A novel device for reducing hemolysis provoked by cardiotomy suction during open heart cardiopulmonary bypass surgery: a randomized prospective study

Since the inception of cardiopulmonary bypass (CPB), little progress has been made concerning the design of cardiotomy suction (CS). Because this is a major source of hemolysis, we decided to test a novel device (Smartsuction [SS]) specifically aimed at minimizing hemolysis during CPB in a clinical setting. Block randomization was carried out on a treated group (SS, n=28) and a control group (CTRL, n=26). Biochemical parameters were taken pre-, peri-, and post CPB and were compared between the two groups using the Student's t-test with statistical significance when P<0.05. No significant differences in patient demographics were observed between the two groups. Lactate dehydrogenase (LDH) and plasma free hemoglobin (PFH) pre-CPB were comparable for the CTRL and SS groups, respectively. LDH peri-CPB was 275+/-100 U/L versus 207+/-83 U/L for the CTRL and SS groups, respectively (P<0.05). PFH was 486+/-204 mg/L versus 351+/-176 mg/L for the CTRL and SS groups, respectively (P<0.05). LDH post CPB was 354+/-116 U/L versus 275+/-89 U/L for the CTRL and SS groups, respectively (P<0.05). PFH was 549+/-271 mg/L versus 460+/-254 mg/L for the CTRL and SS groups, respectively (P<0.05). Preoperative hematocrit (Hct) of 43+/-5% (CTRL) versus 37+/-5% (SS), and hemoglobin (Hb) of 141+/-16 g/L (CTRL) versus 122+/-17 g/L (SS) were significantly lower in the SS group. However, when normalized (N), the SS was capable of conserving Hct, Hb, and erythrocyte count perioperatively. Erythrocytes (N) were 59+/-5% (CTRL) versus 67+/-9% (SS); Hct (N) was 59+/-6% (CTRL) versus 68+/-9% (SS), and Hb (N) was 61+/-6% (CTRL) versus 70+/-10% (SS) (all P<0.05). This novel SS device evokes significantly lowered blood PFH and LDH values peri- and post CPB compared with the CTRL blood using a CS system. The SS may be a valuable alternative compared to traditional CS techniques.     

Incidence,Risk Factors,and Outcomes of Hyperbilirubinemia in Adult Cardiac Patients Supported by Veno‐Arterial ECMO

The aims of this study were to evaluate the incidence, risk factors, and outcomes of hyperbilirubinemia in cardiac patients with veno‐arterial (VA) ECMO. Data on 89 adult patients with cardiac diseases who received VA ECMO implantation in our hospital were retrospectively reviewed. All patients were divided into the following three groups: 24 in normal group (N, total bilirubin [TBIL] ≤3 mg/dL), 30 in high bilirubin group (HB, 6 mg/dL ≥ TBIL > 3 mg/dL), and 35 in severe high bilirubin group (SHB, TBIL > 6 mg/dL). lg(variables + 1) was performed for nonnormally distributed variables. The incidence of hyperbilirubinemia (>3 mg/dL) was 73%. In a multiple linear regression analysis, lg(peak TBIL + 1) was significantly associated with lg(peak AST + 1) (b‐coefficient 0.188, P = 0.001), lg(peak pFHb + 1) (b‐coefficient 0.201, P = 0.003), and basic TBIL (b‐coefficient 0.006, P = 0.009). Repeated measurement analysis of variance revealed that the main effect for three groups in pFHb and lg(AST + 1) was significant at first 3 days during ECMO. The patients in SHB had low platelets during ECMO and low in‐hospital survival rate. Hyperbilirubinemia remains common in patients with VA ECMO and is associated with low platelets and high in‐hospital mortality. Hemolysis and liver dysfunction during ECMO and basic high bilirubin levels are risk factors of hyperbilirubinemia.     

