectrum of DNM1 encephalopathy beyond DEE. METHODS: Electroclinical phenotyping and genotyping of patients with a DNM1 variant were conducted for patients undergoing next-generation sequencing at our centre, followed by a systematic review. RESULTS: Six patients with heterozygous DNM1 variants were identified in our cohort. Three had a typical DEE phenotype characterised by epileptic spasms, tonic seizures and severe-to-profound intellectual disability with pathogenic variants located in the GTPase or middle domain. The other three patients had atypical phenotypes of milder cognitive impairment and focal epilepsy. Genotypically, two patients with atypical phenotypes had variants located in the GTPase domain, while the third patient had a novel variant (p.M648R) in the linker region between pleckstrin homology and GTPase effector domains. The third patient with an atypical phenotype showed normal development until he developed febrile status epilepticus. Our systematic review on 55 reported cases revealed that those with GTPase or middle domain variants had more severe intellectual disability (p<0.001) and lower functional levels of ambulation (p=0.001) or speech and language (p<0.001) than the rest. CONCLUSION: DNM1-related phenotypes encompass a wide spectrum of epilepsy and neurodevelopmental disorders, with specific variants underlying different phenotypes.

In vitro erythrocyte production using human-induced pluripotent stem cells: determining the best hematopoietic stem cell sources.

BACKGROUND: Blood transfusion is an essential part of medicine. However, many countries have been facing a national blood crisis. To address this ongoing blood shortage issue, there have been efforts to generate red blood cells (RBCs) in vitro, especially from human-induced pluripotent stem cells (hiPSCs). However, the best source of hiPSCs for this purpose is yet to be determined. METHODS: In this study, hiPSCs were established from three different hematopoietic stem cell sources-peripheral blood (PB), cord blood (CB) and bone marrow (BM) aspirates (n = 3 for each source)-using episomal reprogramming vectors and differentiated into functional RBCs. Various time-course studies including immunofluorescence assay, quantitative real-time PCR, flow cytometry, karyotyping, morphological analysis, oxygen binding capacity analysis, and RNA sequencing were performed to examine and compare the characteristics of hiPSCs and hiPSC-differentiated erythroid cells. RESULTS: hiPSC lines were established from each of the three sources and were found to be pluripotent and have comparable characteristics. All hiPSCs differentiated into erythroid cells, but there were discrepancies in differentiation and maturation efficiencies: CB-derived hiPSCs matured into erythroid cells the fastest while PB-derived hiPSCs required a longer time for maturation but showed the highest degree of reproducibility. BM-derived hiPSCs gave rise to diverse types of cells and exhibited poor differentiation efficiency. Nonetheless, erythroid cells differentiated from all hiPSC lines mainly expressed fetal and/or embryonic hemoglobin, indicating that primitive erythropoiesis occurred. Their oxygen equilibrium curves were all left-shifted. CONCLUSIONS: Collectively, both PB- and CB-derived hiPSCs were favorably reliable sources for the clinical production of RBCs in vitro, despite several challenges that need to be overcome. However, owing to the limited availability and the large amount of CB required to produce hiPSCs, and the results of this study, the advantages of using PB-derived hiPSCs for RBC production in vitro may outweigh those of using CB-derived hiPSCs. We believe that our findings will facilitate the selection of optimal hiPSC lines for RBC production in vitro in the near future.

Predictive indicators for determining red blood cell transfusion strategies in the emergency department.

BACKGROUND AND IMPORTANCE: Appropriate decision-making is critical for transfusions to prevent unnecessary adverse outcomes; however, transfusion in the emergency department (ED) can only be decided based on sparse evidence in a limited time window. OBJECTIVES: This study aimed to identify factors associated with appropriate red blood cell (RBC) transfusion in the ED by analyzing retrospective data of patients who received transfusions at a single center. OUTCOME MEASURES AND ANALYSIS: This study analyzed associations between transfusion appropriateness and sex, age, initial vital signs, an ED triage score [the Korean Triage and Acuity Scale (KTAS)], the length of stay, and the hemoglobin (Hb) concentration. MAIN RESULTS: Of 10 490 transfusions, 10 109 were deemed appropriate, and 381 were considered inappropriate. A younger age ( P  < 0.001) and a KTAS level of 3-5 ( P  = 0.028) were associated with inappropriate transfusions, after adjusting for O 2 saturation and the Hb level. CONCLUSIONS: In this single-center retrospective study, younger age and higher ED triage scores were associated with the appropriateness of RBC transfusions.

Detecting Low-Variant Allele Frequency Mosaic Pathogenic Variants of NF1, TSC2, and AKT3 Genes from Blood in Patients with Neurodevelopmental Disorders.

