Methods:We performed a systematic literature review with meta-analysis, using three databases to assess clinical, laboratory, imaging features, and outcomes of COVID-19 confirmed cases. Observational studies and also case reports, were included, and analyzed separately. We performed a random-effects model meta-analysis to calculate the pooled prevalence and 95% confidence interval (95%CI).Results: 660 articles were retrieved for the time frame (1/1/2020-2/23/2020). After screening, 27 articles were selected for full-text assessment, 19 being finally included for qualitative and quantitative analyses. Additionally, 39 case report articles were included and analyzed separately. For 656 patients, fever (88.7%, 95%CI 84.5-92.9%), cough (57.6%, 40.8-74.4%) and dyspnea (45.6%, 10.9-80.4%) were the most prevalent manifestations. Among the patients, 20.3% (95%CI 10.0-30.6%) required intensive care unit (ICU), 32.8% presented with acute respiratory distress syndrome (ARDS) (95%CI 13.7-51.8), 6.2% (95%CI 3.1-9.3) with shock. Some 13.9% (95%CI 6.2-21.5%) of hospitalized patients had fatal outcomes (case fatality rate, CFR).Conclusion: COVID-19 brings a huge burden to healthcare facilities, especially in patients with comorbidities. ICU was required for approximately 20% of polymorbid, COVID-19 infected patients and hospitalization was associated with a CFR of over 13%. As this virus spreads globally, countries need to urgently prepare human resources, infrastructure and facilities to treat severe COVID-19.

Introduction: An epidemic of Coronavirus Disease 2019 (COVID-19) begun in December 2019 in China, causing a Public Health Emergency of International Concern. Among raised questions, clinical, laboratory, and imaging features have been partially characterized in some observational studies. No systematic reviews have been published on this matter. Methods: We performed a systematic literature review with meta-analysis, using three databases to assess clinical, laboratory, imaging features, and outcomes of COVID-19 confirmed cases. Observational studies, and also case reports, were included and analyzed separately. We performed a random-effects model meta-analysis to calculate the pooled prevalence and 95% confidence interval (95%CI). Results: 660 articles were retrieved (1/1/2020-2/23/2020). After screening by abstract/title, 27 articles were selected for full-text assessment. Of them, 19 were finally included for qualitative and quantitative analyses. Additionally, 39 case report articles were included and analyzed separately. For 656 patients, fever (88.7%, 95%CI 84.5-92.9%), cough (57.6%, 40.8-74.4%) and dyspnea (45.6%, 10.9-80.4%) were the most prevalent manifestations. Among the patients, 20.3% (95%CI 10.0-30.6%) required intensive care unit (ICU), with 32.8% presenting acute respiratory distress syndrome (ARDS) (95%CI 13.7-51.8), 6.2% (95%CI 3.1-9.3) with shock and 13.9% (95%CI 6.2-21.5%) of hospitalized patients with fatal outcomes (case fatality rate, CFR).Conclusion: COVID-19 brings a huge burden to healthcare facilities, especially in patients with comorbidities. ICU was required for approximately 20% of polymorbid, COVID-19 infected patients and this group was associated with a CFR of over 13%. As this virus spreads globally, countries need to urgently prepare human resources, infrastructure, and facilities to treat severe COVID-19.

The erythropoietin-producing hepatocellular (EPH)A2 receptor, tyrosine kinase, is overexpressed and phosphorylated in several types of human tumors and has been associated with malignant transformation. A recent report, however, indicated that stimulation of the EPHA2 receptor ligand, ephrinA1 (EFNA1), inhibits the growth of EPHA2-expressing breast cancer. The authors examined the expression of EPHA2 and EFNA1 using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) in four gastric cancer cell lines and 49 primary gastric cancer samples, as well as in normal gastric tissue. EPHA2 was more highly expressed in tumor tissue than in normal tissue in 27 cases (55%). EFNA1 was overexpressed in tumor tissue in 28 cases (57%). No significant correlation was detected between the expression levels and histologic features such as tumor size, age, vessel invasion, or lymph node involvement. However, EPHA2 overexpression was more prominent in macroscopic type 3 and 4 tumors than in type 1 or 2 advanced gastric cancer. The authors observed EPHA2 expression in three of the four gastric cancer cell lines (AGS, KATO3, and MKN74) that were examined. In one cell line, TMK1, EPHA2 expression was barely detectable using northern blotting, RT-PCR, and western blotting. In contrast, EFNA1 was detected in all cell lines. In the gastric cancer cell lines that endogenously expressed EPHA2, stimulation with ephrinA1-Fc led to decreased EPHA2 protein expression and increased EPHA2 phosphorylation. Finally, the growth of T he erythropoietin-producing hepatocellular (EPH ) receptors represent the largest known family of receptor tyrosine kinases and are activated by interaction with the cell-surface ligands, ephrins (EFN). There is evidence to suggest that some members of the EPH family and their EFN ligands are involved in angiogenesis and oncogenesis through cell adhesion, morphogenesis, capillary sprouting, and chemoattraction.(1−5) EPH receptors have been classified into two subfamilies, EPHA and EPHB. EPHA receptors bind mainly to glycosylphosphatidylinositolanchored EFNA ligands, and EPHB receptors bind to transmembrane EFNB ligands. The expression of EPH family transcripts has been documented in some melanomas and carcinomas.(6,7) Overexpression of EPHA2 is believed to be sufficient to confer malignant/tumorigenic potential on nontransformed mammary epithelial cells.(8) Esophageal squamous cell carcinomas that overexpress EFNA2 have a poorer prognosis than those that do not. (9)