The impact of roller pump‐assisted cardiotomy suction unit on hemolysis

Hemolysis in cardiac surgery is often related to the contact of blood with air or artificial surfaces. Variations of negative pressure in the suction cannulas may represent an additional factor. Limited data exist on the contribution of a roller pump‐assisted (RPA) cardiotomy suction unit to hemolysis. Elevation of free hemoglobin (fHb) following air suction (AS) or suction tip occlusion (STO) events of a pump‐assisted cardiotomy suction unit was investigated in a mock circuit filled with blood from slaughtered domestic pigs. AS‐associated hemolysis was measured over 240 minutes with 2 minutes of AS occurring every 10 minutes. STO‐associated hemolysis was analyzed over 80‐minute periods: configuration 1 (c1) comprised a cycle of 20 minutes (min) occlusion and 60 minutes RPA flow (20/60 minutes); c2 comprised 20 cycles of 1/3 minutes; c3 comprised 40 cycles of 0.5/1.5 minutes; and c4 comprised 80 cycles of 0.25/0.75 minutes. The AS setup did not lead to significant hemolysis after 2 (P = .97), 3 (P = .40) or 4 (P = .11) hours. The STO setup showed the greatest hemolysis (ΔfHb of 30 mg/dL) in c1 after 20 minutes. ΔfHb was different in c1 from all other configurations at 20 minutes (P < .0001) and 80 minutes (P < .05). Ex vivo generation of large negative pressures by STO events is the main cause of cardiotomy suction‐associated hemolysis. The clinical relevance of this mechanism needs further investigations.     

A J‐Shaped Association Between Serum Uric Acid Level and Allograft Outcomes After Living Donor Kidney Transplantation

Hyperuricemia following kidney transplantation (KT) may contribute to a decline in allograft renal function, but be affected by KT‐related confounding factors. Some studies have even suggested that a reduction in serum uric acid (UA) is associated with poor patient outcomes. Thus, we retrospectively analyzed the impact of serum UA on allograft outcomes in 281 KT recipients. KT recipients were divided into five groups according to serum UA level (mg/dL): Group I (n = 46), ≤ 5; Group II (n = 62), >5 and ≤6; Group III (n = 70), >6 and ≤7; Group IV (n = 53), >7 and ≤8; Group V (n = 50), >8. Regression analysis showed that serum UA level was significantly associated with future allograft function. In a Kaplan–Meier analysis, the dialysis‐free survival of Group II recipients was better than that of the other groups (Group I, 140 ± 5 months; Group II, 208 ± 7 months; Group III, 148 ± 4 months; Group IV, 185 ± 12 months; Group V, 164 ± 11 months; P = 0.0164). In Cox proportional hazard models adjusting for estimated glomerular filtration rate, the relative risk of allograft loss still tended to be elevated in Group I (HR=3.417, 95% CI 1.138–10.258) and Group V (HR=2.793, 95% CI 1.108–7.041), using Group II as the reference. Our results suggest that there is a J‐shaped association between serum UA levels and allograft outcomes in living donor KT recipients.     

The effects of magnesium and vitamin E co‐supplementation on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized,double‐blind,placebo‐controlled trial

This study was carried out to determine the effects of magnesium and vitamin E co‐supplementation on wound healing and metabolic status in patients with diabetic foot ulcer (DFU). The current randomized, double‐blind, placebo‐controlled trial was conducted among 57 patients with grade 3 DFU. Participants were randomly divided into two groups to take either 250 mg magnesium oxide plus 400 IU vitamin E (n = 29) or placebo per day (n = 28) for 12 weeks. Compared with the placebo, taking magnesium plus vitamin E supplements reduced ulcer length (β [difference in the mean of outcomes measures between treatment groups] ?0.56 cm; 95% CI, ?0.92, ?0.20; p = 0.003), width (β ?0.35 cm; 95% CI, ?0.64, ?0.05; p = 0.02) and depth (β ?0.18 cm; 95% CI, ?0.33, ?0.02; p = 0.02). In addition, co‐supplementation led to a significant reduction in fasting plasma glucose (β ?13.41 mg/dL; 95% CI, ?20.96, ?5.86; p = 0.001), insulin (β ?1.45 μIU/ml; 95% CI, ?2.37, ?0.52; p = 0.003), insulin resistance (β ?0.60; 95% CI, ?0.99, ?0.20; p = 0.003) and HbA1c (β ?0.32%; 95% CI, ?0.48, ?0.16; p < 0.003), and a significant elevation in insulin sensitivity (β 0.007; 95% CI, 0.003, 0.01; p < 0.001) compared with the placebo. Additionally, compared with the placebo, taking magnesium plus vitamin E supplements decreased triglycerides (β ?10.08 mg/dL; 95% CI, ?19.70, ?0.46; p = 0.04), LDL‐cholesterol (β ?5.88 mg/dL; 95% CI, ?11.42, ?0.34; p = 0.03), high sensitivity C‐reactive protein (hs‐CRP) (β ?3.42 mg/L; 95% CI, ?4.44, ?2.41; p < 0.001) and malondialdehyde (MDA) (β ?0.30 μmol/L; 95% CI, ?0.45, ?0.15; p < 0.001), and increased HDL‐cholesterol (β 2.62 mg/dL; 95% CI, 0.60, 4.63; p = 0.01) and total antioxidant capacity (TAC) levels (β 53.61 mmol/L; 95% CI, 4.65, 102.57; p = 0.03). Overall, magnesium and vitamin E co‐supplementation for 12 weeks to patients with DFU had beneficial effects on ulcer size, glycemic control, triglycerides, LDL‐ and HDL‐cholesterol, hs‐CRP, TAC, and MDA levels.     

