Impact of CYP2D6 polymorphisms on endoxifen concentrations and breast cancer outcomes.

We investigated the impact of germline CYP2D6 genotyping done using the non-tumor specimen on endoxifen concentrations and/or clinical outcomes in breast cancer (BC) patients treated with tamoxifen in published studies. We evaluated published data from 13 001 patients in 29 studies. Mean±s.d. endoxifen concentrations were significantly lower in poor metabolizers (PM) versus extensive metabolizers (EM) (8.8±7.2 versus 22.3±11.8 ng ml-1; P<0.05). The PM status did not influence clinical outcomes in majority of the studies. However, only one study followed the Gaedigk activity scoring for phenotypic assignments, which predicted recurrence-free survival in CYP2D6 poor metabolizers. In two independent studies with 1676 patients, low endoxifen concentrations predicted poor BC-free survival. From our review of published data we found that standardization of CYP2D6 genotype-phenotype classification is needed in order to ensure effective evaluation of associations between CYP2D6 polymorphisms and endoxifen concentrations and BC outcomes. Universal implementation of this standardization classification system should be a priority among researchers and laboratories. Furthermore, additional clinical research is warranted to determine whether patients with CYP2D6 PM phenotypes or low endoxifen levels will have better clinical outcomes with increased tamoxifen dosing compared to standard dosing.

Charge disproportionation and the pressure-induced insulator-metal transition in cubic perovskite PbCrO3.

The perovskite PbCrO3 is an antiferromagnetic insulator. However, the fundamental interactions leading to the insulating state in this single-valent perovskite are unclear. Moreover, the origin of the unprecedented volume drop observed at a modest pressure of P = 1.6 GPa remains an outstanding problem. We report a variety of in situ pressure measurements including electron transport properties, X-ray absorption spectrum, and crystal structure study by X-ray and neutron diffraction. These studies reveal key information leading to the elucidation of the physics behind the insulating state and the pressure-induced transition. We argue that a charge disproportionation 3Cr(4+) → 2Cr(3+) + Cr(6+) in association with the 6s-p hybridization on the Pb(2+) is responsible for the insulating ground state of PbCrO3 at ambient pressure and the charge disproportionation phase is suppressed under pressure to give rise to a metallic phase at high pressure. The model is well supported by density function theory plus the correlation energy U (DFT+U) calculations.

Anomalous perovskite PbRuO3 stabilized under high pressure.

Perovskite oxides ABO3 are important materials used as components in electronic devices. The highly compact crystal structure consists of a framework of corner-shared BO6 octahedra enclosing the A-site cations. Because of these structural features, forming a strong bond between A and B cations is highly unlikely and has not been reported in the literature. Here we report a pressure-induced first-order transition in PbRuO3 from a common orthorhombic phase (Pbnm) to an orthorhombic phase (Pbn21) at 32 GPa by using synchrotron X-ray diffraction. This transition has been further verified with resistivity measurements and Raman spectra under high pressure. In contrast to most well-studied perovskites under high pressure, the Pbn21 phase of PbRuO3 stabilized at high pressure is a polar perovskite. More interestingly, the Pbn21 phase has the most distorted octahedra and a shortest Pb-Ru bond length relative to the average Pb-Ru bond length that has ever been reported in a perovskite structure. We have also simulated the behavior of the PbRuO3 perovskite under high pressure by first principles calculations. The calculated critical pressure for the phase transition and evolution of lattice parameters under pressure match the experimental results quantitatively. Our calculations also reveal that the hybridization between a Ru:t2g orbital and an sp hybrid on Pb increases dramatically in the Pbnm phase under pressure. This pressure-induced change destabilizes the Pbnm phase to give a phase transition to the Pbn21 phase where electrons in the overlapping orbitals form bonding and antibonding states along the shortest Ru-Pb direction at P > Pc.

Preoperative coronary calcium score is predictive of early postoperative cardiovascular complications in liver transplant recipients.

