Intraoperative fluid management can be difficult; intravenous fluids containing only crystalloids, such as Hartmann’s solution or “normal saline” may worsen ascites and peripheral edema but have little effect on intravascular volumes.38 Baseline blood pressure and serum sodium in chronic liver disease are often significantly lower than in other patients, and are generally not corrected by administration of intravenous saline. Instead, blood volume and fluid support should be in the form of a volume CB-839 mouse expander such as hemaccel, gelofusine, Voluven or concentrated albumin. Perioperative antibiotics that cover most Gram-negative

bacteria, such as a third generation cephalosporin, should be given if

there is ascites, to reduce the risk of bacterial peritonitis from the bacteremia that may occur during the surgical procedure. A high-dependency unit bed should be booked for the first 24 h. The postoperative period may see the development of ascites (particularly with injudicious administration of normal saline), infection, hemorrhage or encephalopathy.6 It is important to maintain salt restriction with both intravenous fluid replacement and oral intake.38 Intravascular volume and renal function should also be monitored and supported with volume expanders as required.6 Constipation should be prevented with the early introduction of lactulose or other means such as enemas, to reduce the chance of encephalopathy. The dosage interval of analgesics or sedatives should be increased, and/or a smaller dose given, as the liver’s capacity buy Neratinib to remove medications may be impaired, particularly those metabolized via cytochrome P450 enzymes. Cumulative 上海皓元 dosing may easily result in overdose or hepatic encephalopathy. The greater the liver dysfunction, the greater the impairment in drug metabolism,39 and this is true of simple analgesics

such as paracetamol, non-steroidal anti-inflammatory agents, and opioid analgesics.39 Fentanyl opioid is preferred, because although it is hepatically cleared there are no active metabolites. However, it may accumulate in the fat if used for several days.40 Any change in conscious state, mood, personality or neurological signs, should be considered to be encephalopathy and managed in the usual way.41 It should be remembered that these complications may occur several days or a few weeks postoperatively. There are no evidence-based guidelines for management of the cirrhotic patient undergoing a surgical procedure. There is only limited published information, and available literature is entirely from retrospective audits, with no prospective studies. The care of the patient with cirrhosis needs to be individualized and this is best done with a preoperative assessment and management plan by a physician experienced in managing chronic liver disease.

We hypothesized that patient empowerment prompted by an SVR could lead these patients to consider comorbidities such as alcohol intake, and in this way could decrease hepatic and/or global morbidity or mortality.3 We conducted a pilot study aimed at evaluating the impact of SVR on detoxification in 40 alcoholic heavy drinkers (26 men, 14 women; mean age, 46 years; mean daily quantity, 87 g alcohol) infected with HCV. All patients presented an abuse or dependence according to DSM-IV

classification and a CAGE questionnaire score ≥2 at baseline. Thirty-three patients (20 genotypes 1/4, 13 genotypes 2/3) were treatment-naïve. Pegylated Selleckchem NVP-BGJ398 interferon-α and ribavirin were initiated simultaneously with a treatment course for alcohol PS-341 nmr detoxification according to the recommendations (48 weeks for genotypes 1/4, 24 weeks for genotypes 2/3, 72 weeks for nonresponders). The patients were regularly followed up by a team composed of a nurse, a psychiatrist, a psychologist, and a hepatologist. Six patients discontinued treatment (two for severe anemia, one for hepatocarcinoma, and three for psychiatric side effects [depression, massive alcohol consumption]). For

treatment-naïve patients, the SVR observed on intention-to-treat and per-protocol analysis was 40% and 50%, respectively, for genotypes 1/4 and 69% and 82%, respectively, for genotypes 2/3. At the end of the study, 55% of the 40 patients were weaned off alcohol; among these, 71% of the treatment-naïve patients with SVR were also weaned off alcohol, whereas only 37% of