Selecting an optimal cutoff value for creatinine in the model for end‐stage liver disease equation

Huo T‐I, Hsu C‐Y, Lin H‐C, Lee P‐C, Lee J‐Y, Lee F‐Y, Hou M‐C, Lee S‐D. Selecting an optimal cutoff value for creatinine in the model for end‐stage liver disease equation.
Clin Transplant 2009 DOI: 10.1111/j.1399‐0012.2009.01099.x.
© 2009 John Wiley & Sons A/S. Abstract: Background: The model for end‐stage liver disease (MELD) is used for organ allocation in liver transplantation. The maximal serum creatinine (Cr) level for MELD is set at 4.0 mg/dL; however, there was no outcome data to justify this strategy. Methods: Ninety‐two patients with cirrhosis with Cr level >4 mg/dL were selected from 1438 patients and compared with MELD score‐matched controls for three‐month and six‐month mortality. Results: At three months, patients with Cr level >4 mg/dL had a significantly higher mortality rate than the 184 controls with a lower Cr level (44.6% vs. 29.3%, p = 0.015). This trend was still significant at six months: the mortality rate was 62% in the index group vs. 45.1% in the control group (p = 0.011). The difference between the index and control groups was the smallest (2.5% at three months and 3.4% at six months) when Cr was up‐scaled to 5.5 mg/dL. The predictive accuracy of the MELD was estimated by using area under receiver‐operating characteristic (AUC) curve. Only the cutoff of 5.5 mg/dL at six months displayed a higher AUC (0.753). Conclusions: A cutoff at 5.5 mg/dL may be more appropriate for the MELD. The MELD for patients with cirrhosis with advanced renal insufficiency deserves re‐evaluation.     

Bioabsorbable device for small‐caliber vessel anastomosis

Although the devices for large‐caliber vessel (>2‐mm diameter) anastomosis are available, there are no devices for performing anastomosis of small‐caliber vessels. We designed a hooked device composed of a bioabsorbable polymer for sutureless anastomosis of small‐caliber vessels. The efficacy of this device was evaluated by in vitro degradation and arterial‐fixation strength tests as well as in vivo transplantation experiments with common carotid arteries of growing SD rats. A nonabsorbable device without hooks served as the control in the fixation strength and animal experiments. The tensile strength of the bioabsorbable device decreased to 27 and 9% of the initial value after 8‐ and 24‐week incubation, respectively. The fixation strength was greater and the anastomotic time was shorter with this device than with the control. The transplantation experiments showed complete endothelial bridging in both devices at 2 weeks after surgery (n = 6). The control device created a considerable protrusion into the arterial lumen at 8 postoperative weeks, whereas the experimental device did not (n = 6). Arterial diameter measurements detected a significant difference between the inner diameters at the respective anastomotic sites (n = 6, P < 0.05) and demonstrated that the control device hindered the vessel growth while the experimental device did not. Therefore, the bioabsorbable hooked device was an effective tool for anastomosis of small‐caliber arteries (ca. 1‐mm diameter). © 2010 Wiley‐Liss, Inc. Microsurgery 30:494–501, 2010.     