BACKGROUND: Coronary computed tomographic angiography (coronary CT) is a non-invasive test for diagnosis of cardiac function. Coronary calcium scores determined by coronary CT are associated with cardiovascular risk factors. However, no studies have investigated the association between coronary calcium scores and cardiovascular complications after liver transplantation (LT). We therefore evaluated the utility of preoperative coronary calcium scores for predicting early postoperative cardiovascular complications in LT recipients. METHODS: Between 2010 and 2012, 443 LT recipients were analysed retrospectively. Preoperative cardiovascular assessments, including coronary CT, were performed. A coronary calcium score >400 was defined as a positive finding. Predictive factors of early postoperative cardiovascular complications were evaluated by univariate and multivariate analyses. Major cardiovascular complications occurring during a period of 1 month after LT were noted. RESULTS: Of the 443 patients, 38 (8.6%) experienced one or more cardiovascular complications. Positive coronary CT findings were seen in 11 (2.5%) patients. In the multivariate analysis, a coronary calcium score >400 {odds ratio (OR)=4.62 [95% confidence interval (CI): 1.14-18.72], P=0.032} and female sex [OR=2.76 (1.37-5.57), P=0.005] were predictive of cardiovascular complications. CONCLUSIONS: A preoperative coronary calcium score of >400 predicted cardiovascular complications occurring 1 month after LT, suggesting that preoperative evaluation of coronary calcium scores could help predict early postoperative cardiovascular complications in LT recipients.

Effect of stroke volume variation-directed fluid management on blood loss during living-donor right hepatectomy: a randomised controlled study.

Reducing blood loss is beneficial in living liver donor hepatectomy. Although it has been suggested that maintaining a low central venous pressure is important, it is known that low stroke volume variation may be associated with increased blood loss. Therefore, we compared the effect on blood loss of 40 patients randomly assigned to a high stroke volume variation group (maintaining 10-20% of stroke volume variation) vs 38 patients in a control group (maintaining < 10% stroke volume variation) during living-donor right hepatectomy. Mean (SD) blood loss during donor hepatectomy was significantly lower in the high stroke volume variation group than in the control group: 476 (131) ml vs 836 (341) ml, respectively (p < 0.001). Blood pressure and peri-operative laboratory values did not differ between the two groups. However, in the high stroke volume variation group, central venous pressure values were also significantly lower. We were unable to disentangle the effects of stroke volume variation and central venous pressure, but our results confirm that the two together appear beneficial.

Repair of complex parastomal hernias.

Development of parastomal hernias (PH) is very common after stoma formation and carries a risk of subsequent bowel incarceration, obstruction and strangulation. The management of PH remains a challenge for the colorectal surgeon, and there are currently no standardized guidelines for the treatment of PH. Even more difficult is the management of complex parastomal hernias (CPH). We conducted a review of the literature to identify recent developments in the treatment of CPH, including analysis of the use of synthetic and biologic mesh prostheses, method of mesh placement and surgical approach.

Acute kidney injury after infrarenal abdominal aortic aneurysm surgery: a comparison of AKIN and RIFLE criteria for risk prediction.

BACKGROUND: Although both Acute Kidney Injury Network (AKIN) and risk, injury, failure, loss, and end-stage (RIFLE) kidney disease criteria are frequently used to diagnose acute kidney injury (AKI), they have rarely been compared in the diagnosis of AKI in patients undergoing surgery for infrarenal abdominal aortic aneurysm (AAA). This study investigated the incidence of, and risk factors for, AKI, defined by AKIN and RIFLE criteria, and compared their ability to predict mortality after infrarenal AAA surgery. METHODS: This study examined 444 patients who underwent infrarenal AAA surgery between January 1999 and December 2011. Risk factors for AKI were assessed by multivariable analyses, and the impact of AKI on overall mortality was assessed by a Cox's proportional hazard model with inverse probability of treatment weighting (IPTW). Net reclassification improvement (NRI) was used to assess the performance of AKIN and RIFLE criteria in predicting overall mortality. RESULTS: AKI based on AKIN and RIFLE criteria occurred in 82 (18.5%) and 55 (12.4%) patients, respectively. The independent risk factors for AKI were intraoperative red blood cell (RBC) transfusion and chronic kidney disease (CKD) by AKIN criteria, and age, intraoperative RBC transfusion, preoperative atrial fibrillation, and CKD by RIFLE criteria. After IPTW adjustment, AKI was related to 30 day mortality and overall mortality. NRI was 15.2% greater (P=0.04) for AKIN than for RIFLE criteria in assessing the risk of overall mortality. CONCLUSIONS: Although AKI defined by either AKIN or RIFLE criteria was associated with overall mortality, AKIN criteria showed better prediction of mortality in patients undergoing infrarenal AAA surgery.

