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Is bivalirudin an alternative anticoagulant for extracorporeal membrane oxygenation (ECMO) patients? A systematic review and meta-analysis

Thromb Res. 2021 Dec 31;210:53-62. doi: 10.1016/j.thromres.2021.12.024. Online ahead of print.

ABSTRACT

BACKGROUND: Anticoagulation is important for extracorporeal membrane oxygenation (ECMO). Heparin is widely used; however, in some cases, it is not suitable for patients. Bivalirudin has been recently proposed for ECMO patients, and there is no evidence regarding its effectiveness and safety.

OBJECTIVE: We aimed to systematically review the effectiveness and safety of bivalirudin in ECMO patients.

STUDY DESIGN AND METHODS: PubMed, Web of Science, Cochrane Library, and EMBASE were searched to find relevant research on the use of bivalirudin versus heparin for anticoagulation in ECMO patients. Outcomes included in-hospital mortality, ECMO duration, major bleeding events, thrombosis events and circuit intervention events. Types of studies included randomized control trials (RCTs), cohort studies, and case-control studies. Case reports, studies lacking comparison with heparin, and where patients transitioned between heparin and bivalirudin, were excluded. Publication bias was evaluated when the number of included studies was more than ten. Sensitivity analysis was performed to examine the stability of the results.

RESULTS: Ten articles were selected, and nine articles were included in the meta-analysis. The results of the meta-analysis showed hospital mortality [OR = 0.65, 95%CI (0.44, 0.95), P = 0.03] and thrombosis events decreased (OR = 0.55, 95%CI [0.37, 0.83], P = 0.004) in bivalirudin group compared with heparin in adult patients. Major bleeding events (OR = 0.66, 95%CI [0.17, 2.55], P = 0.55), ECMO duration (MD = 18.92, 95%CI [-29.33, 67.17], P = 0.44) and circuit intervention events (OR = 1.67, 95%CI [0.54, 5.18], P = 0.37) in the bivalirudin group was not statistically significant compared with the heparin group.

CONCLUSION: Bivalirudin may provide survival benefits and reduce thrombosis in adult patients on ECMO compared with heparin. There is no difference in treating major bleeding events between bivalirudin and heparin group. However, because all included studies were retrospective observational studies, the evidence level of this systematic review is low and heterogeneity could not be avoided. More high-quality clinical studies are urgently needed to confirm these benefits.

PMID:35007937 | DOI:10.1016/j.thromres.2021.12.024

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High glucose increases IGF-2/H19 expression by changing DNA methylation in HTR8/SVneo trophoblast cells

Placenta. 2021 Dec 28;118:32-37. doi: 10.1016/j.placenta.2021.12.022. Online ahead of print.

ABSTRACT

INTRODUCTION: Gestational diabetes mellitus (GDM) is associated with many adverse outcomes of pregnancy, especially macrosomia. The aim of our study was to verify whether high glucose concentrations change the methylation levels of the insulin-like growth factor-2 (IGF-2)/H19 gene promoters to increase the expression of IGF-2, a key gene in fetal growth regulation.

METHODS: HTR8/SVneo cells were used to establish a cell model of intrauterine hyperglycemia in pregnant women with GDM. The RNA expression levels of the IGF-2/H19 genes and the methylation levels of the IGF-2/H19 gene promoter regions were measured. Methylated and unmethylated IGF-2/H19 gene promoter plasmids were transfected into HTR8/SVneo cells.

RESULTS: Among the five groups of cells, the RNA levels of IGF-2 and H19 were lowest in the 5-mM (physiological blood glucose level) group, which was statistically significant (all P < 0.05). Compared with those in the 5-mM group, two cytosine-phosphate-guanine (CpG) sites in the promoter region of the IGF-2 gene and twelve CpG sites in the promoter region of the H19 gene had statistically significant changes in methylation levels (all P < 0.05). Additionally, luciferase activity was significantly higher in cells transfected with the methylated H19 gene promoter plasmid than in control cells transfected with the unmethylated plasmid (P < 0.01), while the methylated IGF-2 gene promoter plasmid produced lower luciferase activity than the unmethylated plasmid (P < 0.01).

DISCUSSION: High glucose concentrations may increase IGF-2/H19 expression by changing the methylation levels of the IGF-2 and H19 gene promoters.