Interference in the anti‐Xa heparin activity assay due to hemolysis and icterus during pediatric extracorporeal life support

Chromogenic anti‐Xa assays for unfractionated heparin monitoring (heparin activity) are susceptible to interference from hemolysis and icterus. The purpose of this study was to better understand the effect of hemolysis and icterus on anti‐Xa heparin activity and to predict the magnitude of the error. Increasing levels of hemoglobin and unconjugated bilirubin were added to pooled normal plasma or buffer containing known levels of heparin. Increased plasma hemoglobin or bilirubin produced falsely increased residual factor Xa activity as measured by the absorbance change (OD/min) in the Stago heparin activity assay. This increased absorbance change slope resulted in falsely lower estimates of heparin activity. The falsely lower heparin activity measurement occurred even when heparin was not present, indicating it was not due to heparin neutralization. In a sample containing 0.62 ± 0.06 U/mL heparin and 228 mg/dL hemoglobin, the measured heparin activity was 0.41 ± 0.03 U/mL, underestimating heparin activity by 0.21 ± 0.07 U/mL. Interference occurred if plasma hemoglobin was above 70 mg/dL or bilirubin was above 16 mg/dL, which happened in 16%–26% of samples from pediatric patients on extracorporeal life support (ECLS). In conclusion, hemolysis and icterus were common in ECLS patients, leading to underestimates of unfractionated heparin activity and potentially higher doses of heparin than intended. The magnitude of the heparin activity measurement error could be predicted based on plasma hemoglobin and bilirubin levels until these levels exceeded the technical limits of the assay, ~230 mg/dL hemoglobin and 55 mg/dL bilirubin.     

Prognostic Significance of 1‐Year Serum Albumin Levels Within the Normal Range After Kidney Transplantation

Hypoalbuminemia is associated with poor outcomes in kidney transplantation (KT). However, what level is optimal in serum albumin is not clear for the long‐term prognosis. To determine whether the long‐term outcomes are different even between the normal ranges of serum albumin after KT, we analyzed data from 404 renal allograft recipients whose 1‐year post‐transplant serum albumin levels were within the normal limits (3.5–5.5 g/dL). During a follow‐up of 122 ± 56 months, 97 graft losses, 20 patient deaths, and 50 cardiovascular (CV) events occurred. Based on 1‐year serum albumin levels, the patients were divided into high normal (≥4.6 g/dL, n = 209) and low normal (<4.6 g/dL, n = 195) groups. Kaplan–Meier analyses revealed that the low normal group had poorer allograft survival (P = 0.01), patient survival (P < 0.001), and CV event‐free survival (P < 0.001) than the high normal group. Cox regression analysis confirmed that 1‐year serum albumin was inversely associated with the risk of graft loss (hazard ratio [HR] 0.414, 95% confidence interval [CI] 0.200–0.856), patient death (HR 0.097, 95% CI 0.019–0.484), and CV events (HR 0.228, 95% CI 0.074–0.702). In conclusion, a relatively low 1‐year post‐transplant serum albumin level within the normal limits (<4.6 g/dL) significantly predicts poor long‐term outcomes.     

Comparison of the Effects of Three Cell Saver Devices on Erythrocyte Function During Cardiopulmonary Bypass Procedure—A Pilot Study

Cell salvage devices are routinely used to process red blood cells (RBCs) shed during cardiac surgery. The purpose of this study was to evaluate three commercially available cell saver (CS) devices in terms of erythrocyte function and the quality of washed RBCs during cardiopulmonary bypass (CPB). Thirty patients undergoing CPB were randomly allocated to three CS devices: Group C (Cell Saver 5+; Haemonetics, n = 10), Group M (autolog; Medtronic, n = 10), and Group F (CATS; Fresenius HemoCare, n = 10). Blood samples were collected from reservoirs and transfusion bags. Reservoirs and washed RBCs were analyzed for erythrocyte aggregation index, deformation index (DI) and hematocrit viscosity, 2,3‐diphosphoglycerate (2,3‐DPG), hematocrit (Hct), hemoglobin (Hb), free Hb removal (ΔfHb), glucose (Glu), lactate (Lac), and blood urea nitrogen. After processing, Groups C (P = 0.026) and M (P = 0.032) had relatively higher erythrocyte DI compared with Group F. Group C had lower Δ2,3‐DPG compared with Groups M (P = 0.001) and F (P = 0.001). Group F provided the maximum concentration of Hct (P = 0.021; 0.046) and Hb (P = 0.008; 0.013). In addition, Groups C (P = 0.035) and M (P = 0.038) had a higher removal of fHb (ΔfHb), differing significantly with Group F. In conclusion, CS devices use the same theory of centrifugation; however, based on different designs, the function of the washed erythrocyte and undesirable content removal efficiency differs widely from one device to another.     

