PCSK9 and inflammatory biomarkers in the early post kidney transplantation period.

OBJECTIVE:   Various biomarkers have been studied in the early post-kidney transplantation (post-KTx) period in order to identify potential therapeutic targets for improving long-term graft survival. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a biomarker that has recently gained interest in cardiovascular disease but its role still remains to be defined post-KTx. PATIENTS AND METHODS: We prospectively evaluated the levels of PCSK9, interleukin (IL)-6, WBC and C-reactive protein in seventy-three hemodialysis patients undergoing KTx, at 3 time-points; pre-transplantation (day 0) and at 1 and 6-months post-KTx. All data were also analyzed according to donor-type (living or deceased) and compared with hemodialysis patients on transplant waiting list. RESULTS: At Day 0 there was no difference in WBC, CRP, IL-6 and PCSK9 levels between patients scheduled for transplantation and those who remained on hemodialysis. In transplanted patients WBC, CRP and IL-6 levels were significantly reduced early post-KTx [logIL-6 Day 0: 0.68 (0.33, 0.85) vs. 1-month: 0.57 (0.37, 0.75) vs. 6-months: 0.50 (0.32, 0.69) pg/ml, p=0.01], while PCSK9 levels were significantly increased (Day 0: 199.8±63.0 vs. 1-month: 276.2±79.4 vs. 6-months: 245.9±62.5 ng/ml, p<0.001). In contrast, no change of WBC, CRP, IL-6 and PCSK9 levels was observed in hemodialysis patients on follow-up (p=NS for all). Between living-donor and deceased-donor recipients, analysis showed reduced CRP and increased PCSK9 levels in both groups (p<0.05 for all), while IL-6 levels were reduced in living-donor and increased in deceased-donor recipients 1-month post-KTx. PCSK9 levels were not correlated with renal function, delayed graft function, rejection episodes or inflammatory biomarkers. CONCLUSIONS: PCSK9 levels were increased post-KTx independently from renal function and inflammatory biomarkers, in both living and deceased-donor recipients.

The role of amiodarone in recent-onset atrial fibrillation after ibutilide has failed to restore sinus rhythm.

BACKGROUND: Ibutilide is a class III antiarrhythmic drug that is used for the cardioversion of atrial arrhythmias, but it can cause torsades de pointes. Amiodarone is also used for the cardioversion of atrial fibrillation and prolongs the QT interval but rarely causes torsades de pointes. METHODS AND RESULTS: The study included 51 consecutive patients with recent onset atrial fibrillation in whom the administration of ibutilide failed to restore sinus rhythm. In those patients we decided to proceed to intravenous administration of amiodarone. The QT intervals were measured on 12-lead ECG. After 11 +/- 5 h of the administration of the amiodarone, 42 patients (82%) were on sinus rhythm. There was no episode of non-sustained torsades de pointes or hypotension that followed the administration of the two antiarrhythmic agents. CONCLUSIONS: The administration of amiodarone in the case of ibutilide failure may be a useful adjunct to current cardioversion protocols for recent onset atrial fibrillation.

Adjuvant chemotherapy with cisplatin, etoposide, fluorouracil and leucovorin for gastric carcinoma.

PURPOSE: The aim of this study was to evaluate the efficacy of cisplatin, etoposide, 5-fluorouracil (5-FU), and leucovorin (L; CEFL) combination chemotherapy given as adjuvant treatment to patients with stage III gastric cancer. PATIENTS AND METHODS: A total of 33 patients who had undergone curative resection for stage III gastric adenocarcinoma were enrolled in our adjuvant chemotherapy protocol to receive 6 cycles of CEFL starting within 8 weeks from surgery. CEFL consisted of cisplatin 30 mg/m2 on days 1-3; 5-FU 300 mg/m2 continuous infusion on days 1-3; and etoposide 90 mg/m2 on days 1-3. Cycles were repeated every 4 weeks. Relapse-free survival (RFS) and overall survival (OS) were estimated using Kaplan-Meier method. Comparison between groups was carried out using log-rank test. RESULTS: Treatment was completed by 30 (91%) patients. After a mean follow-up of 31 months 15 (50%) patients have relapsed. Mean RFS was 31 months (range 6 to 114+). Patients with stage IIIA disease had longer RFS that those with stage IIIB (37 vs. 25 months, p>0.05). Mean OS was 35 months (range 4 to 114+), while stage IIIA patients survived longer than IIIB ones (42 vs. 27 months, p>0.05). Principal side effects of therapy were from the bone marrow and the gastrointestinal tract. There were 2 treatment-related deaths due to neutropenic sepsis. CONCLUSION: CEFL regimen appears to be an effective adjuvant treatment for patients with stage III gastric carcinoma as it prolongs both RFS and OS. However, its pronounced myelotoxicity requires the prophylactic use of granulocyte colony stimulating factor (G-CSF).