Five-minute parameter of thromboelastometry is sufficient to detect thrombocytopenia and hypofibrinogenaemia in patients undergoing liver transplantation.

BACKGROUND: Early detection of coagulopathy is important to prevent bleeding during liver transplantation (LT). Rotation thromboelastometry (ROTEM(®)) provides the earliest parameter of clot amplitudes at 5 min (A5). We evaluated whether A5 correlates with platelet count (PLT) and fibrinogen concentration (Fib) and can predict thrombocytopenia and hypofibrinogenaemia in hypocoagulable patients undergoing living-donor LT (LDLT). METHODS: A total of 3446 retrospective ROTEM(®) measurements, including 1139 EXTEM, 1182 INTEM, and 1125 FIBTEM, with simultaneously measured PLT and Fib, were analysed during LDLT in 239 patients. The correlations between A5 and maximum clot firmness (MCF) index, PLT, and Fib were calculated. Receiver operating characteristic analysis with area under the curve (AUC) was used to assess A5 thresholds predictive of PLT and Fib. RESULTS: The median PLT was 47 000 mm(-3) and the median Fib was 100 mg dl(-1) during LDLT. The A5 parameters of EXTEM (A5EXTEM) and INTEM (A5INTEM) were highly correlated with MCF (r=0.96 and r=0.95, respectively), PLT (r=0.76 and r=0.77, respectively), and Fib (r=0.63 and r=0.64, respectively). A5 of FIBTEM (A5FIBTEM) was also correlated with MCF (r=0.91) and Fib (r=0.75). A5EXTEM thresholds of 15 and 19 mm predicted PLT<30 000 mm(-3) (AUC=0.90) and <50 000 mm(-3) (AUC=0.87), respectively, whereas A5FIBTEM 4 mm predicted Fib<100 mg dl(-1) (AUC=0.86). Biases from A5EXTEM and A5FIBTEM to their MCFs were 16.4 and 1.3 mm, respectively. CONCLUSIONS: A5 as an early variable of clot firmness is effective in detecting critically low PLT and Fib. A5 can therefore be a reliable fast index guiding transfusion therapy in hypocoagulable patients undergoing LDLT.

Cost of practice in a tertiary/quaternary referral center: is it sustainable?

