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Background: Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is one of the ultimate treatments for acute respiratory failure. However, the effectiveness of ECMO in patients with novel coronavirus disease (COVID-19) is unknown.Case Presentation: A 72-year-old woman who was a passenger of a cruise ship tested positive for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) while in quarantine on board using throat swab. Three days after admission, her condition deteriorated, and she was subsequently intubated. On day 6, VV-ECMO was introduced. Lopinavir/ritonavir was given; continuous renal replacement therapy was also introduced. On day 10, her chest radiography and lung compliance improved. She was weaned off ECMO on day 12.Conclusion: Treatment of severe pneumonia in COVID-19 by ECMO should recognize lung plasticity considering time to ECMO introduction and interstitial biomarkers. In Japan, centralization of ECMO patients has not been sufficient. Thus, we suggest nationwide centralization and further research to respond to the crisis caused by COVID-19.

Cyclooxygenase (COX)-2 is known to correlate with poor cancer prognosis and to contribute to tumor metastasis. However, the precise mechanism of this phenomenon remains unknown. We have previously reported that host stromal prostaglandin E 2 (PGE 2 )-prostaglandin E2 receptor (EP)3 signaling appears critical for tumor-associated angiogenesis and tumor growth. Here we tested whether the EP3 receptor has a critical role in tumor metastasis. Lewis lung carcinoma (LLC) cells were intravenously injected into WT mice and mice treated with the COX-2 inhibitor NS-398. The nonselective COX inhibitor aspirin reduced lung metastasis, but the COX-1 inhibitor SC560 did not. The expression of matrix metalloproteinases (MMP)-9 and vascular endothelial growth factor (VEGF)-A was suppressed in NS-398-treated mice compared with PBS-treated mice. Lungs containing LLC colonies were markedly reduced in EP3 receptor knockout (EP3 )/) ) mice compared with WT mice. The expression of MMP-9 and VEGF-A was downregulated in metastatic lungs of EP3 )/) mice. An immunohistochemical study revealed that MMP-9-expressing endothelial cells were markedly reduced in EP3 )/) mice compared with WT mice. When HUVEC were treated with agonists for EP1, EP2, EP3, or EP4, only the EP3 agonist enhanced MMP-9 expression. These results suggested that EP3 receptor signaling on endothelial cells is essential for the MMP-9 upregulation that enhances tumor metastasis and angiogenesis. An EP3 receptor antagonist may be useful to protect against tumor metastasis. (Cancer Sci 2009; 100: 2318-2324 M etastasis is the primary cause of mortality in cancer patients.(1) While it has been recognized that the movement of neoplastic cells is not a random process, the molecular and cellular mechanisms governing their movement, survival through foreign tissue, and parameters for selection of their final destination remain unclear. To produce clinically relevant lesions, metastatic cells must complete the following steps, involving: the ability of tumor cells to escape from their original position, to attach to the extracellular matrix (ECM), to degrade the ECM component, and to migrate through these ECM. Thus, both cell-cell adhesion and ECM degradation represent significant barriers to the metastasis of tumor cells. Nonsteroidal anti-inflammatory drugs (NSAID), which block the enzyme activity of cyclooxygenase (COX), have been widely used for anti-inflammatory and analgesic purposes. Several papers have reported that a significant reduction in mortality from colorectal cancer occurred depending on the cumulative doses of an NSAID, but on the other hand further evidence suggests that NSAID also affect the incidence and progression of other types of cancer, pointing to a possible role of COX in other types of tumor formation. (3)(4)(5) Prostaglandins comprise a large family of small lipid molecules derived from COX-1-and COX-2-mediated metabolism of arachidonic acid to prostaglandin G 2 (PGG 2 ) ⁄ prostaglandin H 2 (H 2 ).(6) Cell-specific prostaglandin synthases convert pros...

The long-term exercise capacity of coronavirus disease 2019 patients with acute respiratory distress syndrome is not clear. The 6-min walking distance of four patients with coronavirus disease 2019–associated acute respiratory distress syndrome was followed for 6 mos after admission to the hospital. These four patients were admitted to the intensive care unit of our hospital and received mechanical ventilation. Rehabilitation therapy (positioning, postural drainage, and passive range-of-motion exercises) was started after intensive care unit admission. Mobilization therapy, including muscle power training, sitting on the edge of the bed, and endurance training, was performed after the end of sedation. The Medical Research Council sum scores and Barthel Indexes for the patients improved after intensive care unit discharge and completely recovered 6 mos after admission to the hospital. However, the 6-min walking distance of the four patients remained shorter than those of healthy persons of the same age at 6 mos after admission to the hospital. Furthermore, the minimum Spo 2 during the 6-min walking test remained less than 96%. It is possible that patients who receive mechanical ventilation due to coronavirus disease 2019–associated acute respiratory distress syndrome have decreased long-term exercise capacity, despite muscle power and activities of daily living recovering completely.