An objective definition for clinical suspicion of T‐cell‐mediated rejection after liver transplantation

A uniform definition of clinical suspicion of T‐cell‐mediated rejection (TCMR) in liver transplantation (LT) is needed to homogenize clinical decisions, especially within randomized trials. This multicenter study included a total of 470 primary LT recipients. The derivation cohort consisted of 142 patients who had clinically driven liver biopsies at any time after LT. The external validation cohort included 328 patients who underwent protocol biopsies at day 7‐10 after LT. The rates of moderate‐severe histological TCMR were 33.8% in the derivation cohort and 43.6% in the validation cohort. Independent predictors (ie, risk factors) of moderate‐severe TCMR in the derivation cohort were as follows: serum bilirubin >4 mg/dL (OR=5.83; P<.001), rising bilirubin within the 4 days prior to liver biopsy (OR=4.57; P=.003), and blood eosinophils count >0.1×10⁹/L (OR=3.81; P=.004). In the validation cohort, the number of risk factors was an independent predictor of moderate‐severe TCMR (OR=1.74; P=.001), after controlling for hepatitis C status. The number of risk factors paralleled the rates of moderate‐severe TCMR in the derivation and validation cohorts (P<.001 in both comparisons). In conclusion, increased serum bilirubin, rising bilirubin and eosinophilia are validated risk factors for moderate‐severe histological TCMR and could be used as objective criteria to select candidates for liver biopsy.     

Temporary Right Ventricular Mechanical Support in High‐Risk Left Ventricular Assist Device Recipients Versus Permanent Biventricular or Total Artificial Heart Support

Early planned institution of temporary right ventricular assist device (RVAD) support with the CentriMag (Levitronix LLC, Waltham, MA, USA) in left ventricular assist device (LVAD) recipients was compared with permanent biventricular assist device (BVAD) or total artificial heart (TAH) support. Between 2007 and 2011, 77 patients (age range: 25–70 years) with preoperative evidence of biventricular dysfunction (University of Pennsylvania score >50; University of Michigan score >5) were included. Forty‐six patients (38 men; median age 54.5 years, range: 25–70 years) underwent LVAD placement combined with temporary RVAD support (group A); in 31 patients (25 men; median age 56.7 years, range: 28–68 years), a permanent BVAD or TAH implantation (group B) was performed. Within 30 days, 12 patients from group A (26.08%) and 14 patients from group B (45.1%) died on mechanical support (P = 0.02). Thirty patients (65.2%) in group A were weaned from temporary RVAD support and three (6.5%) underwent permanent RVAD (HeartWare, Inc., Framingham, MA, USA) placement. A total of 26 patients (56.5%) were discharged home in group A versus 17 (54.8%) in group B (P = 0.56). Three patients (8.5%) received heart transplantation in group A and six (19.3%) in group B (P = 0.04). In group A, 90‐day and 6‐month survival was 54.3% (n = 25) versus 51.6% (n = 16) in group B (P = 0.66). In group A, 1‐year survival was 45.6% (n = 21) versus 45.1% (n = 14) in group B (P = 0.81). The strategy of planned temporary RVAD support in LVAD recipients showed encouraging results if compared with those of a similar permanent BVAD/TAH population. Weaning from and removal of the temporary RVAD support may allow patients to be on LVAD support only despite preoperative biventricular dysfunction.     

D‐dimers Are a Predictor of Clot Volume Inside Membrane Oxygenators During Extracorporeal Membrane Oxygenation

Thrombosis inside the membrane oxygenator (MO) is a critical complication during venovenous extracorporeal membrane oxygenation (ECMO). The aim of this study was to prove if thrombotic clots manifest within the MO when D‐dimer levels are elevated over a long‐term period. Heparin‐coated polymethylpentene MOs (n = 13) were exchanged due to high plasma D‐dimer levels. Clot volume was calculated using multidetector computed tomography (MDCT). Coagulation parameters and MO function were analyzed before and after MO exchange. Before MO exchange, D‐dimer levels increased significantly in each patient (11.5 [6.5–15.5] mg/L to 35.0 [34–35] mg/L, P ≤ 0.001). High levels of D‐dimers were tolerated for 1 to 6 days. Additionally, fibrinogen concentration (n = 8) and platelet count decreased (n = 8). Within 48 h after exchange, D‐dimer levels decreased significantly (n = 11, 12 [8–16] mg/L, P = 0.004). Fibrinogen concentration and platelet counts increased. Clots were found in all MOs in the inlet part of the device. Clot volume (16–106 cm³) did not correlate with MO support time but increased significantly when high D‐dimer levels were accepted for >2 days. An increase or high levels of D‐dimers in absence of other explaining pathology during ECMO therapy reflected coagulation activity within the MO. Evidence of clots within the MO at high D‐dimer levels and decrease after exchange underline the relevance of D‐dimer testing during ECMO treatment. Besides, surveillance of MOs during ongoing ECMO therapy will help to predict clot formation, and to avoid system‐induced coagulation disorders as well as critical situations.     

