How single-cell techniques help us look into lung cancer heterogeneity and immunotherapy.

Lung cancer patients tend to have strong intratumoral and intertumoral heterogeneity and complex tumor microenvironment, which are major contributors to the efficacy of and drug resistance to immunotherapy. From a new perspective, single-cell techniques offer an innovative way to look at the intricate cellular interactions between tumors and the immune system and help us gain insights into lung cancer and its response to immunotherapy. This article reviews the application of single-cell techniques in lung cancer, with focuses directed on the heterogeneity of lung cancer and the efficacy of immunotherapy. This review provides both theoretical and experimental information for the future development of immunotherapy and personalized treatment for the management of lung cancer.

Vaginal microecological imbalance and expression of serum inflammatory factors in pregnant women with group B streptococcus infection and pregnancy outcome.

The objective of this study was to explore the correlation between vaginal microecological imbalance and the expression of related inflammatory factors in pregnant women with group B streptococcus (GBS) infection and pregnancy outcomes. For this purpose, 100 GBS-positive pregnant women were recruited as the experimental group, and 100 GBS-negative pregnant women were recruited as the controls. The balance of vaginal microecology of pregnant women in different groups was compared. Results showed that the probability of vaginal microecological imbalance in the experimental group was much higher than against the controls. Fasting venous blood was drawn from the pregnant women in two groups. After centrifugation, the expression levels of interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and interleukin-1ß (IL-1ß) in serum were detected. It was found that the expression levels of IL-6, IL-1ß, and TNF-α in the experimental group were higher than against the controls. After delivery, it suggested that the incidence of premature delivery, neonatal infection, premature rupture of membranes, and other adverse childbirth in the experimental group was much higher in contrast to the controls, up to 87%. In conclusion, GBS infection can increase the incidence of vaginal microecological imbalance and the expression of serum inflammatory factors in pregnant women, and it can greatly raise the incidence of adverse pregnancy outcomes.

Diagnostic performance of microRNA-29a in active pulmonary tuberculosis: a systematic review and meta-analysis

Abstract Background: In recent years, more and more studies have shown that microRNA-29a (miRNA-29a) can be used as a potential biomarker for active tuberculosis, but the results of these studies are not consistent. Objective: To comprehensively evaluate the value of miRNA-29a in the diagnosis of active tuberculosis by meta-analysis. Methods: The databases of CNKI, WanFang, PubMed, The Cochrane Library, Web of Science and EMBASE were searched for relevant studies. Studies were screened strictly according to inclusion and exclusion criteria. QUA-DAS-2 scale was used to evaluate the quality of the included studies. Data were extracted and analyzed by Meta-DiSc 1.4 and Stata 16.0 software. Results: 13 articles were included, including a total of 1598 subjects, including 872 active tuberculosis patients and 726 controls. The combined sensitivity and specificity of miRNA-29a in the diagnosis of active tuberculosis were 78 % and 76 %, respectively, and the area under the overall summary receiver operating characteristic curve was 0.8564. Conclusion: miRNA-29a can be used as a biomarker for the diagnosis of active tuberculosis.

Machine learning for identifying benign and malignant of thyroid tumors: A retrospective study of 2,423 patients.