nonresponders were weaned off alcohol (P = 0.056). At the end of the study, the Hamilton’s score significantly improved in patients with an SVR (P = 0.07). Treatment of HCV concomitant with a program of alcohol weaning was possible in heavy drinkers when subjected to effective psychiatric evaluation. Therefore, our results and the Innes et al. data fit well with the proposed hypothesis3: that patients achieving an SVR are more prone to change their way of life and to control some pathological factors, such as excessive alcohol consumption. Régine Truchi*, 上海皓元医药股份有限公司 Eve Gelsi*, Faredj Cherikh*, Albert Tran*, Patrice Couzigou*, * Service Hépato-Gastroenterology, Hôpital du Haut Leveque, Pessac, France. “
“We thank Dr. Schramm and Dr. Lohse for their generous comments regarding our review and for sharing their experience with malignant gallbladder disease in primary sclerosing cholangitis (PSC) patients. As noted, our recommendations do differ slightly from the European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD) guidelines, which recommend prompt cholecystectomy for gall bladder polyps of any size in PSC patients. Our review (fig. 2) also recommends consideration of prompt cholecystectomy in PSC patients with gall bladder polyps of any size in patients with good liver function.

We hypothesized that patient empowerment prompted by an SVR could lead these patients to consider comorbidities such as alcohol intake, and in this way could decrease hepatic and/or global morbidity or mortality.3 We conducted a pilot study aimed at evaluating the impact of SVR on detoxification in 40 alcoholic heavy drinkers (26 men, 14 women; mean age, 46 years; mean daily quantity, 87 g alcohol) infected with HCV. All patients presented an abuse or dependence according to DSM-IV

classification and a CAGE questionnaire score ≥2 at baseline. Thirty-three patients (20 genotypes 1/4, 13 genotypes 2/3) were treatment-naïve. Pegylated LY2835219 interferon-α and ribavirin were initiated simultaneously with a treatment course for alcohol Rapamycin detoxification according to the recommendations (48 weeks for genotypes 1/4, 24 weeks for genotypes 2/3, 72 weeks for nonresponders). The patients were regularly followed up by a team composed of a nurse, a psychiatrist, a psychologist, and a hepatologist. Six patients discontinued treatment (two for severe anemia, one for hepatocarcinoma, and three for psychiatric side effects [depression, massive alcohol consumption]). For

treatment-naïve patients, the SVR observed on intention-to-treat and per-protocol analysis was 40% and 50%, respectively, for genotypes 1/4 and 69% and 82%, respectively, for genotypes 2/3. At the end of the study, 55% of the 40 patients were weaned off alcohol; among these, 71% of the treatment-naïve patients with SVR were also weaned off alcohol, whereas only 37% of

nonresponders were weaned off alcohol (P = 0.056). At the end of the study, the Hamilton’s score significantly improved in patients with an SVR (P = 0.07). Treatment of HCV concomitant with a program of alcohol weaning was possible in heavy drinkers when subjected to effective psychiatric evaluation. Therefore, our results and the Innes et al. data fit well with the proposed hypothesis3: that patients achieving an SVR are more prone to change their way of life and to control some pathological factors, such as excessive alcohol consumption. Régine Truchi*, 上海皓元医药股份有限公司 Eve Gelsi*, Faredj Cherikh*, Albert Tran*, Patrice Couzigou*, * Service Hépato-Gastroenterology, Hôpital du Haut Leveque, Pessac, France. “
“We thank Dr. Schramm and Dr. Lohse for their generous comments regarding our review and for sharing their experience with malignant gallbladder disease in primary sclerosing cholangitis (PSC) patients. As noted, our recommendations do differ slightly from the European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD) guidelines, which recommend prompt cholecystectomy for gall bladder polyps of any size in PSC patients. Our review (fig. 2) also recommends consideration of prompt cholecystectomy in PSC patients with gall bladder polyps of any size in patients with good liver function.

Reijnders – Speaking and Teaching: Bristol Myers-Squibb, Gilead Tania M. Welzel – Advisory Committees or Review Panels: Novartis Heiner Wedemeyer – Advisory Committees or Review Panels: Transgene, MSD, Roche, Gilead, Abbott, BMS, Falk; Grant/Research Support: MSD, Novartis, Gilead, Roche, Abbott; Speaking and Teaching: BMS, MSD, Novartis, ITF Maria Buti – Speaking and Teaching: MSD, Gilead, BMS, Janseen Fabien Zoulim – Advisory Committees or Review Panels: Gilead; Consulting:

