Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

The Age-AST-D Dimer (AAD) Regression Model Predicts Severe COVID-19 Disease

Aim. Coronavirus disease (COVID-19) ranges from mild clinical phenotypes to life-threatening conditions like severe acute respiratory syndrome (SARS). It has been suggested that early liver injury in these patients could be a risk factor for poor outcome. We aimed to identify early biochemical predictive factors related to severe disease development with intensive care requirements in patients with COVID-19. Methods. Data from COVID-19 patients were collected at admission time to our hospital. Differential biochemical factors were identified between seriously ill patients requiring intensive care unit (ICU) admission (ICU patients) versus stable patients without the need for ICU admission (non-ICU patients). Multiple linear regression was applied, then a predictive model of severity called Age-AST-D dimer (AAD) was constructed (n=166) and validated (n=170). Results. Derivation cohort: from 166 patients included, there were 27 (16.3%) ICU patients that showed higher levels of liver injury markers (P<0.01) compared with non-ICU patients: alanine aminotrasnferase (ALT) 225.4±341.2 vs. 41.3±41.1, aspartate aminotransferase (AST) 325.3±382.4 vs. 52.8±47.1, lactic dehydrogenase (LDH) 764.6±401.9 vs. 461.0±185.6, D-dimer (DD) 7765±9109 vs. 1871±4146, and age 58.6±12.7 vs. 49.1±12.8. With these finding, a model called Age-AST-DD (AAD), with a cut-point of <2.75 (sensitivity=0.797 and specificity=0.391, c−statistic=0.74; 95%IC: 0.62-0.86, P<0.001), to predict the risk of need admission to ICU (OR=5.8; 95% CI: 2.2-15.4, P=0.001), was constructed. Validation cohort: in 170 different patients, the AAD model<2.75 (c−statistic=0.80 (95% CI: 0.70-0.91, P<0.001) adequately predicted the risk (OR=8.8, 95% CI: 3.4-22.6, P<0.001) to be admitted in the ICU (27 patients, 15.95%). Conclusions. The elevation of AST (a possible marker of early liver injury) along with DD and age efficiently predict early (at admission time) probability of ICU admission during the clinical course of COVID-19. The AAD model can improve the comprehensive management of COVID-19 patients, and it could be useful as a triage tool to early classify patients with a high risk of developing a severe clinical course of the disease

Evidence of human occupation in Mexico around the Last Glacial Maximum.

The initial colonization of the Americas remains a highly debated topic1, and the exact timing of the first arrivals is unknown. The earliest archaeological record of Mexico-which holds a key geographical position in the Americas-is poorly known and understudied. Historically, the region has remained on the periphery of research focused on the first American populations2. However, recent investigations provide reliable evidence of a human presence in the northwest region of Mexico3,4, the Chiapas Highlands5, Central Mexico6 and the Caribbean coast7-9 during the Late Pleistocene and Early Holocene epochs. Here we present results of recent excavations at Chiquihuite Cave-a high-altitude site in central-northern Mexico-that corroborate previous findings in the Americas10-17of cultural evidence that dates to the Last Glacial Maximum (26,500-19,000 years ago)18, and which push back dates for human dispersal to the region possibly as early as 33,000-31,000 years ago. The site yielded about 1,900 stone artefacts within a 3-m-deep stratified sequence, revealing a previously unknown lithic industry that underwent only minor changes over millennia. More than 50 radiocarbon and luminescence dates provide chronological control, and genetic, palaeoenvironmental and chemical data document the changing environments in which the occupants lived. Our results provide new evidence for the antiquity of humans in the Americas, illustrate the cultural diversity of the earliest dispersal groups (which predate those of the Clovis culture) and open new directions of research

Overexpression of <i>MEOX2</i> and <i>TWIST1</i> Is Associated with H3K27me3 Levels and Determines Lung Cancer Chemoresistance and Prognosis