Blood Purification With CytoSorb in Critically Ill Patients: Single‐Center Preliminary Experience

The CytoSorb adsorber, a blood purification therapy, is able to remove molecules in the 5–60 kDa range which comprises the majority of inflammatory mediators and some endogenous molecules. We aimed to evaluate CytoSorb therapy on clinical outcomes in critically ill patients. A retrospective case series study, from February 2016 to May 2017, was performed in 40 patients with multiple organ failure who received CytoSorb treatment. There were 28 patients with cardiogenic shock, 2 with septic shock, 9 with acute respiratory distress syndrome, and 1 with liver failure. Nineteen patients (47%) underwent extracorporeal membrane oxygenation, 11 (27%) had an intra‐aortic balloon pump, 9 (22%) were implanted with Impella, 6 (15%) had a ventricular assist device, and 18 (45%) were treated with continuous veno‐venous hemofiltration. After CytoSorb treatment, total bilirubin decreased from 11.6 ± 9.2 to 6.8 ± 5.1 mg/dL (P = 0.005), lactate from 12.1 ± 8.7 to 2.9 ± 2.5 mmol/L (P < 0.001), CPK from 2416 (670–8615) to 281 (44–2769) U/L (P < 0.001) and LDH from 1230 (860–3157) to 787 (536–1148) U/L (P < 0.001). The vasoactive‐inotropic score after 48 h of treatment was reduced to 10 points, P = 0.009. Thirty‐day mortality was 55% and ICU mortality was 52.5% at expected ICU mortality of 80%. Our study shows that CytoSorb^TM treatment is effective in reducing bilirubin, lactate, CPK and LDH, in critically ill patients mainly due to cardiogenic shock. There is a need for randomized controlled trials to conclude on the potential benefits blood purification with CytoSorb in critically ill patients.     

Conversion to Sirolimus in Renal Transplant Recipients: A Single‐Center Experience

Maintenance immunosuppression with calcineurin inhibitors (CNI) following renal transplantation is associated with nephrotoxicity and accelerated graft loss. Sirolimus (SRL) is a nonnephrotoxic immunosuppressive agent. We retrospectively analyzed our experience with kidney transplant recipients who were converted from CNI to SRL. A total of 58 renal transplant recipients were converted from CNI to SRL. SRL was started at a dose of 0.075 mg/kg and, at the same time, CNI dose was reduced by 50% daily for 3 days. SRL trough levels were targeted between 8 and 12 ng/mL. When target trough levels were achieved, CNI was withdrawn. The main indications for switching were posttransplant malignancies (n = 32) and chronic allograft nephropathy (CAN) (n = 10). The mean time from transplantation to conversion was 84 ± 71 months. Mean serum creatinine level was 1.63 ± 0.52 mg/dL before conversion. Serum creatinine levels at the 1, 3, 6 months, and 1, 2, 3 years after conversion were 1.64 ± 0.58 mg/dL (P = 0.67), 1.52 ± 0.53 mg/dL (P = 0.414), 1.62 ± 0.62 mg/dL (P = 0.734), and 1.48 ± 0.58 mg/dL (P = 0.065), 1.58 ± 0.53 mg/dL (P = 0.854), 1.88 ± 0.77 mg/dL (P = 0.083), respectively. Daily proteinuria levels increased from 0.04 ± 0.11 g/day at baseline to 0.55 ± 1.33 g/day (P = 0.037) after conversion, in the responders group. In the nonresponders group, baseline proteinuria was 0.13 ± 0.25 g/day, and increased to 1.44 ± 2.44 g/day after conversion (P = 0.008). SRL was discontinued in 16 patients (31%) because of the occurrence of severe side effects. The proportion of patients remaining on SRL therapy over time was 43.1% at 1 year, 15.5% at 2 years after conversion, and 10.3% at 3 years after conversion. SRL conversion may be very useful in patients suffering from neoplasia; however, frequent side effects related with this intervention should be considered, and routine conversion from CNI to SRL to reduce nephrotoxicity should be discouraged.     