BACKGROUND: Third-party payers are moving toward a bundled care payment system. This means that there will need to be a warranty cost of care-where the cost of complexity and complication rates is built into the bundled payment. The theoretical benefit of this system is that providers with lower complication rates will be able to provide care with lower warranty costs and lower overall costs. This may also result in referring riskier patients to tertiary or quaternary referral centers. Unless the payment model truly covers the higher cost of managing such referred cases, the economic risk may be unsustainable for these centers. METHODS: We took the last seven patients that were referred by other surgeons as "too high risk" for colectomy at other centers. A contribution margin was calculated using standard Medicare reimbursement rates at our institution and cost of care based on our administrative database. We then recalculated a contribution margin assuming a 3 % reduction in payment for a higher than average readmission rate, like that which will take effect in 2014. Finally, we took into account the cost of any readmissions. RESULTS: Seven patients with diagnosis related group (DRG) 330 were reviewed with an average age of 66.8 ± 16 years, American Society of Anesthesiologists score 2.3 ± 1.0, body mass index 31.6 ± 9.8 kg/m(2) (range 22-51 kg/m(2)). There was a 57 % readmission rate, 29 % reoperation rate, 10.8 ± 7.7 day average initial length of stay with 14 ± 8.6 day average readmission length of stay. Forty-two percent were discharged to a location other than home. Seventy-one percent of these patients had Medicare insurance. The case mix index was 2.45. Average reimbursement for DRG 330 was $17,084 (based on Medicare data) for our facility in 2012, with the national average being $12,520. The total contribution margin among all cases collectively was -$19,122 ± 13,285 (average per patient -$2,731, range -$21,905-$12,029). Assuming a 3 % reimbursement reduction made the overall contribution margin -$22,122 ± 13,285 (average -$3,244). Including the cost of readmission in the variable cost made the contribution margin -$115,741 ± 16,023 (average -$16,534). CONCLUSIONS: Care of high-risk patients at tertiary and quaternary referral centers is a very expensive proposition and can lead to financial ruin under the current reimbursement system.

Serum metabolomics reveals pathways and biomarkers associated with asthma pathogenesis.

BACKGROUND: Asthma is a chronic inflammatory disease caused by complex interactions of genetic, epigenetic, and environmental factors. For this reason, new approaches are required to clarify the pathogenesis of asthma by systemic review. OBJECTIVE: We applied a (1)H-NMR metabolomics approach to investigate the altered metabolic pattern in sera from patients with asthma and sought to identify the mechanism underlying asthma and potential biomarkers. METHOD: A global profile of sera from patients with asthma (n = 39) and controls (n = 26) was generated using (1)H-NMR spectroscopy coupled with multivariate statistical analysis. Endogenous metabolites in serum were rapidly measured using the target-profiling procedure. RESULTS: Multivariate statistical analysis showed a clear distinction between patients with asthma and healthy subjects. Sera of asthma patients were characterized by increased levels of methionine, glutamine, and histidine and by decreased levels of formate, methanol, acetate, choline, O-phosphocholine, arginine, and glucose. The metabolites detected in the sera of patients with asthma are involved in hypermethylation, response to hypoxia, and immune reaction. Furthermore, the levels of serum metabolites from patients with asthma correlated with asthma severity; in particular, lipid metabolism was altered in patients with lower forced expiratory volume in 1 s percentage (FEV(1)%) predicted values. In addition, potential biomarkers showed strong predictive power in ROC analysis, and the presence of asthma in external validation models was predicted with high accuracy (90.9% for asthma and 100% for control subjects). CONCLUSION & CLINICAL RELEVANCE: These data showed that (1)H-NMR-based metabolite profiling of serum may be useful for the effective diagnosis of asthma and a further understanding of its pathogenesis.

Lactate and liver function tests after living donor right hepatectomy: a comparison of solutions with and without lactate.

BACKGROUND: Hyperlactatemia can predict the prognosis of patients undergoing liver resection. The effects of lactated Ringer's solution on liver function have not been evaluated in patients undergoing major liver resection. We therefore compared the effects of two different crystalloid solutions, with and without lactate, on liver function test data and serum lactate level in living donors undergoing right hepatectomy. METHODS: A total of 104 donors undergoing right hepatectomy for liver transplantation were randomly allocated to receive lactated Ringer's (LR) solution (n=52) or Plasmalyte (n=52). Anesthetic and fluid management were standardized. Acid-base status, lactate concentration, and liver function tests were analyzed at predetermined time points during the first 5 post-operative days. RESULTS: The lactate concentrations were significantly higher in the LR group than in the Plasmalyte group 1 h after hepatectomy [4.2 (3.2-5.7) vs. 3.3 (2.6-4.6) mmol/l; P=0.005, median (interquartile ranges)]. In addition, the nadir concentration of albumin was significantly lower and the peak total bilirubin concentration and prothrombin time were significantly higher in the LR group compared with the Plasmalyte group. However, these changes in the LR group subsided within the first or second post-operative days, without apparent complications or prolongation of hospital stay. Post-operative peak concentrations of lactate were not correlated with nadir albumin concentration, peak bilirubin, or peak prothrombin time, in either group. CONCLUSION: This prospective randomized study showed that non-lactate-containing crystalloid solution may have important advantages over LR solution, concerning lactate and liver profiles, in living donors undergoing right hepatectomy.