Primary primitive neuroectodermal tumor (PNET) of the female genital tract is rare, and its proper classification remains unclear. The clinical, histologic, and immunophenotypic features as well as EWSR1 rearrangement status of 19 gynecologic PNETs, including 10 ovarian, 8 uterine, and 1 vulvar tumors, are herein reported. Patient age ranged from 12 to 68 years, with a median age of 20 and 51 years among those with ovarian and uterine PNETs, respectively. Morphologic features of central nervous system (CNS) tumors were seen in 15 PNETs, including 9 medulloblastomas, 3 ependymomas, 2 medulloepitheliomas, and 1 glioblastoma, consistent with central PNET. The remaining 4 PNETs were composed entirely of undifferentiated small round blue cells and were classified as Ewing sarcoma/peripheral PNET. Eight PNETs were associated with another tumor type, including 5 ovarian mature cystic teratomas, 2 endometrial low-grade endometrioid carcinomas and a uterine carcinosarcoma. By immunohistochemistry, 17 PNETs expressed at least 1 marker of neuronal differentiation, including synaptophysin, NSE, CD56, S100, and chromogranin in 10, 8, 14, 8, and 1 tumors, respectively. GFAP was positive in 4 PNETs, all of which were of central type. Membranous CD99 and nuclear Fli-1 staining was seen in 10 and 16 tumors, respectively, and concurrent expression of both markers was seen in both central and Ewing sarcoma/peripheral PNETs. All tumors expressed vimentin; while keratin cocktail (CAM5.2, AE1/AE3) staining was only focally present in 4 PNETs. Fluorescence in situ hybridization was successful in all cases and confirmed EWSR1 rearrangement in 2 of 4 tumors demonstrating morphologic features of Ewing sarcoma/peripheral PNET and concurrent CD99 and Fli-1 expression. In conclusion, central and Ewing sarcoma/peripheral PNETs may be encountered in the female genital tract with central PNETs being more common. Central PNETs show a spectrum of morphologic features that overlaps with CNS tumors but lack EWSR1 rearrangements. GFAP expression supports a morphologic impression of central PNET and is absent in Ewing sarcoma/peripheral PNET. Ewing sarcoma/peripheral PNETs lack morphologic features of CNS tumors.

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that leads to severe respiratory failure (RF). It is known that host exposure to viral infection triggers an iron-lowering response to mitigate pathogenic load and tissue damage. However, the association between host iron-lowering response and COVID-19 severity is not clear. This two-center observational study of 136 adult hospitalized COVID-19 patients analyzed the association between disease severity and initial serum iron, total iron-binding capacity (TIBC), and transferrin saturation (TSAT) levels. Serum iron levels were significantly lower in patients with mild RF than in the non-RF group; however, there were no significant differences in iron levels between the non-RF and severe RF groups, depicting a U-shaped association between serum iron levels and disease severity. TIBC levels decreased significantly with increasing severity; consequently, TSAT was significantly higher in patients with severe RF than in other patients. Multivariate analysis including only patients with RF adjusted for age and sex demonstrated that higher serum iron and TSAT levels were independently associated with the development of severe RF, indicating that inadequate response to lower serum iron might be an exacerbating factor for COVID-19.

Thromboxane A 2 (TXA 2 ) is a prostanoid formed by thromboxane synthase using the cyclooxygenase product, prostaglandin H(2), as the substrate. TXA 2 was shown to enhance tumor metastasis, but the underlying mechanism remains unclear. B16F1 melanoma cells were intravenously injected into TXA 2 receptor (TP) knockout mice (TP À/À ) and wild-type littermates (WT). TP À/À showed a reduction in B16F1 lung colonization and mortality rate, which were associated with a decreased number of platelets. Platelet activation as assessed by P-selectin expression was suppressed in TP À/À . A selective P-selectin neutralizing antibody decreased the lung colonization in WT mice, but not in TP. The expression of P-selectin glycoprotein ligand-1 in B16F1 and HUVEC were enhanced by treatment with U46619, a thromboxane analog. The plasma levels of vascular endothelial growth factor (VEGF) and stromal-derived factor (SDF)-1 were lower in TP À/À . In TPÀ/À, the mobilization of progenitor cells expressing CXCR4 + VEGFR1+ from bone marrow and the recruitment of those cells to lung tissues were suppressed. These results suggest that TP signaling plays a critical role in tumor colonization through P-selectin-mediated interactions between platelets-tumor cells and tumor cells-endothelial cells through the TP signaling-dependent production of VEGF and SDF-1, which might be involved in the mobilization of VEGFR1 + CXCR4 + cells. Blockade of TP signaling might be useful in the treatment of tumor metastasis. (Cancer Sci 2012; 103: 700-707) T umor metastasis is responsible for over 90% of cancerassociated mortality, yet the mechanism of tumor metastasis remains poorly understood. Tumor metastasis to distant tissues depends on interactions between tumor cells and the host microenvironment within the circulation and target tissues. This involves blood cells, components of the coagulation system, stromal cells and the extracellular matrix. Cells within the microvasculature that contribute to metastasis are endothelial cells, platelets, lymphocytes, macrophages, fibroblasts and bone marrow-derived progenitor cells.(1)Platelets have been implicated in the development of tumor metastasis.(2-6) Thrombocytosis has been associated with advanced, often metastatic, stages of cancer and with poor prognosis in a variety of tumors. Suppression of platelet-tumor cell association by antiplatelet agents or anticoagulants potently inhibits experimental metastasis. (7,8) Interactions between platelets and tumor cells facilitate tumor cell arrest at the endothelium and assist tumor cell survival within the bloodstream, with the subsequent formation of experimental metastasis.(3,9) The platelet-tumor cell and tumor cells-endothelial cells aggregates might supply tumor cells with critical stimulatory growth factors and cytokines, which are released on platelet activation. (10,11) Thromboxane A 2 (TXA 2 ) is a potent stimulator of platelet activation and aggregation, and of vascular constriction, and exerts its biological activity by binding to a G protein-coupled...

These results indicated that TP signalling facilitates ischaemia-induced angiogenesis via P-selectin-mediated platelet adhesion to PSGL-1 on the ECs at ischaemic sites and the supply of pro-angiogenic factors by the adherent platelets.