Treatment of Anemia in Renal Transplantation: Impact of a Stricter Application of Hemoglobin Targets

Objective

The CREATE and CHOIR studies showed a higher risk for cardiovascular events associated with hemoglobin (Hb) values >13 g/dL in patients with stage 3-4 chronic kidney disease. In 2007, a stricter policy on the use of erythropoietin (EPO) was adopted at our center, with an Hb target of 11 to 12 g/dL and withdrawal or reduction of EPO when Hb was >12.5 to 13 g/dL. This study was designed to evaluate this new approach.

Materials and Methods

The study included patients under follow-up at the transplant outpatient clinic on December 31, 2006 (n = 725), and December 31, 2007 (n = 768). Data were compared between the study populations concerning renal function, Hb, use of EPO, and associated costs.

Results

No significant differences in creatinine or Hb values were observed between the 2 groups (1.47 ± 0.6 vs 1.42 ± 0.9 mg/dL and 13.7 ± 1.5 vs 13.7 ± 1.6 g/dL, respectively). After implementation of the new protocol, the frequency of severe anemia (Hb <11 g/dL) increased (2% vs 4%; P = .10), the use of EPO decreased (22.1% vs 17.2%; P = .017), and the mean Hb of EPO-treated patients decreased (12.5 ± 1.4 vs 11.9 ± 1.0; P < .001). The Hb target (11-12 g/dL) was met in fewer than one third of patients, with no significant differences between the 2 study times.

Conclusions

A strict policy on EPO application reduces its use and the rate of patients with “excessive” Hb values (which are associated with increased cardiovascular risks), with an acceptable slight increase in severe anemia cases.     

Multilaboratory Study of Flow‐Induced Hemolysis Using the FDA Benchmark Nozzle Model

Multilaboratory in vitro blood damage testing was performed on a simple nozzle model to determine how different flow parameters and blood properties affect device‐induced hemolysis and to generate data for comparison with computational fluid dynamics‐based predictions of blood damage as part of an FDA initiative for assessing medical device safety. Three independent laboratories evaluated hemolysis as a function of nozzle entrance geometry, flow rate, and blood properties. Bovine blood anticoagulated with acid citrate dextrose solution (2–80 h post‐draw) was recirculated through nozzle‐containing and paired nozzle‐free control loops for 2 h. Controlled parameters included hematocrit (36 ± 1.5%), temperature (25°C), blood volume, flow rate, and pressure. Three nozzle test conditions were evaluated (n = 26–36 trials each): (i) sudden contraction at the entrance with a blood flow rate of 5 L/min, (ii) gradual cone at the entrance with a 6‐L/min blood flow rate, and (iii) sudden‐contraction inlet at 6 L/min. The blood damage caused only by the nozzle model was calculated by subtracting the hemolysis generated by the paired control loop test. Despite high intralaboratory variability, significant differences among the three test conditions were observed, with the sharp nozzle entrance causing the most hemolysis. Modified index of hemolysis (MIH_nozzle) values were 0.292 ± 0.249, 0.021 ± 0.128, and 1.239 ± 0.667 for conditions i–iii, respectively. Porcine blood generated hemolysis results similar to those obtained with bovine blood. Although the interlaboratory hemolysis results are only applicable for the specific blood parameters and nozzle model used here, these empirical data may help to advance computational fluid dynamics models for predicting blood damage.     

rPSGL‐Ig for Improvement of Early Liver Allograft Function: A Double‐Blind,Placebo‐Controlled,Single‐Center Phase II Study†

The selectin antagonist known as recombinant P‐selectin glycoprotein ligand IgG (rPSGL‐Ig) blocks leukocyte adhesion and protects against transplantation ischemia reperfusion injury (IRI) in animal models. This randomized (1:1) single‐center double‐blind 47‐patient phase 2 study with 6‐month follow‐up assessed rPSGL‐Ig's safety and impact on early graft function at 1 mg/kg systemic dose with pretransplant allograft ex vivo treatment in deceased‐donor liver transplant recipients. Safety was assessed in all patients, whereas efficacy was assessed in a prospectively defined per‐protocol patient set (PP) by peak serum transaminase (TA) and bilirubin values, and normalization thereof. In PP patients, the incidence of poor early graft function (defined as peak TA >2500 U/L or bilirubin >10 mg/dL), average peak liver enzymes and bilirubin, normalization thereof and duration of primary and total hospitalization trended consistently lower in the rPSGL‐Ig group compared to placebo. In patients with donor risk index above study‐average, normalization of aspartate aminotransferase was significantly improved in the rPSGL‐Ig group (p < 0.03). rPSGL‐Ig treatment blunted postreperfusion induction versus placebo of IRI biomarker IP‐10 (p < 0.1) and augmented cytoprotective IL‐10 (p < 0.05). This is the first clinical trial of an adhesion molecule antagonist to demonstrate a beneficial effect on liver transplantation IRI and supported by therapeutic modulation of two hepatic IRI biomarkers.     