Association between central venous pressure and blood loss during hepatic resection in 984 living donors.

BACKGROUND: Although low central venous pressure (CVP) anesthesia has been used to minimize blood loss during hepatectomy, the efficacy of this technique remains controversial. We therefore assessed the association between blood loss and CVP during hepatic resection, and examined significant determinants associated with intraoperative hemorrhage during hepatectomy in living donors. METHODS: Between April 2004 and April 2008, 984 living donors who underwent a hepatic resection were assessed retrospectively. Univariate and multivariate analyses were performed to explore the relationships between intraoperative blood loss and several variables including CVP. RESULTS: The mean intraoperative blood loss was 691.3 +/- 365.5 ml. Only four donors required packed red blood cell transfusions (mean, 1.5 U). The mean duration of hepatic resection was 92.1 +/- 26.3 min. The mean, maximum, and minimum values of CVP measured during hepatectomy were 4.6 +/- 1.7, 5.3 +/- 1.8, and 4.0 +/- 1.8 mmHg, respectively, and were not significantly correlated with intraoperative blood loss. On multivariate analysis, predictors of hemorrhage were liver fatty change, gender, and body weight, but none of the mean CVP, surgeons, anesthesiologists, anesthesia duration, resected liver volume, hepatectomy type, systolic blood pressure, heart rate, or body temperature were significant. CONCLUSIONS: CVP during hepatic resection was not associated with intraoperative blood loss in living liver donors, suggesting that CVP may not be an important factor in predicting blood loss during hepatectomy in healthy subjects.

Using 100% oxygen does not alter the cardiovascular autonomic regulation during non-invasively simulated haemorrhage in healthy volunteers.

We tested the effect of 100% oxygen on heart rate (HR), arterial blood pressure (ABP), cardiac output (CO), stroke volume (SV), total peripheral resistance (TPR), HR variability (HRV), systolic blood pressure variability (SBPV) and baroreflex sensitivity (BRS) in 20 healthy volunteers during simulated haemorrhage induced by -40 mmHg lower body negative pressure (LBNP). HRV in the high frequency region (HRV HF), BRS, ABP and TPR were significantly increased, SBPV in the low frequency region (SBPV LF), CO and SV were unchanged, and HR was significantly decreased by 100% oxygen administration during normovolaemia. HRV HF, BRS, CO and SV were significantly decreased, SBPV LF and ABP were unchanged, and HR and TPR were significantly increased by LBNP during 21% or 100% oxygen administration. There were no significant differences in cardiovascular autonomic and haemodynamic responses to LBNP during 21% or 100% oxygen administration, suggesting that 100% oxygen does not alter normal cardiovascular autonomic responses during simulated haemorrhage.

Pretransplantation Cystatin C, but not Creatinine, Predicts 30-day Cardiovascular Events and Mortality in Liver Transplant Recipients With Normal Serum Creatinine Levels.