PMID:35007927 | DOI:10.1016/j.placenta.2021.12.022

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The effect of Covid-19 in digital media use of Finnish physicians – Four wave longitudinal panel survey

Int J Med Inform. 2021 Dec 29;159:104677. doi: 10.1016/j.ijmedinf.2021.104677. Online ahead of print.

ABSTRACT

BACKGROUND: Covid-19 pandemic has boosted digitalization in healthcare, as mobility restrictions and social distancing rules have made healthcare providers to adopt digital tools to replace or complement face-to-face interactions.

PURPOSE: We discuss the effects of Covid-19 pandemic on physicians’ use of digital media. We examine whether Covid-19 conditions have changed how physicians use internet resources for information search, how they engage in social media, and their attitude towards online events.

BASIC PROCEDURES: The study was done as a longitudinal panel survey in four waves. The sample was a panel including active physicians in Finland. The panel was updated annually. Identical surveys were administered in 2018, 2019, 2020 and 2021. Spring 2020 was the time when Finland executed mobility restrictions and re-organization of healthcare because of pandemic. Comparing results of the survey before and after Covid-19 restrictions gives us a unique opportunity to do comparative analysis of Covid-19 effects.

MAIN FINDINGS: Our results show that the use of digital media for information search stayed relatively stable without statistically significant change during the four-year period covered in the study. The use of social media rose steadily from 2018 to 2021 with no significant difference in the trend. However, there was a significant change in the attitude of Finnish physicians on online events. Year 2021, the attitude remained in this more positive level.

PRINCIPAL CONCLUSIONS: As use of digital media including social media was already high prior Covid-19 in Finland, our results do not show significant change because of special circumstances introduced in 2020. However, our results show that the attitudes towards online events turned more positive during Covid-19 related restrictions. This could indicate that Covid-19 era has triggered a change that might continue also when pandemic related restrictions will be removed.

PMID:35007925 | DOI:10.1016/j.ijmedinf.2021.104677

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The respond to the COVID-19 pandemic of dental hygienist in South Korea Part Ⅰ. Infection control knowledge and practice

Int J Dent Hyg. 2022 Jan 10. doi: 10.1111/idh.12577. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate infection control knowledge and its practice of clinical dental hygienists in response to Coronavirus Disease 2019 (COVID-19) in South Korea.

METHODS: 9 questions (Q9-K) on the degree of knowledge acquisition of dental hygienists in response to COVID-19, and another 9 questions (Q9-P) on the practices for COVID-19 infection and spread prevention were prepared. From 500 clinical dental hygienists in South Korea, answers about their general characteristics, Q9-K, and Q9-P were collected. 1 point was given to each question based on the ‘yes’ answers from Q9-K and Q9-P, and Score-K and Score-P were calculated, respectively. To identify factors affecting Score-P, multiple linear regression analysis was performed. In all analyses, p-values lower than 0.05 were considered statistically significant.

RESULTS: Average scores of Score-K and Score-P were 7.36±1.35 and 6.26±2.07, respectively. The regression model of Score-P was significant (F=20.788, p<0.001). With respect to Score-P, Score-K (β=0.385), age (β=0.275), dental hospital (β=0.158), monthly income of $2,360∼$2,730 (β=0.104) had a significantly positive correlation, and the total years of career (β=-0.293) are found to have a significantly negative correlation.

CONCLUSIONS: Infection control knowledge and practice of clinical dental hygienists in South Korea was found to be vulnerable in the group of hygienists who are younger than 27 years old, working in dental clinics, and whose monthly income is less than under $2000. Also, the factor that influences infection control practice the most was the degree of knowledge. Therefore, continuous infection control education and supplement targeting these vulnerable groups are necessary.

PMID:35007394 | DOI:10.1111/idh.12577

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Noise-induced versus intrinsic oscillation in ecological systems

Ecol Lett. 2022 Jan 10. doi: 10.1111/ele.13956. Online ahead of print.

ABSTRACT

Studies of oscillatory populations have a long history in ecology. A first-principles understanding of these dynamics can provide insights into causes of population regulation and help with selecting detailed predictive models. A particularly difficult challenge is determining the relative role of deterministic versus stochastic forces in producing oscillations. We employ statistical physics concepts, including measures of spatial synchrony, that incorporate patterns at all scales and are novel to ecology, to show that spatial patterns can, under broad and well-defined circumstances, elucidate drivers of population dynamics. We find that when neighbours are coupled (e.g. by dispersal), noisy intrinsic oscillations become distinguishable from noise-induced oscillations at a transition point related to synchronisation that is distinct from the deterministic bifurcation point. We derive this transition point and show that it diverges from the deterministic bifurcation point as stochasticity increases. The concept of universality suggests that the results are robust and widely applicable.

