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Phase I trial of alpha-particle immunotherapy with 225Ac-lintuzumab and low-dose cytarabine in patients age 60 or older with untreated acute myeloid leukemia.

456Objectives: 225Ac-lintuzumab is a radioimmunoconjugate composed of 225Ac, which emits 4 α-particles, linked to a humanized anti-CD33 monoclonal antibody. An initial phase I trial showed that a single infusion of 225Ac-lintuzumab is safe at doses ≤ 111 kBq/kg and has activity in relapsed/refractory acute myeloid leukemia (AML). We conducted a multicenter, phase I dose-escalation trial to determine the maximum tolerated dose (MTD), toxicity, and biological activity of fractionated-dose 225Ac-lintuzumab in combination with low-dose cytarabine (LDAC).Methods: Patients 蠅 60 years with untreated AML not candidates for intensive chemotherapy were eligible. Patients received LDAC 20 mg twice daily for 10 days every 4-6 weeks for up to 12 cycles. During Cycle 1, 2 fractions of 225Ac-lintuzumab were given 1 week apart, beginning 4-7 days following completion of LDAC. To prevent radiation-induced nephrotoxicity, patients were given furosemide while receiving 225Ac-lintuzumab then spironolactone for 1 year afterward. Four dose levels of 225Ac-lintuzumab were studied using a 3+3 design.Results: Eighteen patients (median age, 77 years; range, 68-87) completed therapy. Twelve (67%) had prior myelodysplastic syndrome (MDS), for which 10 (83%) received therapy with hypomethylating agents (n=9) or allogeneic hematopoietic cell transplantation (n=1). Eleven patients (61%) had intermediate-risk and 7 (39%) had poor-risk AML. Median CD33 expression was 81% (range, 30-100%). 225Ac...
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Radiopharmaceutical Therapy- Radioimmunotherapy and Radioembolization Source Type: research

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CONCLUSION: Although overall results are comparable to other regions worldwide, pre-LT treatment not only considering imaging data but also AFP values should be contemplated during the next years. PMID: 29469048 [PubMed - in process]
Source: Annals of Hepatology - Category: Gastroenterology Tags: Ann Hepatol Source Type: research
DISCUSSION: The addition of PTX to AMO in the treatment of HRS-1 is safe when compared to the current standard of care. Future large-scale prospective study to validate the efficacy of this treatment seems warranted. PMID: 29469046 [PubMed - in process]
Source: Annals of Hepatology - Category: Gastroenterology Tags: Ann Hepatol Source Type: research
CONCLUSION: Adiponectin but not resistin levels were associated with intensity of liver dysfunction and worse prognosis in patients with alcoholic liver disease, suggesting a potential as a prognostic biomarker. PMID: 29469045 [PubMed - in process]
Source: Annals of Hepatology - Category: Gastroenterology Tags: Ann Hepatol Source Type: research
We describe the technique and interpretation of commercially available VET and assess the application of VET in both transplant and non-transplant cirrhosis populations. VET largely correlates well with traditional testing including platelet count and fibrinogen level, however, is potentially less accurate in patients with low fibrinogen levels. VET may be useful in identifying patients at higher risk of hypercoagulable complications post-transplant and reflects changes in hemostasis in decompensated patients. While VET has been associated with decreased transfusión support in multiple studies, the lack of bleeding ...
Source: Annals of Hepatology - Category: Gastroenterology Tags: Ann Hepatol Source Type: research
No abstract available
Source: RETINA - Category: Opthalmology Tags: New Instruments Source Type: research
Source: BMJ Comments - Category: General Medicine Source Type: forums
Conclusions: Owing to increasing incidence and declining mortality, the number of sepsis survivors at risk for hospital readmission rose significantly between 2010 and 2015. The 30-day hospital readmission rates for sepsis declined modestly but were offset by a rise in emergency department treat-and-release visits.
Source: Critical Care Medicine - Category: Emergency Medicine Tags: Late Breaker Articles Source Type: research
Conclusions: Impaired fibrinolysis, mainly driven by plasminogen activator inhibitor-1 increase and thrombin activatable fibrinolysis inhibitor activation, is an early manifestation of sepsis and may precede the development of thrombocytopenia. Thrombin activatable fibrinolysis inhibitor level, in particular, proved to be an independent predictor of mortality, which may improve risk stratification of patients with severe sepsis.
Source: Critical Care Medicine - Category: Emergency Medicine Tags: Online Clinical Investigations Source Type: research
Objectives: To assess whether serum concentration of endothelial cell-specific molecule-1 (Endocan) at ICU admission is associated with the use of ICU resources and outcomes in critically ill hematology patients. Design: Prospective multicenter cohort study. Setting: Seventeen ICUs in France and Belgium. Patients: Seven hundred forty-four consecutive critically ill hematology patients; 72 critically ill septic patients without hematologic malignancy; 276 healthy subjects. Intervention: None. Measurements and Main Results: Median total endocan concentrations were 4.46 (2.7–7.8) ng/mL. Endocan concentr...
Source: Critical Care Medicine - Category: Emergency Medicine Tags: Online Clinical Investigations Source Type: research
Conclusions: Our data suggest that targeting the sphingosine kinase 1–/sphingosine-1-phosphate–/sphingosine-1-phosphate receptor 2–signaling pathway in the lung may provide a novel therapeutic perspective in pneumococcal pneumonia for prevention of acute lung injury.
Source: Critical Care Medicine - Category: Emergency Medicine Tags: Online Laboratory Investigation Source Type: research
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