Roche; Grant/Research Support: Gilead, Scynexis, Roche; Speaking and Teaching: Novartis, Roche, Janssen, Bristol Myers Squibb, Gilead Stephen Locarnini – Consulting: Gilead, Bristol-Myers Squibb, Merck Sharpe and Dohme; Employment: Melbourne Health Harry L. Janssen – Consulting: Abbott, Bristol Myers Squibb, Debio, Gilead Sciences, selleck products Merck, Medtronic, Novartis, Midostaurin Roche, Santaris; Grant/Research Support: Anadys, Bristol Myers Squibb, Gilead Sciences, Innogenetics, Kirin, Merck, Medtronic, Novartis, Roche, Santaris The following people have nothing to disclose: Pauline Arends, Massimo Fasano, Charles A. Boucher, Bettina E. Hansen, Annemiek A. van der Eijk Background: Studies have shown that HBeAg/HBsAg quantifications are predictors of sustained response to PEG-IFN. Little was known about the predictive values

of HBeAg/HBsAg levels in Chinese CHB patients receiving PEG-IFN α-2b therapy. Previously we conducted a trial to evaluate PEG-IFN α-2b efficacy for Chinese HBeAg positive CHB patients (NCT 00536263). Totally 220 Chinese patients were enrolled to receive PEG-IFN α-2b 1.5μg/kg/week for 48 weeks. The aim of this study was to evaluate HBeAg/HBsAg for the prediction of sustained response to 48 weeks Peginterferon α-2b therapy isometheptene in Chinese HBeAg-positive patients.Methods: Sustained response was defined as HBeAg seroconversion, HBV DNA<2,000 IU/mL and ALT normalization 24 weeks post-treatment. HBsAg and HBeAg levels were analyzed from samples collected at baseline, week 12, week 24, week 48 and follow-up 24 weeks. HBsAg/HBeAg levels were

quantified using the Roche Elecsys assays. Week 12 and week 24 HBsAg/HBeAg decline were calculated. Receiver operating characteristic (ROC) curves and area under curves (AUC) were used to assess predictive values of variables. The optimal cut-off values of the predictors were determined and sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for each predictor.Results: Samples of 181 Chinese patients were available for analysis, among which 30 patients had a sustained response (1 6.6%) AUC and best cut-off value of possible predictors were listed in the table. Week 24 HBeAg level, week 24 HBeAg decline and week 24 HBsAg level provided better predictions of sustained response. At week 24, the HBeAg cutoff value of 1.1000 PEIU/ml had sensitivity and NPV of 76.67% and 94.53%; HBeAg decline cut-off value of 11.

RESULTS: Analysis of the entire group indicated that 76% achieved SVR. In 63 patients treated with TVR, who showed non response to prior treatment, a higher proportion of patients undetected PI-resistant variants Compound Library clinical trial at the baseline (54%) achieved SVR than that of patients detected resistant variants at the baseline (0%). In patients treated with TVR, multivariate analysis identified PEG-IFN dose (<1.3 μg/ kg), IL28B rs8099917 (genotype non TT), TVR-resistant variants of aa54 at the baseline (Detection), response to prior treatment (Non response), and leukocyte count (<5,000/mm3) as significant

pretreatment factors of detection of TVR-resistant variants at the re-elevation of viral load. 12 patients (6 patients of TVR, and 6 of SMV), who did not achieve SVR, were

tested for resistant variants over time by ultra-deep sequencing. 21 of 30 resistant variants (70%), detected at re-elevation of viral load, were de novo resistant variants. 19 of 21 de novo resistant variants (90%) become undetectable over time. Furthermore, 6 patients (4 patients of TVR, and 2 of SMV), who did not achieve SVR by the first course of triple therapy, received the Birinapant second course of the triple therapy. 4 of 6 patients (67%) achieved SVR by the second course, despite the persistence of very high frequency variants or the past history of the emergence of variants by ultra-deep sequencing. CONCLUSIONS: This study indicated that PI-resistant variants at the re-elevation of viral load could be predicted by the combination of host, viral, and treatment factors. Resistant variants at the baseline might partly affect treatment efficacy, especially non response to prior treatment. The emergence of PI-resistant variants after the start of treatment could not be predicted at baseline,

and the majority of de novo resistant variants become undetectable over time. Disclosures: Norio Akuta – Patent Held/Filed: selleck kinase inhibitor SRL. Inc. Hiromitsu Kumada – Speaking and Teaching: Bristol-Myers Squibb,Pharma International, MSD, Dainippon Sumitomo, Tanabe Mitsubishi, Ajinomoto The following people have nothing to disclose: Fumitaka Suzuki, Yushi Sorin, Taito Fukushima, Yusuke Kawamura, Hitomi Sezaki, Yoshiyuki Suzuki, Tetsuya Hosaka, Masahiro Kobayashi, Satoshi Saitoh, Mariko Kobayashi, Yasuji Arase, Kenji Ikeda Background: Sofosbuvir was approved for the use in Germany January 2014. Recommendation in Germany (BNG/DGVS) voted for the triple therapy with PEG-IFN, Ribavirin(Riba) and Sofosbuvir(SOF) with a duration of 12 weeks. Dual therapy with SOF and Riba should be limited to special cases.