New Generation Extracorporeal Membrane Oxygenation With MedTech Mag‐Lev,a Single‐Use,Magnetically Levitated,Centrifugal Blood Pump: Preclinical Evaluation in Calves

We have evaluated the feasibility of a newly developed single‐use, magnetically levitated centrifugal blood pump, MedTech Mag‐Lev, in a 3‐week extracorporeal membrane oxygenation (ECMO) study in calves against a Medtronic Bio‐Pump BPX‐80. A heparin‐ and silicone‐coated polypropylene membrane oxygenator MERA NHP Excelung NSH‐R was employed as an oxygenator. Six healthy male Holstein calves with body weights of about 100 kg were divided into two groups, four in the MedTech group and two in the Bio‐Pump group. Under general anesthesia, the blood pump and oxygenator were inserted extracorporeally between the main pulmonary artery and the descending aorta via a fifth left thoracotomy. Postoperatively, both the pump and oxygen flow rates were controlled at 3 L/min. Heparin was continuously infused to maintain the activated clotting time at 200–240 s. All the MedTech ECMO calves completed the study duration. However, the Bio‐Pump ECMO calves were terminated on postoperative days 7 and 10 because of severe hemolysis and thrombus formation. At the start of the MedTech ECMO, the pressure drop across the oxygenator was about 25 mm Hg with the pump operated at 2800 rpm and delivering 3 L/min flow. The PO₂ of the oxygenator outlet was higher than 400 mm Hg with the PCO₂ below 45 mm Hg. Hemolysis and thrombus were not seen in the MedTech ECMO circuits (plasma‐free hemoglobin [PFH] < 5 mg/dL), while severe hemolysis (PFH > 20 mg/dL) and large thrombus were observed in the Bio‐Pump ECMO circuits. Plasma leakage from the oxygenator did not occur in any ECMO circuits. Three‐week cardiopulmonary support was performed successfully with the MedTech ECMO without circuit exchanges. The MedTech Mag‐Lev could help extend the durability of ECMO circuits by the improved biocompatible performances.     

CD25 blockade in kidney transplant patients randomized to standard‐dose or high‐dose basiliximab with cyclosporine,or high‐dose basiliximab in a calcineurin inhibitor‐free regimen

An increased basiliximab dose may saturate T‐cell CD25 receptors in kidney transplant patients receiving calcineurin inhibitor (CNI)‐free immunosuppression. In a 12‐week study, 16 de novo kidney transplant patients were randomized to (i) 40 mg basiliximab with cyclosporine [n = 3] (controls), (ii) 80 mg basiliximab with cyclosporine [n = 6], or (iii) 80 mg basiliximab with everolimus (CNI‐free) [n = 7], all with mycophenolic acid and steroids. Recruitment was stopped prematurely due to increased biopsy‐proven acute rejection (BPAR) in the basiliximab 80 mg CNI‐free group. BPAR occurred in 1/3, 1/6, and 4/7 patients in the three treatment groups, respectively. The primary endpoint, area under the effect curve of CD25 saturation to week 12, was 8.4(1.6) % × weeks in the control group, 11.1(1.1) % × weeks with basiliximab 80 mg + cyclosporine, and 9.7(0.7) % × weeks in the basiliximab 80 mg CNI‐free group (P = 0.020 for basiliximab 80 mg + cyclosporine versus controls; P = 0.119 for basiliximab 80 mg CNI‐free versus controls). Although small patient numbers prohibit robust conclusions, these results suggest that doubling the cumulative basiliximab dose to 80 mg does not provide adequate immunosuppression during the first 3 months after kidney transplantation in the absence of CNI therapy (ClinicalTrials.gov number: NCT01596062).