Immune-checkpoint proteins, cytokines, and microbiome impact on patients with cervical insufficiency and preterm birth

BackgroundMicroenvironmental factors, including microbe-induced inflammation and immune-checkpoint proteins that modulate immune cells have been associated with both cervical insufficiency and preterm delivery. These factors are incompletely understood. This study aimed to explore and compare interactions among microbiome and inflammatory factors, such as cytokines and immune-checkpoint proteins, in patients with cervical insufficiency and preterm birth. In particular, factors related to predicting preterm birth were identified and the performance of the combination of these factors was evaluated.MethodsA total of 220 swab samples from 110 pregnant women, prospectively recruited at the High-Risk Maternal Neonatal Intensive Care Center, were collected between February 2020 and March 2021. This study included 63 patients with cervical insufficiency receiving cerclage and 47 control participants. Endo- and exocervical swabs and fluids were collected simultaneously. Shotgun metagenomic sequencing for the microbiome and the measurement of 34 immune-checkpoint proteins and inflammatory cytokines were performed.ResultsFirst, we demonstrated that immune-checkpoint proteins, the key immune-regulatory molecules, could be measured in endocervical and exocervical samples. Secondly, we identified significantly different microenvironments in cervical insufficiency and preterm birth, with precise cervical locations, to provide information about practically useful cervical locations in clinical settings. Finally, the presence of Moraxella osloensis (odds ratio = 14.785; P = 0.037) and chemokine CC motif ligand 2 levels higher than 73 pg/mL (odds ratio = 40.049; P = 0.005) in endocervical samples were associated with preterm birth. Combining M. osloensis and chemokine CC motif ligand 2 yielded excellent performance for predicting preterm birth (area under the receiver operating characteristic curve = 0.846, 95% confidence interval = 0.733-0.925).ConclusionMultiple relationships between microbiomes, immune-checkpoint proteins, and inflammatory cytokines in the cervical microenvironment were identified. We focus on these factors to aid in the comprehensive understanding and therapeutic modulation of local microbial and immunologic compositions for the management of cervical insufficiency and preterm birth

A Trp33Arg Mutation at Exon 1 of the MYH9 Gene in a Korean Patient with May-Hegglin Anomaly

In this report, we describe a Korean patient with May-Hegglin anomaly from a mutation of the MYH9 gene. The proband was a 21-year-old man with thrombocytopenia. He did not have a bleeding tendency. His neutrophil count was normal at 7490/mm3; however, the neutrophils contained abnormal basophilic inclusions in their cytoplasm. The platelet count was decreased at 15000/mm3 with giant platelets. Coagulation test results were not remarkable. Direct sequencing of MYH9 revealed that he was heterozygous for a mutation in exon 1, which was a 97T>A substitution mutation affecting codon 33, substituting tryptophan with arginine (Trp33Arg). Family study showed that both of his parents had normal phenotype and genotypes, indicating a de novo occurrence of the mutation in the proband

Permissive Hypotension in Extremely Low Birth Weight Infants (≤1000 gm)

∙ The authors have no financial conflicts of interest. © Copyright: Yonsei University College of Medicine 2012 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Licens

Currently Applied Molecular Assays for Identifying ESR1 Mutations in Patients with Advanced Breast Cancer

Approximately 70% of breast cancers, the leading cause of cancer-related mortality worldwide, are positive for the estrogen receptor (ER). Treatment of patients with luminal subtypes is mainly based on endocrine therapy. However, ER positivity is reduced and ESR1 mutations play an important role in resistance to endocrine therapy, leading to advanced breast cancer. Various methodologies for the detection of ESR1 mutations have been developed, and the most commonly used method is next-generation sequencing (NGS)-based assays (50.0%) followed by droplet digital PCR (ddPCR) (45.5%). Regarding the sample type, tissue (50.0%) was more frequently used than plasma (27.3%). However, plasma (46.2%) became the most used method in 2016–2019, in contrast to 2012–2015 (22.2%). In 2016–2019, ddPCR (61.5%), rather than NGS (30.8%), became a more popular method than it was in 2012–2015. The easy accessibility, non-invasiveness, and demonstrated usefulness with high sensitivity of ddPCR using plasma have changed the trends. When using these assays, there should be a comprehensive understanding of the principles, advantages, vulnerability, and precautions for interpretation. In the future, advanced NGS platforms and modified ddPCR will benefit patients by facilitating treatment decisions efficiently based on information regarding ESR1 mutations