Thyroid tumors, one of the common tumors in the endocrine system, while the discrimination between benign and malignant thyroid tumors remains insufficient. The aim of this study is to construct a diagnostic model of benign and malignant thyroid tumors, in order to provide an emerging auxiliary diagnostic method for patients with thyroid tumors. The patients were selected from the Chongqing General Hospital (Chongqing, China) from July 2020 to September 2021. And peripheral blood, BRAFV600E gene, and demographic indicators were selected, including sex, age, BRAFV600E gene, lymphocyte count (Lymph#), neutrophil count (Neu#), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), red blood cell distribution width (RDW), platelets count (PLT), red blood cell distribution width-coefficient of variation (RDW-CV), alkaline phosphatase (ALP), and parathyroid hormone (PTH). First, feature selection was executed by univariate analysis combined with least absolute shrinkage and selection operator (LASSO) analysis. Afterward, we used machine learning algorithms to establish three types of models. The first model contains all predictors, the second model contains indicators after feature selection, and the third model contains patient peripheral blood indicators. The four machine learning algorithms include extreme gradient boosting (XGBoost), random forest (RF), light gradient boosting machine (LightGBM), and adaptive boosting (AdaBoost) which were used to build predictive models. A grid search algorithm was used to find the optimal parameters of the machine learning algorithms. A series of indicators, such as the area under the curve (AUC), were intended to determine the model performance. A total of 2,042 patients met the criteria and were enrolled in this study, and 12 variables were included. Sex, age, Lymph#, PLR, RDW, and BRAFV600E were identified as statistically significant indicators by univariate and LASSO analysis. Among the model we constructed, RF, XGBoost, LightGBM and AdaBoost with the AUC of 0.874 (95% CI, 0.841-0.906), 0.868 (95% CI, 0.834-0.901), 0.861 (95% CI, 0.826-0.895), and 0.837 (95% CI, 0.802-0.873) in the first model. With the AUC of 0.853 (95% CI, 0.818-0.888), 0.853 (95% CI, 0.818-0.889), 0.837 (95% CI, 0.800-0.873), and 0.832 (95% CI, 0.797-0.867) in the second model. With the AUC of 0.698 (95% CI, 0.651-0.745), 0.688 (95% CI, 0.639-0.736), 0.693 (95% CI, 0.645-0.741), and 0.666 (95% CI, 0.618-0.714) in the third model. Compared with the existing models, our study proposes a model incorporating novel biomarkers which could be a powerful and promising tool for predicting benign and malignant thyroid tumors.

Serum peptidome profiles immune response of COVID-19 Vaccine administration.

Background: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused significant loss of life and property. In response to the serious pandemic, recently developed vaccines against SARS-CoV-2 have been administrated to the public. Nevertheless, the research on human immunization response against COVID-19 vaccines is insufficient. Although much information associated with vaccine efficacy, safety and immunogenicity has been reported by pharmaceutical companies based on laboratory studies and clinical trials, vaccine evaluation needs to be extended further to better understand the effect of COVID-19 vaccines on human beings. Methods: We performed a comparative peptidome analysis on serum samples from 95 participants collected at four time points before and after receiving CoronaVac. The collected serum samples were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to profile the serum peptides, and also subjected to humoral and cellular immune response analyses to obtain typical immunogenicity information. Results: Significant difference in serum peptidome profiles by MALDI-TOF MS was observed after vaccination. By supervised statistical analysis, a total of 13 serum MALDI-TOF MS feature peaks were obtained on day 28 and day 42 of vaccination. The feature peaks were identified as component C1q receptor, CD59 glycoprotein, mannose-binding protein C, platelet basic protein, CD99 antigen, Leucine-rich alpha-2-glycoprotein, integral membrane protein 2B, platelet factor 4 and hemoglobin subunits. Combining with immunogenicity analysis, the study provided evidence for the humoral and cellular immune responses activated by CoronaVac. Furthermore, we found that it is possible to distinguish neutralizing antibody (NAbs)-positive from NAbs-negative individuals after complete vaccination using the serum peptidome profiles by MALDI-TOF MS together with machine learning methods, including random forest (RF), partial least squares-discriminant analysis (PLS-DA), linear support vector machine (SVM) and logistic regression (LR). Conclusions: The study shows the promise of MALDI-TOF MS-based serum peptidome analysis for the assessment of immune responses activated by COVID-19 vaccination, and discovered a panel of serum peptides biomarkers for COVID-19 vaccination and for NAbs generation. The method developed in this study can help not only in the development of new vaccines, but also in the post-marketing evaluation of developed vaccines.

Highly sensitive fluorescence multiplexed miRNAs biosensors for accurate clinically diagnosis lung cancer disease using LNA-modified DNA probe and DSN enzyme.

