Use of argatroban: experiences in continuous renal replacement therapy in critically ill patients after cardiac surgery.

OBJECTIVES: Acute kidney injury requiring renal replacement therapy (RRT) is a common complication after cardiac surgery, complicated by suspected or proven heparin-induced thrombocytopenia (type II). The present study evaluated the use of argatroban as an anticoagulant during continuous RRT in the early period after cardiac surgery. Argatroban was compared with unfractionated heparin (UH) with respect to bleeding complications and the effectiveness of anticoagulation. METHODS: Patients requiring RRT after cardiac surgery from March 2007 to June 2009 were identified. The effectiveness of anticoagulation was measured indirectly by the duration of dialysis filter use. Bleeding was defined as clinical signs of blood loss or the need for transfusion. RESULTS: Of 94 patients, 41 received argatroban, 27 UH, and 26 required conversion from UH to argatroban. In all 3 subgroups, RRT was begun within a median postoperative period of 2.0 days. Similar levels of anticoagulation were achieved with the duration of the circuit and filter changed an average of 1.1 times daily during RRT. Liver function was comparable in all patients. Neither clinically relevant signs of bleeding nor significant differences in the hemoglobin levels or a requirement for transfusion were noted. However, the Simplified Acute Physiology Score II values during dialysis and mortality were significantly greater in the patients initially receiving argatroban compared with those who received UH alone (54 ± 2 vs 43 ± 3, P < .001; 71% vs 44%, P = .04). CONCLUSIONS: Argatroban can provide effective anticoagulation in postoperative cardiac patients receiving continuous RRT. Close monitoring and dose titration resulted in a comparable risk of bleeding for anticoagulation with both argatroban and heparin, regardless of the disease severity or impaired hepatic function.

Granular cell tumor of the trachea in a child.

Granular cell tumors are uncommon benign neoplasms. Their location is mostly in the head and neck region; appearance in other parts of the body is rare, but it has been reported. We present the case of a 14-year-old girl with a granular cell tumor of the trachea. The tumor was incidentally found at bronchoscopy performed to exclude suspected foreign body aspiration. It was located in the ventral part of the main carina. Biopsies revealed the histologic pattern of a benign granular cell tumor. The girl underwent resection of the main carina followed by reconstruction of a neo-carina with both main bronchi. She has not had any recurrence of the tumor during 3 years of follow-up.

Identification of novel Nox4 splice variants with impact on ROS levels in A549 cells.

NAD(P)H oxidases (Nox) generate reactive oxygen species (ROS) that function in host defense and cellular signaling. While analyzing the expression of Nox4 at the protein and the mRNA levels, we identified four novel Nox4 splice-variants Nox4B, Nox4C, Nox4D, and Nox4E, which are expressed in human lung A549 cell line and lung tissues. One Nox4 isoform lacks the first NAD(P)H binding site (Nox4B) while another lacks all FADH and NAD(P)H binding sites (Nox4C). Cells over-expressing NoxB or Nox4C exhibited a decrease in ROS levels. Thus, these isoforms have dominant negative characteristics for ROS generation. Two other splice-variants (Nox4D, Nox4E) lack the transmembrane domains, suggesting these as non-membrane associated isoforms. Nox4D contains all FADH and NAD(P)H binding domains and shows the same rate of ROS generation as Nox4 prototype. Taken together, we suggest that Nox4 exists as several isoforms that may have different functions in ROS-related cell signaling.