PMID:35007391 | DOI:10.1111/ele.13956

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Computer extracted features of nuclear morphology in hematoxylin and eosin images distinguish Stage II and IV colon tumors

J Pathol. 2022 Jan 10. doi: 10.1002/path.5864. Online ahead of print.

ABSTRACT

We assessed the utility of quantitative features of colon cancer nuclei, extracted from digitized hematoxylin and eosin-stained whole slide images (WSIs), to distinguish between Stage II from Stage IV colon cancers. Our discovery cohort comprised 100 Stage II and Stage IV colon cancer cases sourced from the University Hospitals Cleveland Medical Center (UHCMC). We performed initial (independent) model validation on 51 (143) Stage II and 79 (54) Stage IV colon cancer cases from UHCMC (The Cancer Genome Atlas’s Colon Adenocarcinoma, TCGA-COAD, cohort). Our approach comprised the following steps, (1) a fully convolutional deep neural network with VGG-18 architecture was trained to locate cancer on WSIs, (2) another deep-learning model based on Mask-RCNN with Resnet-50 architecture was used to segment all nuclei from within the identified cancer region, (3) a total of 26,641 quantitative morphometric features pertaining to nuclear shape, size, and texture were extracted from within and outside tumor nuclei, (4) a random forest classifier was trained to distinguish between Stage II and Stage IV colon cancers using the 5 most discriminatory features selected by the Wilcoxon rank-sum test. Our trained classifier using these top 5 features yielded an AUC of 0.81 and 0.78, respectively, on the held-out cases in UHCMC and TCGA validation sets. For 197 TCGA-COAD cases, the Cox-proportional hazards model yielded a hazard ratio of 2.20 (95% CI: 1.24-3.88) with a concordance index of 0.71 using only top-five features for risk stratification of overall survival. The Kaplan-Meier estimate also showed statistically significant separation between the low-risk and high-risk patients with a log-rank p-value of 0.0097. Finally, unsupervised clustering of the top-five features revealed that Stage IV colon cancers with peritoneal spread were morphologically more similar to Stage II colon cancers with no long-term metastases than Stage IV colon cancers with hematogenous spread. This article is protected by copyright. All rights reserved.

PMID:35007352 | DOI:10.1002/path.5864

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S100-stained perineural invasion is associated with worse prognosis in stage I/II colorectal cancer: Its possible association with immunosuppression in the tumor

Pathol Int. 2022 Jan 10. doi: 10.1111/pin.13195. Online ahead of print.

ABSTRACT

Perineural invasion (PNI) is known as a poor prognostic factor in colorectal cancer (CRC). Although histopathological evaluation of PNI is usually conducted on hematoxylin and eosin (HE)-stained sections (HE-PNI), it remains controversial whether PNI can be precisely evaluated only by HE-staining, and its concise mechanisms causing worse prognosis remains elusive. In this study, we examined the impact of PNI evaluated by S-100-immunostaining (S100-PNI) on postoperative mortality in 279 consecutive CRC patients and further investigated its association with the tumor immune microenvironment. S100-PNI was present in 67.3% of tumors whereas HE-PNI was present in 18.5%. A 5-year cumulative incidence of death in the S100-PNI-positive group was significantly higher than that in the S100-PNI-negative group. Further statistical analyses revealed that S100-PNI was an independent prognostic factor of all-cause mortality in stage I/II but not in stage III/IV. Importantly, S100-PNI was associated with the altered tumor immune microenvironment. Infiltrating immune cell profiling revealed that stromal lymphocytic reaction, which was inversely correlated with postoperative mortality, was significantly reduced in S100-PNI-positive tumors compared to S100-PNI-negative tumors in stage I/II. These results indicated that S100-PNI was a poor prognostic factor in stage I/II CRC with possible association with immunosuppression in the tumor.

PMID:35007380 | DOI:10.1111/pin.13195

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Microwave Ablation versus Laparoscopic Resection as First-line Therapy for Solitary 3-5 cm Hepatocellular Carcinoma

Hepatology. 2022 Jan 10. doi: 10.1002/hep.32323. Online ahead of print.