With the emergence of microRNAs as key biomarkers for disease diagnosis such as lung cancer, various techniques have been settled for their detection. However, these current methods require different amplification steps since numerous challenges for detecting circulating miRNAs are attributable to their intrinsic properties accounting for tiny sizes, high sequence similarity, and low abundance. Duplex specific nuclease (DSN)-based microRNA amplification has recently gained interest in biosensing applications thanks to its catalytic activity based on target recycling. In this context, we designed a highly selective, sensitive, and multiplexed fluorescence-based biosensor combining DSN enzyme and magnetic beads to detect three distinct microRNAs, including microRNA-21, microRNA-210, and microRNA-486-5p. By exploiting the above approach, we were able to detect as low as 98 aM, 120 aM, and 300 aM of mir-21, miR-210, and miR-486-5p, respectively. Furthermore, this recommended strategy displays a high selectivity toward an entirely matched target than the off-target. These results are ascribed to the potent DSN enzyme activity and to the locked nucleic acid (LNA)-modified DNA probe that boosted the hetero-duplex probe/target stability. Lastly, our proposed method was applied to detect microRNAs in the serum samples and displayed a high efficacy to discriminate between healthy controls and lung cancer patients. Furthermore, the analytical accuracy of the proposed strategy was validated with the computed tomography (CT) technique of the chest. Thus based on these findings, this strategy could open new directions for detecting microRNAs associated with several diseases.

Janus wireframe DNA cube-based 3D nanomachine for rapid and stable fluorescence detection of exosomal microRNA.

Exosomal microRNAs (miRNAs) have been demonstrated to be credible biomarkers for the diagnosis and monitoring of tumors. Nevertheless, developing simple, rapid, and stable biosensing strategies that are capable of accurately detecting exosomal miRNAs remains a challenge. Herein, an accelerated and biostable three-dimensional (3D) nanomachine based on Janus wireframe DNA cube was constructed for sensitive fluorescence measurement of exosomal miRNA. The Janus wireframe DNA cube could propel target exosomal miRNA-21 rapid movement on its surface by catalytic hairpin assembly (CHA), releasing a massive fluorescence signal. Benefiting from the Janus wireframe DNA cube, the developed 3D nanomachine exhibited significantly improved reaction rate and enhanced biostability in complex biofluids compared to conventional CHA. As a result, this fluorescence biosensing strategy achieved rapid, stable, and single-step detection of exosomal miRNA-21 with the detection limit down to the picomole level. Therefore, this work offers a brief sensing tool for nucleic acid biomarkers detection, which has great application potential in tumor diagnosis.

Rapid Detection of COVID-19 Using MALDI-TOF-Based Serum Peptidome Profiling.

The outbreak of coronavirus disease 2019 (COVID-19) caused by SARS CoV-2 is ongoing and a serious threat to global public health. It is essential to detect the disease quickly and immediately to isolate the infected individuals. Nevertheless, the current widely used PCR and immunoassay-based methods suffer from false negative results and delays in diagnosis. Herein, a high-throughput serum peptidome profiling method based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is developed for efficient detection of COVID-19. We analyzed the serum samples from 146 COVID-19 patients and 152 control cases (including 73 non-COVID-19 patients with similar clinical symptoms, 33 tuberculosis patients, and 46 healthy individuals). After MS data processing and feature selection, eight machine learning methods were used to build classification models. A logistic regression machine learning model with 25 feature peaks achieved the highest accuracy (99%), with sensitivity of 98% and specificity of 100%, for the detection of COVID-19. This result demonstrated a great potential of the method for screening, routine surveillance, and diagnosis of COVID-19 in large populations, which is an important part of the pandemic control.

Identification of a prognostic signature based on copy number variations (CNVs) and CNV-modulated gene expression in acute myeloid leukemia.