Growing evidence indicates that early and late postzygotic mosaicism can cause neurodevelopmental disorders (NDDs), but detection of low variant allele frequency (VAF) mosaic variants from blood remains a challenge. Data of 2162 patients with NDDs who underwent conventional genetic tests were reviewed and a deep sequencing was performed using a specifically designed mosaic next-generation sequencing (NGS) panel in the patients with negative genetic test results. Forty-four patents with neurocutaneous syndrome, malformation of cortical development, or nonlesional epileptic encephalopathies were included. In total, mosaic variants were detected from blood in 1.2% (25/2162) of the patients. Using conventional NGS panels, 22 mosaic variants (VAF, 8.8% to 29.8%) were identified in 18 different genes. Using a specifically designed mosaicism NGS panel, three mosaic variants of the NF1, TSC2, and AKT3 genes were identified (VAF, 2.0% to 11.2%). Mosaic variants were found frequently in the patients who had neurocutaneous syndrome (2/7, 28.6%), whereas only one or no mosaic variant was detected for patients who had malformations of cortical development (1/20, 5%) or nonlesional epileptic encephalopathies (0%, 0/17). In summary, mosaic variants that contribute to the spectrum of NDDs can be detected from blood via conventional NGS and specifically designed mosaicism NGS panels, and detection of mosaic variants using blood will increase diagnostic yield.

Integrative analysis of multiple genomic data from intrahepatic cholangiocarcinoma organoids enables tumor subtyping.

As genomic analysis technology has advanced, it has become possible to sub-classify intrahepatic cholangiocarcinoma (ICC) at the histological or molecular level. Here, we verify the recently suggested two subgroups of ICC in the organoids model, compare the characteristics between types. ICC patients are subclassified into small-duct (SD) and large-duct (LD) subtype according to histological characteristics. ICC organoids are established, and unsupervised principal component analysis clustering separates each type of ICC. Differential gene expression reveals enrichment on KRAS, TGFß and ERBB2 signaling pathways in LD-type compared with SD-type (P < 0.05). Gene set enrichment analysis demonstrates that the cholangiocarcinoma class 2 signature, defined by Andersen et al., is enriched in the LD-type (enrichment Score = 2.19, P < 0.001). A protein-protein interaction network analysis identifies ZNF217 as a significant hub protein (odds ratio = 4.96, P = 0.0105). We perform prospective modeling of histological subtype using patient-derived organoids. Moreover, gene expression profiling of ICC organoids enables identification of type-specific targetable pathways.

Incidence and characteristics of hypotensive transfusion reaction: 10-year experience in a single center.

BACKGROUND: Hypotensive transfusion reaction (HyTR) is rare. It is characterized by a rapid onset of hypotension during transfusion, which usually resolves quickly upon cessation of transfusion. Information on the incidence and clinical characteristics of HyTR has been reported in only a few studies. STUDY DESIGN AND METHODS: We retrospectively reviewed HyTR cases from 10-year hemovigilance data in a tertiary care hospital in Seoul, Korea. RESULTS: We identified 37 HyTRs in 35 patients, and the overall incidence of HyTR was 0.50 per 10,000 transfused units. Among the blood components, the incidence of HyTR was highest in filtered random donor platelets (0.75 per 10,000 units). About half of the HyTRs occurred within 15 min after the start of transfusion (19/37). Blood pressure returned to the normal range within an hour in 73.0% of the cases (27/37). All HyTR cases recovered without severe complications. Known risk factors for HyTR were not prominent in our cohort of patients, with no patients taking angiotensin-converting enzyme inhibitors and only five patients transfused with bedside filtered platelets. DISCUSSION: HyTR can occur in patients with various conditions and types of blood components. Understanding the clinical characteristics of HyTR facilitates proper management, leading to improved transfusion safety.

Analysis of trio test in neurodevelopmental disorders.

Background: Trio test has been widely used for diagnosis of various hereditary disorders. We aimed to investigate the contribution of trio test in genetically diagnosing neurodevelopmental disorders (NDD). Methods: We retrospectively reviewed 2,059 NDD cases with genetic test results. The trio test was conducted in 563 cases. Clinical usefulness, optimal timing, and methods for the trio test were reviewed. Results: Pathogenic or likely pathogenic variants were detected in 112 of 563 (19.9%) patients who underwent the trio test. With trio test results, the overall diagnostic yield increased by 5.4% (112/2,059). Of 165 de novo variants detected, 149 were pathogenic and we detected 85 novel pathogenic variants. Pathogenic, de novo variants were frequently detected in CDKL5, ATP1A3, and STXBP1. Conclusion: The trio test is an efficient method for genetically diagnosing NDD. We identified specific situations where a certain trio test is more appropriate, thereby providing a guide for clinicians when confronted with variants of unknown significance of specific genes.