ABSTRACT

The study objective was to compare the effectiveness of microwave ablation (MWA) and laparoscopic liver resection (LLR) on solitary 3-5cm HCC over time. From 2008 to 2019, 1,289 patients from 12 hospitals were enrolled in this retrospective study. Diagnosis of all lesions were based on histopathology. Propensity score matching (PSM) was used to balance all baseline variables between the two groups in 2008-2019 (n =335 in each group) and 2014-2019 (n =257 in each group) cohorts, respectively. For cohort 2008-2019, during a median follow-up of 35.8 months, there were no differences in overall survival (OS) between MWA and LLR (Hazard ratio (HR): 0.88, 95% confidence interval (CI) 0.65-1.19, P =0.420), and MWA was inferior to LLR regarding disease-free survival (DFS) (HR 1.36, 95%CI (1.05-1.75), P =0.017). For cohort 2014-2019, there was comparable OS (HR 0.85, 95%CI (0.56-1.30), P =0.460) and approached statistical significance for DFS (HR 1.33, 95%CI (0.98-1.82), P =0.071) between MWA and LLR. Subgroup analyses showed comparable OS in 3.1-4.0cm HCCs (HR 0.88, 95%CI (0.53-1.47), P =0.630) and 4.1-5.0cm HCCs (HR 0.77, 95%CI (0.37-1.60), P =0.483) between two modalities. For both cohorts, MWA shared comparable major complications (both P >0.05), shorter hospitalization and lower cost to LLR (all P <0.001). Conclusion: MWA might be a first-line alternative to LLR for solitary 3-5cm HCC in selected patients with technical advances, especially for patients unsuitable for LLR.

PMID:35007334 | DOI:10.1002/hep.32323

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Prevention adopted by healthcare workers within their families in the Covid-19 pandemic

Rev Esc Enferm USP. 2022 Jan 7;56:e20210330. doi: 10.1590/1980-220X-REEUSP-2021-0330. eCollection 2022.

ABSTRACT

OBJECTIVE: To identify factors associated with the adoption of non-pharmacological preventive measures against covid-19 by healthcare workers within their families.

METHOD: This is an analytical cross-sectional study carried out from October 1st to December 31st, 2020, with 11,513 healthcare workers in Brazil. Data collection through a virtual questionnaire on the platform Survey Monkey. To characterize the participants, descriptive statistical analysis was used with measures of absolute and relative frequency. Using inferential statistics, independent variables and outcome were compared, with hypothesis tests for association (chi-square, Fisher’s exact test), logistic regression, and Woe analysis. A significance level of 95% was used.

RESULTS: Most workers used measures such as hand hygiene, environmental sanitation, food hygiene, use of fabric masks, and physical distancing from family members. The association among variables was significant for the region, especially the South region, female sex, and nursing professionals.

CONCLUSION: Healthcare workers adopt preventive measures against covid-19 within family life, especially the women and nursing professionals, with family isolation being the measure of greatest adherence.

PMID:35007318 | DOI:10.1590/1980-220X-REEUSP-2021-0330

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Cytotoxicity-related gene expression and chromatin accessibility define a subset of CD4+ T cells that mark progression to type 1 diabetes

Diabetes. 2022 Jan 7:db210612. doi: 10.2337/db21-0612. Online ahead of print.

ABSTRACT

Type 1 diabetes in children is heralded by a preclinical phase defined by circulating autoantibodies to pancreatic islet antigens. How islet autoimmunity is initiated and then progresses to clinical diabetes remains poorly understood. Only one study has reported gene expression in specific immune cells of at-risk children, associated with progression to islet autoimmunity. We analysed gene expression by RNAseq in CD4+ and CD8+ T cells, NK cells and B cells, and chromatin accessibility by ATACseq in CD4+ T cells, in five genetically at-risk children with islet autoantibodies who progressed to diabetes over a median of 3 years (‘Progressors’) compared to five children matched for sex, age and HLA-DR who had not progressed (‘Non-progressors). In Progressors, differentially expressed genes (DEGs) were largely confined to CD4+ T cells and enriched for cytotoxicity-related genes/pathways. Several top-ranked DEGs were validated in a semi-independent cohort of 13 Progressors and 11 Non-progressors. Flow cytometry confirmed progression was associated with expansion of CD4+ cells with a cytotoxic phenotype. By ATAC-seq, progression was associated with reconfiguration of regulatory chromatin regions in CD4+ T cells, some linked to differentially expressed cytotoxicity-related genes. Our findings suggest that cytotoxic CD4+ T cells play a role in promoting progression to type 1 diabetes.

PMID:35007320 | DOI:10.2337/db21-0612