OBJECTIVES: Acute myeloid leukemia (AML) is caused by multiple genetic alterations in hematopoietic progenitors, and molecular genetic analyses have provided useful information for AML diagnosis and prognostication. This study aimed to integratively understand the prognostic value of specific copy number variation (CNV) patterns and CNV-modulated gene expression in AML. METHODS: We conducted integrative CNV profiling and gene expression analysis using data from the Therapeutically Applicable Research To Generate Effective Treatments (TARGET) and The Cancer Genome Atlas (TCGA) AML cohorts. CNV-related genes associated with survival were identified using the TARGET AML cohort and validated using the TCGA AML cohort. Genes whose CNV-modulated expression was associated with survival were also identified using the TARGET AML cohort and validated using the TCGA AML cohort, and patient bone marrow samples were then used to further validate the effects of CNV-modulated gene expression on survival. CNV and mRNA survival analyses were conducted using proportional hazards regression models (Cox regression) and the "survminer" and "survival" packages of the R Project for Statistical Computing. Genes belonging to the Kyoto Encyclopedia of Genes and Genomes (KEGG) cancer panel were extracted from KEGG cancer-related pathways. RESULTS: One hundred two CNV-related genes (located at 7q31-34, 16q24) associated with patient survival were identified using the TARGET cohort and validated with the TCGA AML cohort. Among these 102 validated genes, three miRNA genes (MIR29A, MIR183, and MIR335) were included in the KEGG cancer panel. Five genes (SEMA4D, CBFB, CHAF1B, SAE1, and DNMT1) whose expression was modulated by CNVs and significantly associated with clinical outcomes were identified, and the deletion of SEMA4D and CBFB was found to potentially exert protective effects against AML. The results of these five genes were also validated using patient marrow samples. Additionally, the distribution of CNVs affecting these five CNV-modulated genes was independent of the risk group (favorable-, intermediate-, and adverse-risk groups). CONCLUSIONS: Overall, this study identified 102 CNV-related genes associated with patient survival and identified five genes whose expression was modulated by CNVs and associated with patient survival. Our findings are crucial for the development of new modes of prognosis evaluation and targeted therapy for AML.

Efficacy of Chemiluminescence Immunoassays on VCA-IgA and EBNA1-IgA Antibodies of Epstein-Barr Virus in Diagnosing Nasopharyngeal Carcinoma.

Background: IgA antibodies against Epstein-Barr virus (EBV) capsid antigen (VCA) and nuclear antigen 1 (EBNA1) have been proposed to facilitate the diagnosis and early detection of nasopharyngeal carcinoma (NPC) in high-incidence regions. However, while new methodologies and new platforms for the detection of VCA-IgA and EBNA1-IgA have become available, proper interassay simultaneous comparisons have not been carried out. The study was to compare the performance of the chemiluminescent immunoassays (CLIA) and enzyme-linked immunosorbent assay (ELISA) for VCA-IgA and EBNA1-IgA antibodies, and to evaluate the levels of EBV antibodies in healthy population from different areas of China. Methods: CLIA and ELISA for VCA-IgA and EBNA1-IgA were performed in NPC and healthy populations from high-incidence areas of NPC in South China (N=555), medium-incidence areas of NPC in Central China (N=318) and low-incidence areas of NPC in North China (N=379), and the results were compared and analyzed. Results: (1) The highest sensitivity in total, early and advanced NPC were 91.5% (CLIA for VCA-IgA), 86.4% (CLIA and ELISA-2 for EBNA1-IgA) and 93.6% (CLIA for VCA-IgA). However, the specificity of EBV-IgA measured by CLIA was relatively lower than ELISA. The top three seromarkers with the largest AUC was CLIA for VCA-IgA (AUC: 0.929, 95% CI: 0.905-0.953), ELISA-2 for EBNA1-IgA (AUC: 0.922, 95% CI: 0.896-0.947) and CLIA for EBNA1-IgA (AUC:0.919, 95% CI: 0.893-0.945), respectively. The positive and negative coincidence rates of the two EBNA1-IgA kits were 69.5% and 91.9%, respectively. However, the coincidence rates of VCA-IgA were relatively low. CLIA kits had good repeatability between different laboratories. (2) The positive rates of EBV-IgA antibodies were relatively high in high-incidence areas of NPC (P < 0.017), while there was no significant difference in the antibody positive rates between medium-incidence areas and low-incidence areas of NPC (P > 0.05). Conclusions: The performance of EBV-IgA antibodies measured by CLIA has good repeatability, higher sensitivity and similar specificity. The higher EBV-IgA positive rate in healthy subjects by CLIA raises concern about its suitability for NPC-risk screening and requires further analysis.

Performance verification of anti-SARS-CoV-2-specific antibody detection by using four chemiluminescence immunoassay systems.

