Aggressive early surgical strategy in patients with intracranial hemorrhage: a new cardiopulmonary bypass option.

OBJECTIVE: We present a novel strategy in cardiac surgery with a cardiopulmonary bypass with low-dose heparin and Nafamostat mesylate as an anticoagulant (NM-CPB), which reduces postoperative neurological complications. METHOD AND RESULTS: 19 patients with a mean age of 63.6 ± 20.2 years (range 24-91) and an indication of early cardiac surgery with intracranial complication (ICC) underwent surgery with NM-CPB. The preoperative diagnoses included seven cases of infective endocarditis and six of left atrial appendage thrombosis. ICC were noticed in seven cases with hemorrhages (hemorrhagic infarction: n = 4, subarachnoid hemorrhage: n = 3) and 12 without hemorrhage (large infarction: n = 10, small-multiple infarction at the risk for hemorrhagic transformation: n = 2). The mean interval between a diagnosis and cardiac surgery was 1.1 ± 1.5 days in the ICH cases and 1.4 ± 1.4 days otherwise. In-hospital mortality was 5.3%. The mean CPB time was 146.7 ± 66.03 min, the mean dose of NM, heparin were 2.23 ± 1.59 mg/kg/hr and 56.8 ± 20.3 IU/kg, respectively. The mean activated clotting time (ACT) was 426.8 ± 112.4 s. No further intracranial bleeding and no new hemorrhages were observed after surgery. CONCLUSIONS: In early cardiac surgery with ICC, especially with hemorrhage, NM-CPB reduced postoperative neurological complications. We plan to use NM-CPB to expand the indications and to establish an early aggressive treatment.

The Superiority of AN69ST Membrane in the Adsorption of Fibroblast Growth Factor-23.

BACKGROUND: The most frequent cause of acute kidney injury (AKI) needing renal replacement therapy is sepsis, with the prognosis of patients with septic AKI worse than for other causes of this disease. Recent studies have shown that fibroblast growth factor-23 (FGF-23) levels, one of the phosphaturic and prognostic factors in chronic kidney disease, are also elevated in patients with AKI and correlate with an increased risk of death or a need for dialysis. In addition, FGF-23 was found to inhibit the extra-renal synthesis of 1,25-dihydroxyvitamin D by human monocytes. Therefore, the elevated expression of FGF-23 may play a crucial role in defining the immune response to vitamin D and this, in turn, may be a key determinant of infection in patients. Continuous renal replacement therapy (CRRT) is often essential for the treatment of septic AKI. However, reports related to the influence of CRRT on serum FGF-23 levels are lacking. In this study, we undertook preliminary in vitro investigations evaluating the effect of different types of CRRT membranes on FGF-23 adsorption. METHODS: To study how FGF-23 is adsorbed by hemofiltration fiber, in vitro experiments were performed based on a batch method using three types of fiber: polysulfone (PS), polymethyl methacrylate (PMMA), and acrylonitrileco-methallyl sulfonate surface treatment (AN69ST) fiber. RESULTS: The adsorptive properties of the various membranes were determined from measuring changes in the concentration of FGF-23 in a solution containing the membrane after incubation for 60 or 240 minutes. The amount of FGF-23 adsorbed by an AN69ST membrane was significantly more than for other membranes (P < 0.01). The amounts adsorbed by PS and PMMA membranes were similar. CONCLUSIONS: We found an AN69ST membrane has a greater capacity for FGF-23 adsorption than two other membranes tested. Although this is an in vitro study, we believe the present findings indicate an exciting new direction in the treatment of septic AKI and highlight the necessity of acute clinical investigations using AN69ST-CRRT.

Continuous Hemodiafiltration with an AN69ST Hemofilter (AN69ST-CHDF) as FGF-23-Lowering Therapy.

BACKGROUND: Recent studies have shown that fibroblast growth factor-23 (FGF-23) is elevated not only in chronic kidney disease (CKD), but also in acute illnesses such as acute kidney injury, septic shock, and acute heart failure. FGF-23 would be not only a simple biomarker but also a direct toxic factor in acute illness. Therefore, lowering circulating FGF-23 levels in clinical practice would be an exciting and valuable interventional strategy. Continuous hemodiafiltration (CHDF) is often performed for the treatment of the aforementioned acute illnesses. We have previously reported that an acrylonitrile-co-methallyl sulfonate surface-treated (AN69ST) membrane has a greater capacity for in vitro FGF-23 adsorption than polysulfone and polymethyl methacrylate membranes. However, reports related to the influence of AN69ST-CHDF on serum FGF-23 levels in acute illness are lacking. In this study, we investigated the effect of AN69ST-CHDF on circulating FGF-23 concentrations in clinical practice. METHODS: Subjects comprised six inpatients who underwent AN69ST-CHDF for an acute illness. Blood samples for the measurement of serum FGF-23 were collected at 0, 3, and 12 hours post-treatment. Blood samples were also drawn from the extracorporeal circuit at the inlet and outlet of the hemofilter 3 hours after CHDF initiation, in order to calculate the clearance of serum FGF-23. RESULTS: Three and 12 hours after the start of AN69ST-CHDF, circulating FGF-23 levels decreased from baseline values with a marginal statistical significance (p = 0.0625 and 0.0938, respectively). An FGF-23 clearance of 27.5 [interquartile range: 19.4 - 29.2] mL/minute 3 hours after the initiation of AN69ST-CHDF was achieved. CONCLUSIONS: Our results suggest that AN69ST-CHDF can be a novel FGF-23 lowering therapy for acute illnesses requiring acute blood purification.