Retroperitoneal hemorrhage with COVID-19

Introduction: Early prophylactic administration of anticoagulants is recommended in patients with coronavirus disease 2019 (COVID-19). A case of retroperitoneal hemorrhage during inpatient treatment for COVID-19 is reported. Case Presentation : A 69-year-old man was diagnosed with COVID-19 6 days after symptom onset. After admission for difficulty of breathing, he was treated with steroid pulse therapy, remdesivir, and heparin sodium. On day 16 after admission, his hemoglobin and blood pressure dropped. Computed tomography showed a left retroperitoneal hematoma and multiple areas of extravasation in bilateral iliopsoas muscles. Anticoagulation therapy was stopped, and blood transfusion therapy was chosen by considering poor general condition caused by severe pneumonia. On day 19, the hemoglobin and blood pressure improved, and blood transfusion was stopped. However, he died on day 25 due to pneumonia. Conclusion : When retroperitoneal hemorrhage occurs as a complication of COVID-19, appropriate treatment decision, transcatheter arterial embolization or conservative treatment, should be chosen based on patient’s condition

Significant response of sunitinib for RCC

Introduction: A case of multiple liver metastases of clear cell RCC with a significant response to sunitinib as the fifth line after nivolumab is reported. Case presentation: The patient was a 65-year-old man who underwent open nephrectomy for RCC. After the nephrectomy, he had recurrences several times, and metastasectomy had been performed for each recurrence. At 13 years after the nephrectomy, multiple liver, and lung metastases appeared. The treatment was switched to axitinib, followed by cabozantinib, then nivolumab. The best response was PR, SD, and PD for these three drugs, and treatment duration was 14, 3, and 3 months, respectively. As the fifth line, sunitinib was administered, with significant shrinkage of the multiple liver metastases, and PR has been maintained for 34 months. Conclusion: Sunitinib after an IO-drug showed a significant effect in spite of only slight efficacy with other VEGFR-TKIs, which may have occurred through the alteration of the immunological microenvironment

Biosynthetic Pathway and Genes of Chitin/Chitosan-Like Bioflocculant in the Genus Citrobacter

Chitin/chitosan, one of the most abundant polysaccharides in nature, is industrially produced as a powder or flake form from the exoskeletons of crustaceans such as crabs and shrimps. Intriguingly, many bacterial strains in the genus Citrobacter secrete a soluble chitin/chitosan-like polysaccharide into the culture medium during growth in acetate. Because this polysaccharide shows strong flocculation activity for suspended solids in water, it can be used as a bioflocculant (BF). The BF synthetic pathway of C. freundii IFO 13545 is expected from known bacterial metabolic pathways to be as follows: acetate is metabolized in the TCA cycle and the glyoxylate shunt via acetyl-CoA. Next, fructose 6-phosphate is generated from the intermediates of the TCA cycle through gluconeogenesis and enters into the hexosamine synthetic pathway to form UDP-N-acetylglucosamine, which is used as a direct precursor to extend the BF polysaccharide chain. We conducted the draft genome sequencing of IFO 13545 and identified all of the candidate genes corresponding to the enzymes in this pathway in the 5420-kb genome sequence. Disruption of the genes encoding acetyl-CoA synthetase and isocitrate lyase by homologous recombination resulted in little or no growth on acetate, indicating that the cell growth depends on acetate assimilation via the glyoxylate shunt. Disruption of the gene encoding glucosamine 6-phosphate synthase, a key enzyme for the hexosamine synthetic pathway, caused a significant decrease in flocculation activity, demonstrating that this pathway is primarily used for the BF biosynthesis. A gene cluster necessary for the polymerization and secretion of BF, named bfpABCD, was also identified for the first time. In addition, quantitative RT-PCR analysis of several key genes in the expected pathway was conducted to know their expression in acetate assimilation and BF biosynthesis. Based on the data obtained in this study, an overview of the BF synthetic pathway is discussed

Recurrent multiple liver metastases of clear cell renal cell carcinoma with a significant response to sunitinib after nivolumab treatment

Introduction: A case of multiple liver metastases of clear cell RCC with a significant response to sunitinib as the fifth line after nivolumab is reported. Case presentation: The patient was a 65-year-old man who underwent open nephrectomy for RCC. After the nephrectomy, he had recurrences several times, and metastasectomy had been performed for each recurrence. At 13 years after the nephrectomy, multiple liver, and lung metastases appeared. The treatment was switched to axitinib, followed by cabozantinib, then nivolumab. The best response was PR, SD, and PD for these three drugs, and treatment duration was 14, 3, and 3 months, respectively. As the fifth line, sunitinib was administered, with significant shrinkage of the multiple liver metastases, and PR has been maintained for 34 months. Conclusion: Sunitinib after an IO-drug showed a significant effect in spite of only slight efficacy with other VEGFR-TKIs, which may have occurred through the alteration of the immunological microenvironment

Automated Quantification of Extranuclear ERα Using Phosphor-Integrated Dots for Predicting Endocrine Therapy Resistance in HR⁺/HER2⁻ Breast Cancer

In addition to genomic signaling, Estrogen receptor alpha (ERα) is associated with cell proliferation and survival through extranuclear signaling contributing to endocrine therapy (ET) resistance. However, the relationship between extranuclear ERα and ET resistance has not been extensively studied. We sought to measure extranuclear ERα expression by immunohistochemistry using phosphor-integrated dots (IHC-PIDs) and to assess its predictive value for ET resistance. After quantitative detection of ERα by IHC-PIDs in vitro, we developed “the nearest-neighbor method„ to calculate the extranuclear ERα. Furthermore, tissue sections from 65 patients with HR+/HER2- BC were examined by IHC-PIDs, and the total ERα, nuclear ERα, extranuclear ERα PIDs score, and ratio of extranuclear-to-nuclear ERα (ENR) were measured using the novel method. We demonstrate that quantification of ERα using IHC-PIDs exhibited strong correlations to real-time qRT-PCR (r2 = 0.94) and flow cytometry (r2 = 0.98). High ERα ENR was significantly associated with poor overall survival (p = 0.048) and disease-free survival (DFS) (p = 0.007). Multivariate analysis revealed that the ERα ENR was an independent prognostic factor for DFS [hazard ratio, 3.8; 95% CI, 1.4–11.8; p = 0.006]. Our automated measurement has high accuracy to localize and assess extranuclear ERα. A high ERα ENR in HR+/HER2− BC indicates decreased likelihood of benefiting from ET