OBJECTIVES: The purpose of the current study was to evaluate the analytical performance of seven kits for detecting IgM/IgG antibodies against coronavirus (SARS-CoV-2) by using four chemiluminescence immunoassay systems. METHODS: Fifty patients diagnosed with SARS-CoV-2 infection and 130 controls without coronavirus infection from the General Hospital of Chongqing were enrolled in the current retrospective study. Four chemiluminescence immunoassay systems, including seven IgM/IgG antibody detection kits for SARS-CoV-2 (A_IgM, A_IgG, B_IgM, B_IgG, C_IgM, C_IgG and D_Ab), were employed to detect antibody concentrations. The chi-square test, the receiver operating characteristic (ROC) curve and Youden's index were determined to verify the cut-off value of each detection system. RESULTS: The repeatability verification results of the A, B, C and D systems are all qualified. D_Ab performed best (92% sensitivity and 99.23% specificity), and B_IgM performed worse than the other systems. Except for the A_IgM and C_IgG systems, the optimal diagnostic thresholds and cut-off values of the other kits and their recommendations are inconsistent with each other. B_IgM had the worst AUC, and C_IgG had the best diagnostic accuracy. More importantly, the B_IgG system had the highest false-positive rate for testing patients with AIDS, tumours and pregnancies. The A_IgM system test showed the highest false-positive rates among elderly individuals over 90 years old. COVID-2019 IgM/IgG antibody test systems exhibit performance differences. CONCLUSIONS: The Innodx Biotech Total Antibody serum diagnosis kit is the most reliable detection system for anti-SARS-CoV-2 antibodies, which can be used together with nucleic acid tests as an alternative method for SARS-CoV-2 detecting.

Calcium Sensing Receptor Inhibits Growth of Human Lung Adenocarcinoma Possibly via the GSK3ß/Cyclin D1 Pathway.

The effect of calcium sensing receptor (CaSR) on tumor cell proliferation has been studied in several human cancers, and great discrepancies were found in different tumors. However, the role of CaSR in lung adenocarcinomas (LUADs) is not clear. Therefore, we investigated the function of CaSR on regulating the growth of human LUAD and its possible mechanism. The expression of CaSR protein and its relationship with pathological parameters were examined in paraffin sections from 51 LUAD patients, by immunohistochemistry. The results showed that CasR expression was negatively correlated with the Ki-67 index as well as the grade of malignancy in LUAD. Further, CaSR demonstrated an in vitro inhibitory effect on the proliferation of human LUAD A549 cells by regulating CaSR activity with agonist cinacalcet, antagonist NPS2143, or shRNA-CaSR transfection. Tumor xenograft models also verified the in vivo proliferation-inhibiting role of CaSR by subcutaneous injecting A549 cells into nude mice with or without changes of CaSR activity. Molecularly, Western blotting showed that CaSR positively regulated the activity of glycogen synthase kinase 3ß (GSK3ß), followed by the downregulation of Cyclin D1. We used the dominant negative mutant and the constitutively active mutant plasmid of GSK3ß to alter GSK3ß activity. Our functional experiments showed that the proliferation-inhibition of CaSR was suppressed by the inactivation of GSK3ß and enhanced by the activation of GSK3ß. These results suggested that CaSR played a proliferation-inhibiting role in LUAD, at least partially by regulating the GSK3ß/Cyclin D1 pathway.

A Peptide-Based Magnetic Chemiluminescence Enzyme Immunoassay for Serological Diagnosis of Coronavirus Disease 2019.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel ß-coronavirus, causes severe pneumonia and has spread throughout the globe rapidly. The disease associated with SARS-CoV-2 infection is named coronavirus disease 2019 (COVID-19). To date, real-time reverse-transcription polymerase chain reaction (RT-PCR) is the only test able to confirm this infection. However, the accuracy of RT-PCR depends on several factors; variations in these factors might significantly lower the sensitivity of detection. METHODS: In this study, we developed a peptide-based luminescent immunoassay that detected immunoglobulin (Ig)G and IgM. The assay cutoff value was determined by evaluating the sera from healthy and infected patients for pathogens other than SARS-CoV-2. RESULTS: To evaluate assay performance, we detected IgG and IgM in the sera from confirmed patients. The positive rate of IgG and IgM was 71.4% and 57.2%, respectively. CONCLUSIONS: Therefore, combining our immunoassay with real-time RT-PCR might enhance the diagnostic accuracy of COVID-19.

Procalcitonin as a prognostic marker of patients with acute ischemic stroke.

