BackgroundAlthough mortality after cardiac surgery has significantly decreased in the last decade, patients still experience clinically relevant postoperative complications. Among others, atrial fibrillation (AF) is a common consequence of cardiac surgery, which is associated with prolonged hospitalization and increased mortality.MethodsWe retrospectively analyzed data from patients who underwent coronary artery bypass grafting, valve surgery or a combination of both at the University Hospital Muenster between April 2014 and July 2015. We evaluated the incidence of new onset and intermittent/permanent AF (patients with pre- and postoperative AF). Furthermore, we investigated the impact of postoperative AF on clinical outcomes and evaluated potential risk factors.ResultsIn total, 999 patients were included in the analysis. New onset AF occurred in 24.9% of the patients and the incidence of intermittent/permanent AF was 59.5%. Both types of postoperative AF were associated with prolonged ICU length of stay (median increase approx. 2 days) and duration of mechanical ventilation (median increase 1 h). Additionally, new onset AF patients had a higher rate of dialysis and hospital mortality and more positive fluid balance on the day of surgery and postoperative days 1 and 2. In a multiple logistic regression model, advanced age (odds ratio (OR) = 1.448 per decade increase, p < 0.0001), a combination of CABG and valve surgery (OR = 1.711, p = 0.047), higher C-reactive protein (OR = 1.06 per unit increase, p < 0.0001) and creatinine plasma concentration (OR = 1.287 per unit increase, p = 0.032) significantly predicted new onset AF. Higher Horowitz index values were associated with a reduced risk (OR = 0.996 per unit increase, p = 0.012). In a separate model, higher plasma creatinine concentration (OR = 2.125 per unit increase, p = 0.022) was a significant risk factor for intermittent/permanent AF whereas higher plasma phosphate concentration (OR = 0.522 per unit increase, p = 0.003) indicated reduced occurrence of this arrhythmia.ConclusionsNew onset and intermittent/permanent AF are associated with adverse clinical outcomes of elective cardiac surgery patients. Different risk factors implicated in postoperative AF suggest different mechanisms might be involved in its pathogenesis. Customized clinical management protocols seem to be warranted for a higher success rate of prevention and treatment of postoperative AF.Electronic supplementary materialThe online version of this article (10.1186/s12871-017-0455-7) contains supplementary material, which is available to authorized users.
Background: Standard-of-care anti-cancer drugs exhibit anti-tumor activity but typically display dose-limiting toxicities in patients. The aim of the current studies was to investigate, whether a combined approach consisting of a pre-treatment with the hydroxyethyl starch solution Voluven® 10% and a subsequent treatment with suboptimal doses of selected anti-cancer drugs improves the anti-cancer efficacy in human tumor xenograft models in mice. Materials and methods: Female NMRI nu/nu mice bearing subcutaneous xenografts of the human lung squamous cell carcinoma LXFE 397 were treated i.v. with 20 ml/kg Voluven® 10% followed by a p.o. treatment with 100 mg/kg capecitabine 1 hour later on days 0, 4, 7, 11, and 14. In a separate study, female NMRI nu/nu mice bearing subcutaneous xenografts of the human head-and-neck carcinoma HNXF 1842 were treated i.v. with 20 ml/kg Voluven® 10% followed by an i.v. treatment with 10 mg/kg paclitaxel 1 hour later on days 0, 7 and 14. In both studies, dosing started on the day of randomization (day 0) when animals carried tumors of appropriate size (50-250 mm3). Saline (20 ml/kg) served as negative control and the anti-cancer drug alone as reference. From the day of first dosing, the tumor growth and body weight were monitored over a time period of 14 days in the lung carcinoma study and 18 days in the head-and-neck carcinoma study. Results: In mice bearing human lung squamous cell carcinoma xenografts, the median relative tumor volume increased approximately 19-fold in the saline group during the 14 days observation time, whereas the