Currently Used Laboratory Methodologies for Assays Detecting PD-1, PD-L1, PD-L2 and Soluble PD-L1 in Patients with Metastatic Breast Cancer

Approximately 20% of breast cancer (BC) patients suffer from distant metastasis. The incidence and prevalence rates of metastatic BC have increased annually. Immune checkpoint inhibitors are an emerging area of treatment, especially for metastatic patients with poor outcomes. Several antibody drugs have been developed and approved for companion testing of the programmed death protine-1 (PD-1) axis. We reviewed currently used laboratory methodologies for assays determining PD-1 axis to provide a comprehensive understanding of principles, advantages, and drawbacks involved in their implementation. The most commonly used method is immunohistochemistry (92.9%) for PD-L1 expression using tissue samples (96.4%). The commonly used anti-PD-L1 antibody clone were commercially available 22C3 (30.8%), SP142 (19.2%), SP263 (15.4%), and E1L3N (11.5%). Enzyme-linked immunosorbent assay and electrochemiluminescent immunoassay that target soluble PD-ligand (L)1 were developed and popularized in 2019–2021, in contrast to 2016–2018. Easy accessibility and non-invasiveness due to the use of blood samples, quantitative outputs, and relatively rapid turnaround times make them more preferable. Regarding scoring methods, a combination of tumor and immune cells (45.5% in 2016–2018 to 57.1% in 2019–2021) rather than each cell alone became more popular. Information about antibody clones, platforms, scoring methods, and related companion drugs is recommended for reporting PD-L1 expression

Evaluation of an automated connective tissue disease screening assay in Korean patients with systemic rheumatic diseases

<div><p>This study aimed to evaluate the diagnostic utilities of the automated connective tissues disease screening assay, CTD screen, in patients with systemic rheumatic diseases. A total of 1093 serum samples were assayed using CTD screen and indirect immunofluorescent (IIF) methods. Among them, 162 were diagnosed with systemic rheumatic disease, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and mixed connective tissue disease (MCT). The remaining 931 with non-systemic rheumatic disease were assigned to the control group. The median ratios of CTD screen tests were significantly higher in the systemic rheumatic disease group than in the control group. The positive likelihood ratios of the CTD screen were higher than those of IIF in patients with total rheumatic diseases (4.1 vs. 1.6), including SLE (24.3 vs. 10.7). The areas under the receiver operating characteristic curves (ROC-AUCs) of the CTD screen for discriminating total rheumatic diseases, RA, SLE, and MCT from controls were 0.68, 0.56, 0.92 and 0.80, respectively. The ROC-AUCs of the combinations with IIF were significantly higher in patients with total rheumatic diseases (0.72) and MCT (0.85) than in those of the CTD screen alone. Multivariate analysis indicated that both the CTD screen and IIF were independent variables for predicting systemic rheumatic disease. CTD screen alone and in combination with IIF were a valuable diagnostic tool for predicting systemic rheumatic diseases, particularly for SLE.</p></div

Prevalence and Clinical Impact of Coinfection in Patients with Coronavirus Disease 2019 in Korea

Coinfection rates with other pathogens in coronavirus disease 2019 (COVID-19) varied during the pandemic. We assessed the latest prevalence of coinfection with viruses, bacteria, and fungi in COVID-19 patients for more than one year and its impact on mortality. A total of 436 samples were collected between August 2020 and October 2021. Multiplex real-time PCR, culture, and antimicrobial susceptibility testing were performed to detect pathogens. The coinfection rate of respiratory viruses in COVID-19 patients was 1.4%. Meanwhile, the rates of bacteria and fungi were 52.6% and 10.5% in hospitalized COVID-19 patients, respectively. Respiratory syncytial virus, rhinovirus, Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans were the most commonly detected pathogens. Ninety percent of isolated A. baumannii was non-susceptible to carbapenem. Based on a multivariate analysis, coinfection (odds ratio [OR] = 6.095), older age (OR = 1.089), and elevated lactate dehydrogenase (OR = 1.006) were risk factors for mortality as a critical outcome. In particular, coinfection with bacteria (OR = 11.250), resistant pathogens (OR = 11.667), and infection with multiple pathogens (OR = 10.667) were significantly related to death. Screening and monitoring of coinfection in COVID-19 patients, especially for hospitalized patients during the pandemic, are beneficial for better management and survival

Multivariate analysis^a of the outcomes of systematic rheumatic disease.

<p>Multivariate analysis<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0173597#t004fn002" target="_blank">^a</a> of the outcomes of systematic rheumatic disease.</p