BACKGROUND: The information on mortality after an acute stroke patient is still limited. OBJECTIVES: The aim of this study was to investigate the prognostic potential of procalcitonin (PCT) serum levels in acute ischemic stroke. METHODS: A total of 748 patients were enrolled in this study. Prognostic potential of PCT was evaluated by Kaplan-Meier analysis and multivariable Cox hazard regression analyses. RESULTS: Procalcitonin levels were found to be significantly higher in acute ischemic stroke patients who died in 30 days than those who survived. Univariate logistic regression analysis showed that PCT was significantly associated with 30-day mortality, and Cox regression analysis revealed that PCT was a strong predictor of 30-day overall mortality. Kaplan-Meier analysis revealed that overall cumulative 30-day mortality was significantly higher in those with PCT levels >1.5 ng/mL when compared to those with PCT levels <1.5 ng/mL. CONCLUSIONS: Procalcitonin is a significant independent prognostic marker of 30-day mortality after the one set of acute ischemic stroke.

A Novel Electrochemiluminescent Immunoassay Based on Target Transformation Assisted with Catalyzed Hairpin Assembly Amplification for the Ultrasensitive Bioassay.

In this work, we constructed a novel electrochemiluminescent (ECL) strategy based on sandwich immunoassay-induced target transformation assisted with catalyzed hairpin assembly (CHA) amplification for ultrasensitive bioassay with cysteine-rich protein 61 (CCN1) as a model. First, the target CCN1 could be equally transformed into the specific oligonucleotide (initiator I) labeled on the detection antibody based on the specific sandwich immunoassay. In addition, the initiator I triggered an efficient nonenzymatic CHA amplification in the presence of ferrocene-labeled hairpin 1 (Fc-H1) and hairpin 2 (H2) to produce massive hybrids (Fc-H1-H2) containing a sticky end labeled with ferrocene. Finally, Fc-H1-H2 could be immobilized on the capture probe single-stranded DNA (ssDNA)-modified electrode through the hybridization between the sticky end of Fc-H1-H2 and ssDNA, and a significantly quenched ECL signal could be obtained due to the efficient quench effect between ferrocene and the ECL indicator, ruthenium(II) tris(4,4'-dicarboxylicacid-2,2'-bipyridyl) [Ru(dcbpy)32+], immobilized on the surface of the electrode, which was related to the concentration of target CCN1. As expected, the proposed ECL biosensor exhibited a relatively low detection limit of 3.9 fg/mL in a linear range from 10 fg/mL to 100 ng/mL. This ECL strategy inspired the clinical examination of the biomarker CCN1, providing potential application in early diagnosis and malignant monitoring of cancer.

Polymorphisms of the CYR61 gene in patients with acute myeloid leukemia in a Han Chinese population.

It was demonstrated in previous studies that cysteine-rich angiogenic inducer 61 (Cyr61) plays vital roles in hematological disorders, and we have already reported that the Cyr61 protein is a tumor promoter in acute myeloid leukemia (AML). Here, we investigated the association between CYR61 gene polymorphisms and susceptibility to AML.We genotyped 2 single-nucleotide polymorphisms (rs2297141 and rs6576776) in the region of the CYR61 gene by improved multiplex ligase detection reaction genotyping assays in a total of 275 samples, including samples from 137 AML patients and 138 healthy controls. Chi-squared tests and logistic regression analysis were performed to compare the different distributions of the genotypes and alleles between patients and healthy controls.The rs2297141 A allele was associated with lower risk of AML compared with the G allele (odds ratio [OR] = 0.704, 95% confidence interval [CI] = 0.503-0.985, P = .04) in both the dominant (OR = 0.447, 95% CI = 0.22-0.909, P = .025, AA vs GG) and recessive inheritance models (OR = 0.419, 95% CI = 0.23-0.763, P = .004, AA vs GA + GG). Although the distribution of the rs6576776 alleles was not different between patients with AML and normal controls, the CC genotype significantly increased the risk of AML in the dominant inheritance model (OR = 6.064, 95% CI = 1.303-28.216, P = .01, CC vs GG) and the recessive inheritance model (OR = 5.937, 95% CI = 1.291-27.306, P = .01, CC vs GC + GG). Additionally, it was shown that the rs2297141 and rs6576776 genotypes were associated with AML-M5 and AML-M2, respectively.Our findings indicated that genetic polymorphisms in the CYR61 gene may be considered potential AML risk factors in the Han Chinese population.