Evidence suggests that the erythropoietin-producing hepatocellular (EPH) receptor tyrosine kinases (RTKs) and their ephrin (EFN) ligands are involved in human carcinogenesis. Expression of two of them, EFNA1 ligand and its receptor, EPHA2, has been proposed to contribute to tumor-induced neovascularization. Colorectal cancers were examined for expressions of EPHA2 and its ligand EFNA1 by semi-quantitative RT-PCR, and double-immunostained for EPHA2 and CD34. Microvessels in the tumors were counted. Double-staining was also performed in 25 cases of adenoma with focal cancer for comparison. Trends of overexpression of both EPHA2 and EFNA1 was found in tumor tissue compared to the corresponding normal tissue in the same specimen [22/37 (59.5%) and 25/37 (67.5%), respectively; P = = = =0.100 for EPHA2 and eceptor tyrosine kinases (RTKs), which are often the products of transforming oncogenes, have been widely implicated in the generation and progression of common human tumors.1) The erythropoietin-producing hepatocellular (EPH) receptors represent the largest known family of RTKs and they are activated by interaction with cell-surface ligands, termed ephrins (EFNs). EPH receptors have been classified into two subfamilies, EPHA and EPHB, according to their preference for either glycosylphosphatidylinositol (GPI)-anchored EFNA ligands or transmembrane EFNB ligands, and 14 receptors and eight ligands have been identified in vertebrates thus far. The EPH family receptor kinases and their EFN ligands are well known to be involved in fundamental developmental processes of the nervous system, including axon guidance, 2) axon fasciculation,3) neural crest cell migration, 4) acquisition of brain subregional identity, 5) and neuronal cell survival. 6) Evidence has suggested that one member of the EPH family, EPHA2, and one of its ligands EFNA1, are associated with tumorigenesis and tumor neovascularization. 7,8) For example, forced overexpression of EPHA2 causes tumorigenesis by mammary epithelial cells in vitro, and its ligand, EFNA1, has been found to involved in TNF-α-induced angiogenesis.7, 9) A recent paper reported that EFNA1 ligand and its receptor, EPHA2, are expressed by human breast cancer cells and human Kaposi's sarcoma cells during tumor neovascularization. 10) However, expression of EPH receptors and EFNs in gastrointestinal tract tumors has seldom been documented.In this study, we investigated the expression of EPHA2 and its ligand, EFNA1, in colorectal cancer specimens by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis and we counted CD34-positive microvessels surrounding the tumors to identify the relation between colorectal cancer and the EPHA2/EFNA1 system in terms of microvessel induction. Materials and MethodsTissues. RT-PCR samples of human colorectal cancer specimens and corresponding normal tissue were obtained from surgical resections performed at the Hamamatsu University School of Medicine between 1999 and 2002. The clinicopathological characteristics of 37 colorect...

A significant reduction of EphA7 expression in human colorectal cancers was shown using semiquantitative reverse transcription-polymerase chain reaction analysis in 59 colorectal cancer tissues, compared to corresponding normal mucosas (P ¼ 0.008), and five colon cancer cell lines. To investigate the mechanism of EphA7 downregulation in colorectal cancer, we examined the methylation status of the 5 0 CpG island around the translation start site in five colon cancer cell lines using restriction enzymes, methylation-specific PCR, and bisulfite sequencing and found evidence of aberrant methylation. The expression of EphA7 in colon cancer cell lines was restored after treatment with 5-aza-2 0 -deoxycytidine. Analysis of methylation status in totally 75 tumors compared to clinicopathological parameters revealed that hypermethylation of colorectal cancers was more frequent in male than in female (P ¼ 0.0078), and in moderately differentiated than in well-differentiated adenocarcinomas (P ¼ 0.0361). There was a tendency that hypermethylation in rectal cancers was more frequent than in colon cancers (P ¼ 0.0816). Hypermethylation was also observed in colorectal adenomas. This is the first report describing the downregulation of an Eph family gene in a solid tumor via aberrant 5 0 CpG island methylation. It provides the evidence that EphA7 gene is involved in human colorectal carcinogenesis.