BACKGROUND: The connection between renal dysfunction and cardiovascular dysfunction has been consistently shown. In patients with liver cirrhosis, renal dysfunction shows a tight correlation with prognosis after liver transplantation (LT); therefore, precise renal assessment is mandatory. Cystatin C, a sensitive biomarker for assessing renal function, has shown superiority in detecting mild renal dysfunction compared to classical biomarker creatinine. In this study, we aimed to compare cystatin C and creatinine in predicting 30-day major cardiovascular events (MACE) and all-cause mortality in LT recipients with normal serum creatinine levels. PATIENTS AND METHODS: Between May 2010 and October 2015, 1181 LT recipients (mean Model for End-stage Liver Disease score 12.1) with pretransplantation creatinine level ≤1.4 mg/dL were divided into tertiles according to each renal biomarker. The 30-day MACE was a composite of troponin I >0.2 ng/mL, arrhythmia, congestive heart failure, death, and cerebrovascular events. RESULTS: The highest tertile of cystatin C (≥0.95 mg/L) was associated with a higher risk for a 30-day MACE event (odds ratio: 1.62; 95% confidence interval: 1.07 to 2.48) and higher risk of death (hazard ratio: 1.96; 95% confidence interval: 1.04 to 3.67) than the lowest tertile (<0.74 mg/L) after multivariate adjustments. However, the highest tertile of creatinine level showed neither increasing MACE event rate nor worse survival rate compared with the lowest tertile (both insignificant after multivariate adjustment). CONCLUSIONS: Pretransplantation cystatin C is superior in risk prediction of MACE and all-cause mortality in LT recipients with normal creatinine, compared to creatinine. It would assist further risk stratification which may not be detected with creatinine.

Application of the Revised Cardiac Risk Index to the Model for End-Stage Liver Disease Score Improves the Prediction of Cardiac Events in Patients Undergoing Liver Transplantation.

INTRODUCTION: Although the revised cardiac risk index (RCRI) is a useful tool for estimating the risk of postoperative cardiac events, whether it improves the prediction of cardiac events in patients undergoing liver transplantation (LT) has not been sufficiently demonstrated. METHODS: We retrospectively analyzed 1429 patients who underwent LT. Cardiac events were defined as myocardial infarction, death, or combined events within 30 days after surgery. The RCRI was defined as the number of independent predictors including high-risk surgery, ischemic heart disease, congestive heart failure, cerebrovascular disease, insulin treatment, and creatinine level >2 mg/dL. Multivariate logistic regression analysis was performed to identify factors independently associated with cardiac events. The additive predictability of RCRI for the Model for End-Stage Liver Disease (MELD) score was assessed using receiver operating characteristic curve analysis. RESULTS: Forty-four (3.1%) cardiac events occurred within 30 days after surgery. Both the MELD score (adjusted odds ratio [aOR], 1.05; P = .005) and RCRI (aOR, 4.35; P < .001 for RCRI score 2; aOR, 6.27; P = .009 for RCRI score 3 compared with RCRI score 1) independently predicted postoperative 30-day cardiac events. The model with MELD score plus RCRI was significantly more predictive for postoperative 30-day cardiac events than the model with MELD score alone (C-statistics 0.800 vs 0.757; P = .030). CONCLUSIONS: For preoperative risk stratification, RCRI showed additive value to MELD score in predicting postoperative 30-day cardiac events after LT.

Diabetes With or Without Hypertension Does Not Affect Graft Survival and All-cause Mortality After Liver Transplant: A Propensity Score Matching Analysis.

BACKGROUND: Many studies have reported the negative influence of diabetes and hypertension on morbidity and mortality in the general population. In liver transplantation (LT) recipients, prevalence of nonalcoholic fatty liver disease and metabolic syndrome is increasing. Hence, concerns over the negative influence of metabolic syndrome, including diabetes and hypertension, are growing. However, there have been few studies about the outcomes of LT recipients with diabetes with/without hypertension. We aimed to evaluate the impact of diabetes with/without hypertension on the outcomes of LT. METHODS: Between May 2010 and October 2015, 814 LT recipients (median age, 51 [46-55] years; median MELD score, 13 [9-18]), without overt cardiovascular disease were retrospectively evaluated. To rigorously adjust for clinically confounding factors, a 1:2 propensity score matching analysis was performed. Kaplan-Meier survival curves and Cox proportional hazard regression analysis were performed to examine the association between diabetes with/without hypertension and all-cause mortality or graft survival rate. RESULTS: There were 77 (9.5%) graft failures and 71 (8.7%) deaths during a median follow-up of 2.4 years. After 1:2 matching of 173 (21.3%) diabetic patients, no significant differences were evident in graft survival rate (log-rank test, P = .46; and hazard ratio [HR], 1.06; 95% confidence interval [CI], 0.55-2.06; P = .865) and all-cause mortality (log-rank test, P = .59; and HR, 1.06; 95% CI, 0.55-2.06; P = .727). Separate 1:2 matching was applied to a subgroup of 43 (5.3%) patients with diabetes and hypertension. This matching also showed no difference in graft survival rate (log-rank test, P = .45; and HR, 1.35; 95% CI, 0.43-4.27; P = .613) and all-cause mortality (log-rank test, P = .25; and HR, 1.87; 95% CI, 0.54-6.50; P = .325). CONCLUSION: Diabetes with/without hypertension does not have an impact on graft survival rate or all-cause mortality in LT recipients.