Postoperative Oxygen Therapy in Patients With OSA: A Randomized Controlled Trial.

BACKGROUND: Surgical patients with OSA are at increased risk for perioperative complications. Postoperative supplemental oxygen is commonly used, but it may contribute to respiratory depression in patients with OSA receiving opioids. The objective of the study is to investigate the effect of postoperative supplemental oxygen on arterial oxygen saturation (Sao2), sleep respiratory events, and CO2 level in patients with untreated OSA. METHODS: Consented patients with an apnea hypopnea index (AHI) > 5 events per hour on a preoperative polysomnography were randomized (1:1) to oxygen (O2 group) or no oxygen (control group). The O2 group received oxygen at 3 L/min via nasal prongs for three postoperative nights. The primary outcomes were polysomnographic parameters measuring Sao2, sleep respiratory events, and Pco2 measured by transcutaneous CO2 monitor (PtcCO2) on nights 1 through 3. The intention-to-treat and per protocol analysis were completed. RESULTS: There were 123 patients randomized (O2 group: n = 62; control group: n = 61). On night 3, the O2 vs control group had a higher average Sao2 (95.2% ± 3% vs 91.4% ± 4%, respectively; P < .001) and lower oxygen desaturation index (median, 2.3; 25th-75th percentile, 0.2-13.8 vs median, 18.5; 25th-75th percentile, 8.2-45.9 events per hour, respectively; P < .0001). The O2 group had a decreased AHI (median, 8.0; 25th-75th percentile, 2.1-19.9 vs median, 15.6; 25th-75th percentile, 9.5-45.8, respectively; P = .016), hypopnea index (P < .001), and central apnea index (P = .026) and a shortened longest apnea hypopnea duration (P = .002). Although time percentage with PtcCO2 ≥ 55 mm Hg ≥ 10% on postoperative night 1, 2, or 3 was found in 11.4% patients, there was no difference in PtcCO2 between the groups. CONCLUSIONS: Postoperative supplemental oxygen was found to improve oxygenation and decrease the AHI without increasing the duration of apnea-hypopnea event or PtcCO2 level. A small number of patients had significant CO2 retention while receiving supplemental oxygen. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01552304; URL: www.clinicaltrials.gov.

STOP-Bang Questionnaire: A Practical Approach to Screen for Obstructive Sleep Apnea.

There exists a high prevalence of OSA in the general population, a great proportion of which remains undiagnosed. The snoring, tiredness, observed apnea, high BP, BMI, age, neck circumference, and male gender (STOP-Bang) questionnaire was specifically developed to meet the need for a reliable, concise, and easy-to-use screening tool. It consists of eight dichotomous (yes/no) items related to the clinical features of sleep apnea. The total score ranges from 0 to 8. Patients can be classified for OSA risk based on their respective scores. The sensitivity of STOP-Bang score ≥ 3 to detect moderate to severe OSA (apnea-hypopnea index [AHI] > 15) and severe OSA (AHI > 30) is 93% and 100%, respectively. Corresponding negative predictive values are 90% and 100%. As the STOP-Bang score increases from 0 to 2 up to 7 to 8, the probability of moderate to severe OSA increases from 18% to 60%, and the probability of severe OSA rises from 4% to 38%. Patients with a STOP-Bang score of 0 to 2 can be classified as low risk for moderate to severe OSA whereas those with a score of 5 to 8 can be classified as high risk for moderate to severe OSA. In patients whose STOP-Bang scores are in the midrange (3 or 4), further criteria are required for classification. For example, a STOP-Bang score of ≥ 2 plus a BMI > 35 kg/m(2) would classify that patient as having a high risk for moderate to severe OSA. In this way, patients can be stratified for OSA risk according to their STOP-Bang scores.

Validation of the STOP-Bang Questionnaire as a Screening Tool for Obstructive Sleep Apnea among Different Populations: A Systematic Review and Meta-Analysis.