12, 15, 20, 25 Interestingly, the effect of the altered cytokine milieu generated by LPS-treated TK−/− Kupffer cells was more toxic to mouse hepatocytes in vitro compared to TK+/+ Kupffer Staurosporine datasheet cells. This may be due to higher TNF-α levels, the composition of cytokines, or the presence of an untested cytokine in the conditioned media. Moreover, it is possible that the kinetics of cytokine expression is as important as the composition of cytokines produced. TK−/− hepatocytes are protected compared to TK+/+ hepatocytes from TNF-α/ActD initiated cell death over the range of 0.5 to 5 ng/mL of TNF-α, which are similar to the serum TNF-α levels observed in the previously reported in vivo experiment.16

Whether the observed differences in hepatocyte viability are sufficient to explain the in vivo observations by Leonis et al.16 is not discernable by this assay. Hepatocytes plated ex vivo are without feedback mechanisms to Kupffer cells and other hepatic cell types and, thus, the magnitude of the effect of TNF-α ex vivo may not completely mimic what is observed in vivo. However, the results from the conditional deletion of Ron selectively in hepatocytes support the significance of our

Bortezomib in vitro ex vivo culture conditions and prior in vivo experiments. Previously, we demonstrated that the protected liver injury response to treatment with LPS/GalN in Ron TK−/− mice was associated with a 1- to 2-hour delay in the progression to death based on survival analyses.16 The lack of a more significant discrepancy in the time to mortality may be multifactorial and confounded by the sensitivity of the Ron TK−/− mice to LPS alone and by the severe necrosis and endothelial damage that is observed in the model. Despite the modest overall survival benefit of the TK−/− mice compared to controls, less liver injury was observed in the TK−/− mice as judged by liver histopathology, ALT levels, hepatocyte TUNEL staining, and the extent of hepatic apoptosis. Similar protected Alectinib phenotypes were observed in the Alb-Cre Ron TKfl/fl mice as the Ron

TK−/− mice compared to control mice. This is based on a reduction in liver histopathology and significantly decreased ALT levels and TUNEL staining in the Alb-Cre Ron TKfl/fl mice compared to controls. Interestingly, a 1- to 2-hour increase in survival time in the Alb-Cre Ron TKfl/fl mice was also observed compared to controls. Therefore, the data are consistent with a protected liver phenotype in the Alb-Cre Ron TKfl/fl mice compared to controls. Our data also show a significant decrease in survival of the LysCre mice and associated worsened liver phenotypes in these mice compared to Alb-Cre Ron TKfl/fl and wildtype mice and supports the premise that Ron functions in both cellular compartments in vivo. Our results show increased NF-κB activation in hepatocytes that lack Ron signaling.

We hypothesized that the call is specific to provisioning behavior in the context of parent–offspring communication, and tentatively designated it ‘provisioning call’. To test this hypothesis, we observed nesting females in the laboratory to determine if and when they emitted the call, and the response of nymphs. In every case, the call was clearly coordinated with female provisioning behaviors: females emitted the call only upon returning to their nests with a drupe. Moreover,

nymphs quickly gathered to the drupe while the female was calling. Because nymphs usually hide in crevices throughout the nest debris while the mother is foraging, we also hypothesized that the provisioning call functions to induce nymphs to gather and feed synchronously on newly provisioned drupes. A playback experiment indicated that significantly more nymphs gathered on a drupe with the playback call than without the this website call,

