Startseite Medizin Effects of hydroxyethyl starch and gelatin on the risk of acute kidney injury following orthotopic liver transplantation: A multicenter retrospective comparative clinical study
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Effects of hydroxyethyl starch and gelatin on the risk of acute kidney injury following orthotopic liver transplantation: A multicenter retrospective comparative clinical study

  • Yingqi Chen , Xinyu Ning , Haiyang Lu , Sainan Zhu , Anshi Wu , Jia Jiang , Shanshan Mu , Jing Wang , Xu Niu , Shengnan Li , Lingdi Hou , Yanxing Zhao , Wenfei Lv , Meixia Shang , Chen Yao , Shujun Han EMAIL logo , Ping Chi EMAIL logo , Fushan Xue EMAIL logo und Yun Yue EMAIL logo
Veröffentlicht/Copyright: 23. Februar 2021
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Aus der Zeitschrift Open Medicine Band 16 Heft 1

Abstract

Objectives

This multicenter retrospective study aimed to compare the effects of HES and gelatin (GEL) on the risk of post-OLT AKI.

Method

A total of 1,672 patients undergoing OLT were enrolled from major transplant centers in China between 2005 and 2013. These patients were divided into three groups: GEL, hydroxyethyl starch (HES), and GEL + HES group.

Results

There was no significant difference in the incidence of post-OLT AKI among the GEL, HES, and GEL + HES groups. The GEL + HES group had a lower incidence of stage II post-OLT AKI than the other two groups. Compared with patients receiving GEL, patients receiving HES did not harbor an increased risk of AKI. Our results showed that MELD score (adjusted odds ratio [OR], 1.579; 95% confidence interval [CI], 1.123–2.219; P = 0.009) and preoperative anemia (adjusted OR, 1.533; 95% CI, 1.212–1.939; P < 0.001) were independent risk factors for post-OLT AKI, and normal preoperative Scr level (vs abnormal; adjusted OR, 0.402; 95% CI, 0.222–0.729; P = 0.003) was independent protective factors for post-OLT AKI.

Conclusion

This large-scale multicenter retrospective study found that the intraoperative use of HES did not increase the overall incidence of post-OLT AKI in patients when compared with GEL, and whether to increase the risk of post-OLT AKI needs to be further explored.

Keywords: hydroxyethyl starch; gelatin; acute kidney injury; liver transplantation; risk factors

1 Introduction

Hydroxyethyl starch (HES) is a plasma substitute widely used for intravascular volume supplement or resuscitation during transplant surgeries [1,2,3,4]. Several large-scale randomized controlled trials indicated that HES might impair kidney functions and increase the risk of acute kidney injury (AKI) in critically ill patients [5,6,7]. Intravenous human albumin and synthetic colloids are usually mandatory in patients undergoing orthotopic liver transplant (OLT) due to preoperative hypoalbuminemia and low colloid osmotic pressure [8,9]. In China, a combination of albumin and synthetic colloids (HES and/or gelatin [GEL]) has been widely used during OLT [10,11]. In addition, AKI is a common postoperative complication of OLT, and its incidence was reported to be more than 50% in post-OLT patients; AKI is associated with prolonged hospitalization and poor prognosis [12,13].

The etiology of post-OLT AKI is multifactorial [14], and the definitive mechanism regarding the potential nephrotoxicity of HES has not been well elucidated [15]. Foremost, the effects of HES on the risk of AKI remain controversial. A report from a large database including 44,176 adult patients undergoing noncardiac surgery showed that HES had dose-dependent nephrotoxicity with an odds ratio of 1.21 (95% CI, 1.06–1.38) for the development of postoperative AKI [16]. Some scholars proposed that, with the continuous upgrading of HES, its potential damage to renal function and coagulation function has been significantly reduced [17,18]. The CRISTAL randomized trial demonstrated that the use of colloids vs crystalloids does not result in significant differences in 28-day mortality and the need for renal replacement therapy in critically ill patients with hypovolemia [19]. A recent systematic review and meta-analysis of randomized controlled trials also indicated that HES, compared with crystalloid or other colloidal solutions, may not increase the risk of renal dysfunction in postoperative patients [20]. In post-OLT patients, a small-sample prospective, randomized, controlled clinical trial showed that the intraoperative use of HES as an alternative to human albumin resulted in the equivalent renal outcomes [8]. However, another retrospective clinical study found that the intraoperative use of HES significantly increased the risk of post-OLT AKI when compared with albumin, with an odds ratio of 2.94 (95% CI, 1.13–7.7) [11]. To the best of our knowledge, there has been no large-sample, multicenter clinical study evaluating the nephrotoxicity of HES. This study was aimed to compare the effects of HES and GEL on the risk of AKI after OLT.