Brief Episodes of Newly Developed Intraoperative Atrial Fibrillation Predicts Worse Outcomes in Adult Liver Transplantation.

BACKGROUND: Although patients undergoing liver transplantation (LT) are frequently exposed to predisposing factors of atrial fibrillation (AF) such as autonomic imbalance, surgical stress, and elevated catecholamine levels, the occurrence of intraoperative AF (IOAF) has not been fully examined in LT candidates. METHODS: Data from 1059 patients who underwent adult LT from 2006 to 2010 were analyzed. Among patients with preoperative normal sinus rhythm, the incidence, prognosis, and detailed characteristics of newly developed IOAF were assessed. Their risk factors and clinical implication, including hepatic graft survival and mortality, were also examined. RESULTS: Thirteen (1.2%) cases of AF newly developed intraoperatively. A higher Model for End-Stage Liver Disease score (adjusted odds ratio, 1.077 [95% confidence interval, 1.015-1.143]; P = .015) and fulminant hepatic failure (adjusted odds ratio, 6.844 [95% CI, 1.944-24.096]; P = .003) were associated with its occurrence. Eight cases of newly developed AF occurred immediately after hepatic graft reperfusion; the other 3 cases occurred during the pre-anhepatic or anhepatic phase. The majority of patients (9 cases) experienced only brief episodes of AF lasting <1 hour. Despite all patients with newly developed AF eventually converting to sinus rhythm within 1 week after surgery, the episode of IOAF was independently associated with mortality (adjusted hazard ratio, 5.097 [95% confidence interval, 2.189-11.868]; P < .001) after adjustment for Model for End-Stage Liver Disease score. CONCLUSIONS: For LT recipients, even a brief episode of newly developed IOAF seems to be an important prognosticator, regardless of AF duration.

Prevalence of Antiphospholipid Antibody Positivity and Association of Pretransplant Lupus Anticoagulant Positivity With Early Allograft Dysfunction in Liver Transplantation.

BACKGROUND: Antiphospholipid antibodies (aPL), including anticardiolipin (aCL), anti-ß2-glycoprotein I (anti-ß2GPI), and lupus anticoagulant (LA) antibodies, are frequently found in liver cirrhosis and associated with splanchnic vein thrombosis. Although the risk factors of early allograft dysfunction (EAD) are known, the association between EAD and aPL has been poorly investigated. We hypothesized that LA, potent aPL with thrombotic potential, may be associated with EAD development after living donor liver transplantation (LDLT). METHODS: Data of 719 patients who underwent LDLT from February 2014 to June 2016 at our center were retrospectively collected and analyzed. Patients were divided into 2 groups according to the positivity of LA screening test (LA group [n = 148] vs no-LA group [n = 571]). Risk factors for EAD were investigated using multivariable regression analysis and inverse probability of treatment weighting (IPTW) of propensity scores. RESULTS: The prevalence of LA screening positivity, confirmatory test positivity, and EAD was 20.6%, 1.1%, and 11.3%, respectively. aCL positivity rate was 7.5% and anti-ß2GPI positivity rate was 7.0%. The EAD prevalence in LA and no-LA group was 25.7% and 7.5%, respectively. However, multivariable and IPTW analyses showed no association between EAD and LA screening positivity (P = .263 and P = .825, respectively), although a significant association was found in univariate analysis (odds ratio, 4.242; P < .001). Model for End-stage Liver Disease score, operation time, and C-reactive protein level remained significant after multivariable analysis. CONCLUSION: A positive LA screening test result was associated with EAD only in the univariate analysis. Inflammation, based on C-reactive protein level, was more important for EAD development.