supporting this hypothesis. Furthermore, observations through nymphal development revealed that the total length of all sound bouts in a single provisioning Selleck LY294002 call was shorter for females with older nymphs. This is consistent with the assumption that older nymphs should gather on the provisioned drupe more quickly than young, less-motile nymphs. To the best of our knowledge, this is the first report of a parent producing sound and/or vibration signals directly to offspring at repeated progressive provisioning events in a subsocial insect. “
“Apex predators are essential for the viability of healthy ecosystems. By studying carnivoran feeding ecology, we can obtain a better understanding of the ecological limits, resilience and predator–prey dynamics that govern these populations. However, monitoring elusive predators – like the leopard Panthera pardus – is often fraught with logistical and financial constraints, particularly Montelukast Sodium in inaccessible terrain. In this study, we identified clusters of Global Positioning System (GPS) points

from four GPS-collared leopards and investigated them in the field for potential kills. Environmental data from cluster sites were gathered alongside spatial and temporal data collected via GPS cluster analysis to develop statistical models capable of predicting the occurrence of leopard predatory events. Our results demonstrate that leopard predation can be accurately modelled either by using a combination of field data (i.e. collected at cluster sites) and remote data (i.e. obtained via GPS analysis), or simply remote data alone. Kills were more likely to be present at clusters where leopards exhibited longer handling times, at sites with dense vegetation cover, when leopards were more active 12 h before the cluster than 12 h after, where more tree refugia were present, in areas of higher elevation, at sites containing low levels of shrub cover, and when clusters began during diurnal or crepuscular hours.

To calculate net benefits, the quality adjusted life year, that significantly reflects such health gain, has to be compared with specific economic impacts. Differences in data sources, in medical practice and/or in healthcare systems and costs, imply that most current pharmacoeconomic analyses are confined to a narrow healthcare payer perspective. Long-term/lifetime prospective or observational studies, devoted to a careful definition of when to start a treatment; of regimens (dose and type of product) to employ, and of inhibitor population (children/adults, low-responding/high responding inhibitors)

to study, are thus urgently needed to allow for newer insights, based on reliable data sources into resource allocation, effectiveness and cost-utility analysis in the treatment of haemophiliacs with inhibitors. selleck chemicals “
“Therapy with fresh frozen plasma (FFP) confers serious

risks, such as contraction of blood-borne viruses, allergic reaction, volume overload and development of alloantibodies. The aim of this study was to apply principles Afatinib supplier of pharmacokinetic (PK) modelling to individual factor content of FFP to optimize individualized dosing, while minimizing potential risks of therapy. We used PK modelling to successfully target individual factor replacement in an 8-month-old patient receiving FFP for treatment of a severe congenital factor V (FV) deficiency. The model fit for the FV activity vs. time data was excellent (r = 0.98) and the model accurately predicted FV activity during the intraoperative and postoperative period. Accurate PK modelling pheromone of individual factor activity in FFP has the potential to provide better targeted therapy, enabling clinicians to more precisely dose patients requiring coagulation products, while avoiding wasteful and expensive product overtreatment, minimizing potentially life-threatening complications due

to undertreatment and limiting harmful product-associated risks. “
“Summary.  All UK patients with bleeding disorders treated with any UK-sourced pooled factor concentrates between 1980 and 2001 have been informed that they may be at an increased risk of infection with variant Creutzfeldt–Jakob disease (vCJD). We describe a study to detect disease-associated, protease-resistant prion protein (PrPres) in 17 neurologically aysmptomatic patients with haemophilia considered to be at increased risk of vCJD. Materials from 11 autopsy and seven biopsy cases were analysed for PrPres. The tissues available from each case were variable, ranging from a single biopsy sample to a wide range of autopsy tissues. A single specimen from the spleen of one autopsy case gave a strong positive result on repeated testing for PrPres by Western blot analysis. This tissue came from a 73-year-old male patient with no history of neurological disease, who was heterozygous (methionine/valine) at codon 129 in the prion protein gene.

As for O-linked glycosylation, the presence of at least seven O-linked carbohydrate structures glycans in the FVIII B-domain has been reported [3,4]. Unfortunately, no information http://www.selleckchem.com/products/BKM-120.html on their location and precise structure is available, except for the detection of a single di-sialylated T-antigen at position Ser750 in a recombinant B-domainless FVIII preparation