2 Materials and methods

2.1 Patients

This multicenter retrospective study has been registered at the Chinese Clinical Trial Register (http://www.chictr.org.cn; identifier: ChiCTR-TRC-14004211). This study was approved by the Institutional Review Board of Beijing Chaoyang Hospital (No. 2013-159). A total of 1,672 patients undergoing OLT were enrolled from three major transplant centers in China (Beijing Chaoyang Hospital, Chinese People’s Liberation Army General Hospital, and Beijing You’An Hospital) between 2005 and 2013. The medical records of these patients were collected and analyzed.

Inclusion criterion was as follows: patients receiving OLT.

Exclusion criteria were as follows: (1) <14 years of age, (2) simultaneous dual-organ (liver and kidney) transplant, (3) no administration of intraoperative GEL or HES, or (4) and incomplete perioperative data.

Eventually, 167 patients were excluded, and 1,505 patients were included for the subsequent analyses (Figure 1). According to the types of synthetic colloids used during the OLT surgery, these patients were divided into three groups: GEL group, HES group, and GEL + HES group. Furthermore, we assessed the effects of HES exposure on the risk of post-OLT AKI; based on the volume of HES used, patients were classified into three groups: no HES exposure, low (≤1,500 mL) HES exposure, and high (>1,500 mL) HES exposure.

Figure 1 Enrollment flowchart.
Figure 1

Enrollment flowchart.

  1. Ethics approval and consent to participate: This study has been registered at Chinese Clinical Trial Register (http://www.chictr.org.cn; Identifier: ChiCTR-TRC-14004211. Registered on 26 January 2014). The study has obtained approval from the Ethical Committee (No. 2013-159). Informed consent of patients was waived because this study was retrospective.

2.2 Evaluation of post-OLT AKI

The individual kidney function was evaluated within 7 days after OLT. AKI, determined based on the postoperative serum creatinine (Scr) level, was diagnosed according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria [21,22]: (1) stage I, an increase in the Scr level of ≥26 μmol/L within 48 h or an Scr level of 1.50–1.99 times the baseline level within 7 days; (2) stage II, an Scr level of 2.00–2.99 times the baseline level within 7 days; and (3) stage III, an Scr level of ≥354 μmol/L or an Scr level of >3.0 times the baseline level within 7 days or the initiation of renal replacement therapy (RRT; including hemodialysis and hemofiltration). The baseline Scr level was measured on admission. In addition, the 28-day mortality and severe cases treated with RRT were analyzed.

2.3 Statistical analysis

The EpiData software (version 3.0, www.epidata.dk) was used for data management, and the SAS software (version 9.4, SAS Institute, Cary, North Carolina) was used for statistical analyses. Measurement variables with normal distribution were presented as means ± standard deviation (SD); nonnormal variables were presented as median (interquartile range [IQR]). Student t-test or Wilcoxon rank-sum test was used for two-group comparisons. One-way analysis of variance or Kruskal–Wallis test was used for three-group comparisons. Categorical variables were presented as frequency and percentage, and they were compared using the Chi-square test. The ranked variables were presented as frequency and percentage and compared using the Wilcoxon rank-sum test or Kruskal–Wallis test. The paired t-test or Wilcoxon paired signed-rank test was used for intragroup comparisons.