Prediction of Fluid Responsiveness by a Non-invasive Respiratory Systolic Time Interval Variation Using Heart Sound Signals in Recipients Undergoing Liver Transplantation.

BACKGROUND: The fluid management of cirrhotic patients undergoing liver transplantation (LT) is challenging. Phonocardiography, a graphic recording of heart sounds, provides valuable information concerning heart function and hemodynamic condition. We assessed whether the systolic time interval (STI) and its respiratory variation could predict fluid responsiveness in cirrhotic patients undergoing LT. METHODS: Thirty LT recipients who needed volume expansion were included. The fluid challenge consisted of 500 mL 5% albumin administered over a period of 10 minutes. STI was measured as the time interval between the maximal amplitude of each heart sound corrected with the corresponding RR interval (cSTI). The respiratory variation in STI (STV) induced by mechanical ventilation was calculated. Responders were defined as those showing a ≥10% increase in stroke volume index after volume expansion. RESULTS: In all, 14 of the 30 patients were responders. Significant increases in cSTI were observed after volume expansion in both responders (P < .001) and non-responders (P = .008). Responders showed significant decreases in STV (11.1% ± 4.3% vs 6.1% ± 2.6%, P < .001) after fluid loading, whereas STV in non-responders remained unchanged (6.4% ± 2.6% vs 6.4% ± 4.2%, P = .86). A cut-off value of ≥7.5% STV from baseline could predict fluid responsiveness with an area under the receiver operating characteristic curve of 0.804 (95% confidence interval, 0.618-0.925). CONCLUSIONS: Intra-operative STV can predict fluid responsiveness in patients undergoing LT. Beat-to-beat monitoring of STI and STV may be useful as a non-invasive hemodynamic index and for fluid management.

Benefits of Intraoperative Continuous Renal Replacement Therapy During Liver Transplantation in Patients With Renal Dysfunction.

BACKGROUND: Comparative outcomes of continuous renal replacement therapy during liver transplantation have not been investigated. We retrospectively compared the outcomes of intraoperative continuous renal replacement therapy with those of non-dialytic conservative treatment in patients with pretransplant renal dysfunction. METHODS: We analyzed 240 transplantation patients with preoperative renal dysfunction (estimated glomerular filtration rate <60 mL/min/1.73 m2). RESULTS: Compared with the non-dialytic conservative treatment group (n = 98), the intraoperative continuous renal replacement therapy group (n = 142) experienced more severe critical illness (as indicated by Model for End-Stage Liver Disease score) and more severe preoperative renal dysfunction, as well as more frequent hepatic encephalopathy, ventilatory care, and intensive care unit admission (P < .005). There were also worse outcomes regarding patient survival, graft survival, recovery of renal function, and postoperative complications. However, the intraoperative continuous renal replacement therapy group significantly escaped volume overload (adjusted odds ratio, 0.396; 95% confidence interval, 0.223-0.703; P = .002) and unnecessary changes in serum sodium concentration ≥10 mmol/L during surgery (adjusted odds ratio, 0.208; 95% confidence interval, 0.065-0.665; P = .008). CONCLUSIONS: Considering the more severe critical illness of the intraoperative continuous renal replacement therapy group but the low frequency of volume overload and serum sodium fluctuation, intraoperative continuous renal replacement therapy could be useful during liver transplantation in critically ill patients with renal dysfunction. Randomized, controlled studies that could demonstrate outcome benefits and indications of intraoperative continuous renal replacement therapy during liver transplantation are needed.