Cancer-initiating cells in human pancreatic cancer organoids are maintained by interactions with endothelial cells.

Pancreatic ductal adenocarcinoma (PDAC) shows poor prognosis and high malignancy due to the presence of cancer-initiating cells (CICs) and characteristics of the tumor microenvironment (TME). Organoids are useful for studying PDAC, and establishing organoids is dependent on stem cell growth factors, including Wnt signaling. Herein, using a conventional organoid culture system, we demonstrated that CD44(+)CD24(+) and CD44(+)CD24(+)EpCAM(+) CICs were enriched >65% in a PDAC patient-derived organoid. CICs expressing CD44 formed lumen structures by gathering into circles. Additionally, organoid-derived CD44(-) cancer cells were capable of organoid re-formation and could be re-programed as CD44-expressing CICs in the organoid culture system. To mimic a TME absent artificial stem cell growth factors, a PDAC organoid with vascular niche was established. CICs in the PDAC tumor organoid were maintained by paracrine effects and direct interactions with endothelial cells. Interestingly, CD44(+) cells in PDAC tumor tissue were detected primarily in the vascular niche. Inhibiting both Wnt and Notch signaling in endothelial cells suppressed organoid formation and the maintenance of CD24(+)CD44(+) CICs. Collectively, our results suggest that PDAC patient-derived organoids maintain CICs by interacting with endothelial cells via Wnt and Notch pathways.

In silico evaluation of the acute occlusion effect of coronary artery on cardiac electrophysiology and the body surface potential map.

Body surface potential map, an electric potential distribution on the body torso surface, enables us to infer the electrical activities of the heart. Therefore, observing electric potential projected to the torso surface can be highly useful for diagnosing heart diseases such as coronary occlusion. The BSPM for the heart of a patient show a higher level of sensitivity than 12-lead ECG. Relevant research has been mostly based on clinical statistics obtained from patients, and, therefore, a simulation for a variety of pathological phenomena of the heart is required. In this study, by using computer simulation, a body surface potential map was implemented according to various occlusion locations (distal, mid, proximal occlusion) in the left anterior descending coronary artery. Electrophysiological characteristics of the body surface during the ST segment period were observed and analyzed based on an ST isointegral map. We developed an integrated system that takes into account the cellular to organ levels, and performed simulation regarding the electrophysiological phenomena of the heart that occur during the first 5 minutes (stage 1) and 10 minutes (stage 2) after commencement of coronary occlusion. Subsequently, we calculated the bipolar angle and amplitude of the ST isointegral map, and observed the correlation between the relevant characteristics and the location of coronary occlusion. In the result, in the ventricle model during the stage 1, a wider area of ischemia led to counterclockwise rotation of the bipolar angle; and, during the stage 2, the amplitude increased when the ischemia area exceeded a certain size.

A High Alanine Aminotransferase/Aspartate Aminotransferase Ratio Determines Insulin Resistance and Metabolically Healthy/Unhealthy Obesity in a General Adult Population in Korea: The Korean National Health and Nutritional Examination Survey 2007-2010.

AIMS: Early identification of individuals with insulin resistance (IR) and metabolically unhealthy state can help prevent various diseases and improve quality of life. In this study, we investigated a possible marker of IR and metabolic health status, alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratio, and aimed to confirm its feasibility in a large population study. METHODS: A total of 16,371 adults from Korean National Health and Examination Survey were studied. Participants were divided into four groups according to their ALT/AST ratio quartiles. The homeostatic model assessment of insulin resistance level and proportion of people with IR, impaired fasting glucose, and undiagnosed type 2 diabetes were compared for each group. Receiver-operating characteristics (ROC) curve was also used to assess the usefulness of ALT/AST ratio to identify individuals with IR and metabolically unhealthy. RESULTS: In the groups with higher ALT/AST ratio, HOMA-IR level, proportion of IR, and proportion of individuals with IFG or type 2 diabetes mellitus was higher than that in those with low ALT/AST ratio. When analyzed with other factors related to IR, the data showed that the ALT/AST ratio was an independent predictor of IR (odds ratio 1.363, 95% confidential interval 1.323-1.405, p<0.001). When ROC curve analysis was done, area under curve (AUC) for identifying individuals with IR was 0.634. In addition, metabolically unhealthy individuals showed significantly higher ALT/AST ratio than metabolically healthy individuals (0.9780 vs 0.8511, p<0.001). CONCLUSIONS: ALT/AST ratio was well-correlated with IR, IR-related conditions, and metabolic health status. This easily accessible method to estimate IR may facilitate the early screening of IR, which can result in prevention of IR-related morbid conditions.