reference drug capecitabine moderately inhibited the tumor growth. Combining capecitabine treatment with a Voluven® 10% pre-treatment caused a much stronger inhibitory effect on tumor growth as evidenced by an 8.5-fold median relative tumor volume increase in contrast to a 15.2-fold increase in the reference group (capecitabine). In mice bearing human head-and-neck carcinoma xenografts, the median relative tumor volume of the saline group increased 12.1-fold during the observation period of 18 days. The treatment with paclitaxel caused a tumor growth reduction resulting in a 7.1-fold increase of the median relative tumor volume. This effect was further enhanced by the pre-treatment with Voluven® 10% which resulted in a 4-fold median relative tumor volume increase over 18 days. The combination of Voluven® 10% with capecitabine or paclitaxel did not increase toxicity as demonstrated by the body weight development. Conclusion: We showed for the first time that the pre-treatment with Voluven® 10% 1 hour prior to the administration of the anti-cancer drugs capecitabine or paclitaxel is useful to improve their efficacy in tumor xenograft models in mice. The enhancement of anti-cancer drug effectiveness might allow reducing the dosage of cytotoxic anti-cancer drugs and therefore minimizing unwanted side effects. Citation Format: Silke Baasner, Corinna Lupp, Stefanie Honndorf, Johannes Hermle, Martin Westphal. Combined administration of Voluven® 10% and anti-cancer drugs increases anti-tumor efficacy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4587. doi:10.1158/1538-7445.AM2014-4587
Hydroxyethyl starch (HES) is used clinically to replace blood loss and stabilize hemodynamics. However, the functional consequences on the kidney have not been fully investigated. Here we determine whether a single application of hydroxyethyl starch, dosed to restore blood pressure (BP) within minutes following a blood loss, affects kidney outcome when assessed one day or one week later.MethodsUnder short‐term anesthesia, Sprague‐Dawley rats were subjected to a 25% blood loss over 6.25 min via the femoral vein. Immediately thereafter, the Volulyte® 6% containing HES 130/0.4 (VOL) or Hextend® 6% containing HES 670/0.7 (HEX) or a balanced crystalloid solution (Isolyte®, ISO) were infused i.v. to restore BP within 4–4.5 minutes. Pilot studies established that this required doubling of the infused volume of ISO (20ml/kg) vs VOL and HEX (each 10ml/kg). Sham operated rats without blood loss/volume substitution were used as control (CON). Renal function was determined in renal clearance studies (using 3H‐inulin and paramino hippurate [PAH]) under terminal anesthesia. In separate groups of animals plasma and urine were collected and kidneys harvested for gene expression analysis. N=10–11/group.ResultsAs expected, hematocrit was significantly lower at 1 day after hemorrhage versus CON. The initial hematocrit drop at day 1 and the subsequent recovery after 1 week were similar in ISO, VOL and HEX. As indicated by similar values for body weight, blood pressure, plasma electrolytes, and hormone markers (including renin, ANP and ADH) among the 4 groups, the 3 volume substitution protocols rapidly restored the volume status at 1 day after hemorrhage and this effect was sustained 1 week later. The data also indicated that ISO, VOL and HEX similarly preserved renal hemodynamics (GFR, RBF), tubular reabsorption (Na, K, Cl, fluid, glucose, calcium, phosphate) and tubular secretion (PAH) at 1 day and 1 week after hemorrhage. Measurement of albuminuria and markers of kidney injury and inflammation (incl. urine NGAL to creatinine ratios and renal mRNA expression of KIM‐1, CCL2 and IL6) indicated that the level of injury or inflammation was not consistently increased among any of the 4 groups.ConclusionA single bolus infusion of ISO, VOL or HEX, dosed to acutely restore BP after a 25% blood loss in rats, preserved or maintained integrated kidney function to a similar extent, when assessed one day or one week later.Support or Funding InformationFresenius Kabi Deutschland GmbHThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
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