Detailed exploration of pathophysiology involving inflammatory status and bleeding symptoms between lipopolysaccharide- and tissue factor-induced disseminated intravascular coagulation in rats.

Lipopolysaccharide (LPS) and tissue factor (TF) have frequently been used to induce disseminated intravascular coagulation (DIC) in experimental animal models. We have previously reported that the pathophysiology of DIC differs according to the inducing agents. However, inflammatory status and bleeding symptoms have not been fully compared between rat models of the two forms of DIC. We attempted to evaluate detailed characteristic features of LPS- and TF-induced DIC models, especially in regard to inflammatory status and bleeding symptoms, in addition to selected hemostatic parameters and pathologic findings in the kidneys. The degree of hemostatic activation in both types of experimental DIC was identical, based on the results of thrombin-antithrombin complex levels. Markedly elevated tumor necrosis factor, interleukin-6, and high-mobility group box-1 concentrations were observed with severe organ dysfunction and marked fibrin deposition in the kidney on administration of LPS, whereas markedly elevated D-dimer concentration and bleeding symptoms were observed with TF administration. Pathophysiology such as fibrinolytic activity, organ dysfunction, inflammation status, and bleeding symptom differed markedly between LPS- and TF-induced DIC models in rats. We, therefore, recommend that these disease models be assessed carefully as distinct entities to determine the implications of their experimental and clinical use.

Sarcopenia may Influence the Prognosis in Advanced Thyroid Cancer Patients Treated With Molecular Targeted Therapy.

BACKGROUND/AIM: Reportedly, sarcopenia and nutritional status are associated with prognosis in cancer patients. However, data regarding the relationship of these factors with advanced thyroid cancer patients receiving molecular targeted therapy remains scarce. Therefore, we investigated the relationship between nutritional assessment, as well as sarcopenia, and prognosis in patients with advanced thyroid cancer undergoing molecular targeted therapy. PATIENTS AND METHODS: In this retrospective study, sarcopenia and several markers of nutritional status were assessed in advanced thyroid cancer patients at the Kanazawa University Hospital, before the introduction of molecular targeted therapy. RESULTS: Advanced thyroid cancer patients with sarcopenia presented a worse prognosis than those without sarcopenia. Additionally, sarcopenia strongly correlated with several markers of nutritional status, such as albumin, prognostic nutrition index, and Glasgow prognostic score. CONCLUSION: Sarcopenia could be a prognostic factor in patients with advanced thyroid cancer receiving molecular targeted therapy.

Risk Factors for Delayed Elimination of Methotrexate in Children, Adolescents and Young Adults With Osteosarcoma.

BACKGROUND/AIM: High-dose methotrexate (HD-MTX) is pivotal chemotherapy in the treatment of patients with osteosarcoma. Blood concentrations of MTX are associated with several side effects, but there are large individual differences in the elimination of MTX. The aim of this study was to explore risk factors for delayed elimination of MTX in children, adolescents and young adults with osteosarcoma. PATIENTS AND METHODS: We conducted a retrospective study on Japanese patients with osteosarcoma who were treated with HD-MTX at Kanazawa University Hospital from April 2006 to March 2015. Risk factors for delayed elimination of methotrexate were identified by multiple logistic regression analysis. RESULTS: A total of 92 cycles of HD-MTX therapy were analyzed. Female and lower creatinine clearance (CCr) were identified as independent risk factors for delayed elimination of MTX. CONCLUSION: Knowing the factors associated with delayed elimination of MTX could lead to safer and optimized chemotherapy for patients with osteosarcoma.

Detailed assessment and risk factor analysis of corticosteroid-induced psychiatric disorders in pediatric, adolescent, and young adult patients undergoing induction or consolidation therapy for hematologic malignancy.

BACKGROUND: Corticosteroid-induced psychiatric disorders (CIPDs) represent an adverse effect that can cause severe emotional and behavioral problems. The aim of the present study was to assess the incidence and risk factors of CIPDs. METHODS: A retrospective analysis of 92 pediatric and young adult patients with hematologic malignancies was conducted. RESULTS: The incidence of CIPDs in patients receiving a treatment regimen with prednisolone or dexamethasone was 64.9% and 77.5%, respectively, both of which were significantly higher than that in patients not receiving corticosteroids. Independent risk factors and adjusted odds ratios (95% confidence intervals) related to severe CIPD were 2.15 (1.11-4.18) for dexamethasone (using prednisolone as the reference) and 0.81 (0.75-0.87) for age, suggesting that the odds increase with decreasing age. Frequently observed symptoms, respectively in terms of behavioral and emotional problems were defiance, crying, psychomotor excitement, dysphoria, irritability, and depression. To our knowledge, this is the first report to mention the risk factors and characteristics for clinical symptoms of CIPDs during the developmental process. CONCLUSIONS: Healthcare professionals should predict and prepare for psychiatric adverse events prior to chemotherapy in the clinical settings, especially in patients in younger age and receiving a treatment regimen with dexamethasone.

Clinical Characteristics Associated With Lenvatinib-induced Fistula and Tumor-related Bleeding in Patients With Thyroid Cancer.

BACKGROUND: Lenvatinib has become an important treatment option for advanced thyroid cancer. Fistula and tumor-related bleeding are life-threatening adverse effects that are triggered by tumor shrinkage. The aim of this study was to evaluate basic parameters, such as time and tumor shrinkage level, and analyze patient characteristics that might be related to onset of complications. PATIENTS AND METHODS: A retrospective study of 16 patients who received lenvatinib for thyroid cancer treatment was performed. RESULTS: Fistula was observed in two patients (12.5%), while tumor-related bleeding was observed in one (6.3%). Complications were found to appear at 10.4 weeks from initiation and with tumor decrease of 19.2%. Risk factors for complications were identified as anaplastic histological type, tumor invasion, and leukocytopenia induced by lenvatinib. CONCLUSION: Individual dose adjustment is needed with respect to these features in order to manage severe adverse effects induced by lenvatinib.