[5]. Interestingly, comparison of pd-FVIII and rFVIII has revealed a number of subtle differences in their glycan structures. First, pd-FVIII but not rFVIII seems to carry blood-group determinants on its biantennary sugar chains [1]. Second, Hironaka et al. detected the presence of Gal(α1-3) Gal structures on rFVIII derived from BHK-cells but not on pd-FVIII. The incorporation of Gal(α1-3) Gal structures requires the presence of α1,3-galactosyltransferase, an enzyme that is mainly expressed in cells of non-primate CT99021 mw origin, the type of cells used for the production of current rFVIII products. Third, human cells differ from other mammalian cells in that they express a non-functional variant of cytidine monophosphate N-acetylneuraminic acid hydroxylase, which catalyses the conversion

of the sialic acid N-acetyl neuraminic acid (Neu5Ac) into N-Glycolylneuraminic acid (Neu5Gc) [6]. It is possible therefore that rFVIII contains both Neu5Ac and Neu5Gc, whereas pd-FVIII selectively carries the Neu5Ac sialic acid. Of note, the non-human nature of Gal(α1-3)Gal and Neu5Gc structures has been associated with the development of antibodies against these structures, and the presence of, for instance, the Gal(α1-3)Gal moiety on biotherapeutics can cause adverse events [6,7]. Whether these structures contribute to the immune response following treatment with rFVIII is unknown, but so far no evidence in support of this possibility has been provided. Intracellular

processing and routing of FVIII requires the interaction of this molecule with a number of glycan-binding chaperones, including calnexin, calreticulin and the LMAN1(ERGIC53)/MCFD2 complex (for a more detailed review see [8]). Calnexin and calreticulin are resident ER chaperone proteins that interact with mono-glucosylated carbohydrate structures that are present on proteins in the early stage of synthesis, and are part of the quality control system Quinapyramine of the cell. The interaction with both chaperones is necessary for optimal protein folding. Once properly folded, trimming of the terminal glucose residue results in dissociation of the protein from both chaperones, allowing the protein to be routed from the ER to the Golgi. With regard to FVIII, it has been shown that the glycans in the B-domain play an important role in the interaction with calreticulin/calnexin [9]. The transition from the ER to the Golgi involves the interaction between FVIII and the LMAN1 (ERGIC-53)/MCFD2 complex.

Each tumor was treated with a single electrode placement and just one ablation. Each patient was discussed in a multidisciplinary team meeting before the appropriate approach was decided. Operative mortality was defined as death within the same hospital admission after treatment. Mortality rates were compared over a 30-day period, between the two treatment groups. All adverse events, including the pain after treatment, were recorded and compared. Abdominal contrast-enhanced CT (SOMATOMAR-T CT scanner, Siemens AG, Germany) was conducted 1 month later, or magnetic resonance imaging

(MRI) (GE Signa HDx 1.5T MRI machine, Milwaukee, WI, USA) was used while patients were allergenic to the Omnipaque Solution (GE Healthcare, Shanghai, China). Patients routinely Decitabine received plain and triphasic RAD001 scans from 2 cm above right diaphragm to 2 cm below the inferior pole of the liver. Serum concentrations of α-fetoprotein (AFP) were measured on all the patients approximately 1 month after the treatment. Thereafter, all patients were regularly monitored for any intrahepatic recurrence or distant metastasis every 3 months in the first 2 years with measurement of serum AFP level, liver function tests, chest radiography, and CT or MRI scan. The outcome measures

were completed and conducted with complete treatment rate, post-RFA and surgery complications, treatment-related mortality, and disease-free and overall survival rates. Complete ablation was defined as the absence of any peripheral only enhancement in the contrast-enhanced phase 1 month after the RFA treatment. Local recurrence was defined as recurrences contiguous to or within resection or ablated areas. Distant intrahepatic recurrence was defined as a new tumor that appeared in the liver away from the ablated or operation area.

When intrahepatic recurrences were detected, they were treated with either transarterial chemoembolization (TACE), or repeat hepatectomy, or RFA, or liver transplantation after discussed in a multidisciplinary team meeting. Results were given as mean ± standard deviation. Clinical features and pathologic tumor-related factors were compared between the two groups using χ2 test or with Fisher’s exact test. The t-test was used for continuous variables in a parametric fashion, whereas the Mann–Whitney U-test was used for non-parametric data. The Kaplan–Meier method was used to estimate the cumulative incidences of events, and differences in these incidences were evaluated using the log–rank test. All statistical evaluations were performed using the SPSS 21.0 software package (SPSS Inc., Chicago, IL, USA). All statistical tests were two-sided, and a significant difference was considered when P < 0.050.