BACKGROUND: Diagnosing obstructive sleep apnea (OSA) is clinically relevant because untreated OSA has been associated with increased morbidity and mortality. The STOP-Bang questionnaire is a validated screening tool for OSA. We conducted a systematic review and meta-analysis to determine the effectiveness of STOP-Bang for screening patients suspected of having OSA and to predict its accuracy in determining the severity of OSA in the different populations. METHODS: A search of the literature databases was performed. Inclusion criteria were: 1) Studies that used STOP-Bang questionnaire as a screening tool for OSA in adult subjects (>18 years); 2) The accuracy of the STOP-Bang questionnaire was validated by polysomnography--the gold standard for diagnosing OSA; 3) OSA was clearly defined as apnea/hypopnea index (AHI) or respiratory disturbance index (RDI) ≥ 5; 4) Publications in the English language. The quality of the studies were explicitly described and coded according to the Cochrane Methods group on the screening and diagnostic tests. RESULTS: Seventeen studies including 9,206 patients met criteria for the systematic review. In the sleep clinic population, the sensitivity was 90%, 94% and 96% to detect any OSA (AHI ≥ 5), moderate-to-severe OSA (AHI ≥15), and severe OSA (AHI ≥30) respectively. The corresponding NPV was 46%, 75% and 90%. A similar trend was found in the surgical population. In the sleep clinic population, the probability of severe OSA with a STOP-Bang score of 3 was 25%. With a stepwise increase of the STOP-Bang score to 4, 5, 6 and 7/8, the probability rose proportionally to 35%, 45%, 55% and 75%, respectively. In the surgical population, the probability of severe OSA with a STOP-Bang score of 3 was 15%. With a stepwise increase of the STOP-Bang score to 4, 5, 6 and 7/8, the probability increased to 25%, 35%, 45% and 65%, respectively. CONCLUSION: This meta-analysis confirms the high performance of the STOP-Bang questionnaire in the sleep clinic and surgical population for screening of OSA. The higher the STOP-Bang score, the greater is the probability of moderate-to-severe OSA.

Postoperative sleep-disordered breathing in patients without preoperative sleep apnea.

BACKGROUND: Recently published data show that postoperative apnea-hypopnea index (AHI) is significantly increased in some patients without preoperative sleep apnea. These patients may be at risk of developing perioperative adverse events related to sleep-disordered breathing (SDB). The objective of this study was to investigate the incidence and predictors of postoperative moderate-to-severe SDB (AHI > 15 events/h) in patients without sleep apnea preoperatively. METHODS: In a prospective observational fashion, patients were invited to undergo sleep studies with a portable device (Embletta X100) preoperatively at home and postoperatively on the first and third night after surgery in the hospital or at home. The primary outcome was the incidence of postoperative moderate-to-severe SDB (AHI > 15 events/h) in non-sleep apnea patients (preoperative AHI ≤ 5 events/h). Logistic regression was used to evaluate the association of clinical factors and preoperative sleep parameters with the occurrence of postoperative moderate-to-severe SDB. RESULTS: A total of 120 non-sleep apnea patients completed the study, of which 31 (25.8% [95% confidence interval: 18.3%-34.6%]) patients were found to have AHI > 15 events/h on postoperative night 1 and/or postoperative night 3 (postoperative SDB group), and 89 (74%) patients had an AHI ≤ 15 events/h on both postoperative night 1 and 3 (postoperative non-SDB group). The patients in the postoperative SDB group were older (60 ± 13 vs 53 ± 12 years, P = 0.008) with more smokers (32.3% vs 15.7%, P = 0.048) and had a greater increase in the obstructive apnea index (adjusted P = 0.0003), central apnea index (adjusted P = 0.0012), and hypopnea index (adjusted P = 0.0004). Multivariate logistic regression analysis found that age and preoperative respiratory disturbance index (RDI) were significantly associated with the occurrence of postoperative moderate-to-severe SDB, P = 0.018 and P = 0.006, respectively. The sensitivity privilege cutoff of RDI at 4.9 events/h identified 70.2% to 96.4%patients developing postoperative moderate-to-severe SDB. CONCLUSIONS: At least 18.3% of non-sleep apnea patients developed moderate-to-severe SDB after surgery. Age and preoperative RDI were associated with the occurrence of postoperative moderate-to-severe SDB.