<div><p>Lung cancer is the leading cause of death from malignant diseases worldwide, with the non-small cell (NSCLC) subtype accounting for the majority of cases. NSCLC is characterized by frequent genomic imbalances and copy number variations (CNVs), but the epigenetic aberrations that are associated with clinical prognosis and therapeutic failure remain not completely identify. In the present study, a total of 55 lung cancer patients were included and we conducted genomic and genetic expression analyses, immunohistochemical protein detection, DNA methylation and chromatin immunoprecipitation assays to obtain genetic and epigenetic profiles associated to prognosis and chemoresponse of NSCLC patients. Finally, siRNA transfection-mediated genetic silencing and cisplatinum cellular cytotoxicity assays in NSCLC cell lines A-427 and INER-37 were assessed to describe chemoresistance mechanisms involved. Our results identified high frequencies of CNVs (66–51% of cases) in the 7p22.3–p21.1 and 7p15.3–p15.2 cytogenetic regions. However, overexpression of genes, such as <i>MEOX2</i>, <i>HDAC9</i>, <i>TWIST1</i> and <i>AhR</i>, at 7p21.2–p21.1 locus occurred despite the absence of CNVs and little changes in DNA methylation. In contrast, the promoter sequences of <i>MEOX2</i> and <i>TWIST1</i> displayed significantly lower/decrease in the repressive histone mark H3K27me3 and increased in the active histone mark H3K4me3 levels. Finally these results correlate with poor survival in NSCLC patients and cellular chemoresistance to oncologic drugs in NSCLC cell lines in a <i>MEOX2</i> and <i>TWIST1</i> overexpression dependent-manner. In conclusion, we report for the first time that <i>MEOX2</i> participates in chemoresistance irrespective of high CNV, but it is significantly dependent upon H3K27me3 enrichment probably associated with aggressiveness and chemotherapy failure in NSCLC patients, however additional clinical studies must be performed to confirm our findings as new probable clinical markers in NSCLC patients.</p></div

Outcomes clinical data of NSCLC patients.

<p>(AD) Adenocarcinoma Patients; (N.D.) Not Detected; and (N.A.) Not Applied.</p><p>Outcomes clinical data of NSCLC patients.</p

Genome-wide analysis of normal lung and paired tumors.

<p>Focal analysis of the whole genome and chromosome 7. (A) A whole-genome amplification and a bioinformatics segmental analysis of three lung cancer patients was conducted using matched, histologically adjacent non-involved lung tissue (LNAT) and lung carcinomas (LT). (B) Whole-genome and focal analyses of normal lung, lung precursor lesions and lung carcinomas (18–14 of 27 lung lesions with high CNV). (C) A focal analysis of chromosome 7 revealed a high frequency of CNV at region 7p21 (arrow) in precursor lung lesions and lung carcinomas.</p

Histone modification profile at the <i>MEOX2</i> and <i>TWIST1</i> promoters under baseline conditions and after cisplatinum treatment in NSCLC cell lines (A-427 and INER-37).

<p>(A) <i>MEOX2</i> histone profile under baseline conditions. (B) <i>MEOX2</i> histone modification profile changes after cisplatinum treatment. (C) <i>TWIST1</i> histone profile under baseline conditions. (D) <i>TWIST1</i> histone modification profile changes after cisplatinum treatment. (E) <i>MEOX2</i> mRNA expression induction by cisplatinum stimulation as compared to the baseline conditions from both NSCLC cell lines. (F) <i>TWIST1</i> mRNA expression induction by cisplatinum stimulation as compared to the baseline conditions from both NSCLC cell lines. (G) Chemoresistance curves evaluating cellular viability for both NSCLC cell lines. (H) <i>MEOX2</i> and <i>TWIST1</i> siRNA silencing assays and cellular viability analyses. Statistically significant differences with respect to the baseline control conditions as assessed using an unpaired t-test, *<i>p</i>≤0.05 and **<i>p</i>≤0.001. Error bars represent standard errors of the mean of three technical replicates.</p