Multivariate logistic regression models were used for identifying the potential risk factors of AKI. In model 1, the candidate factors included age, gender, hemoglobin, anemia, hypoalbuminemia, inotropic agents, surgical types, the Scr level, model for end-stage liver disease (MELD) score, duration of anhepatic phase, and the use of colloids (GEL, HES, or GEL + HES). In model 2, besides the aforementioned factors, the HES exposure was also included for the analysis. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in the two models. Two-tailed P < 0.05 was considered statistically significant.

3 Results

3.1 Clinical characteristics

There were 736 patients in the GEL group, 586 patients in the HES group, and 183 patients in the GEL + HES group. The detailed clinical characteristics were summarized in Table 1. There were no significant differences in gender or age among the three groups. The GEL + HES group has the highest hemoglobin level (112.0 ± 27.3 g/L) and preoperative Scr level [69.5 (57.9, 84.5) μmol/L] and the lowest MELD score (10.9 ± 8.4) than the GEL and HES groups (hemoglobin level, P < 0.001; preoperative Scr level, P = 0.041; MELD score, P < 0.001). In the GEL group, 603 (82.0%) patients underwent classic OLT and 133 (18.0%) patients underwent piggyback OLT; in the HES group, 350 (59.7%) patients underwent classic OLT and 236 (40.3%) patients underwent piggyback OLT; and in the GEL + HES group, 96 (52.5%) patients underwent classic OLT and 87 (47.5%) patients underwent piggyback OLT. The GEL group had the highest proportion of patients with vasopressin use (80.2%) and patients with diuretic use (77.2%) than other groups (vasopressin use, P = 0.007; diuretic use, P < 0.001). There was no significant difference in immunosuppressant use (P = 0.825) or surgery duration (P = 0.447) among the three groups. The anhepatic phase was longest in the GEL + HES group (P < 0.001).

Table 1

Clinical characteristics of enrolled subjects

Characteristics GEL group (n = 736) HES group (n = 586) GEL + HES group (n = 183) P value
Male, n (%) 606 (82.3) 470 (80.2) 158 (86.3) 0.160
Age (years) 49.4 ± 9.6 49.2 ± 10.2 49.0 ± 8.9 0.924
Hemoglobin (g/L) 104.2 ± 24.0 103.2 ± 24.2 112.0 ± 27.3 <0.001
Preoperative Scr (μmol/L) 65.0 [53.0, 82.0] 65.0 [53.0, 79.6] 69.5 [57.9, 84.5] 0.041
MELD score 13.8 ± 9.3 12.0 ± 9.6 10.9 ± 8.4 <0.001
Type of OLT, n (%)
Classic 603 (82.0) 350 (59.7) 96 (52.5) <0.001
Piggyback 133 (18.0) 236 (40.3) 87 (47.5)
Vasopressin use, n (%) 590 (80.2) 439 (74.9) 129 (70.5) 0.007
Diuretic use, n (%) 568 (77.2) 352 (60.1) 81 (44.3) <0.001
Immunosuppressant use, n (%) 674 (91.6) 533 (91.0) 169 (92.3) 0.825
Surgery duration (hours) 10.1 ± 2.4 10.1 ± 2.7 10.2 ± 2.3 0.477
Anhepatic phase (minutes) 67.8 ± 27.3 75.6 ± 28.9 84.0 ± 34.7 <0.001

Abbreviations: GEL, gelatin; HES, hydroxyethyl starch; Scr, serum creatinine; OLT, orthotopic liver transplantation; MELD, model for end-stage liver disease.

3.2 Impacts of HES on postoperative renal function and outcomes

The comparisons between postoperative Scr levels and preoperative baseline levels are shown in Figure 2. On day 1 postoperatively, the Scr levels were significantly increased in all groups when compared with the baseline levels (P < 0.001), and the increase of Scr levels was most remarkable in the GEL group (P < 0.001). On day 3 and day 7 postoperatively, the Scr levels were significantly decreased than those on day 1 postoperatively (P < 0.001). On postoperative day 7, the Scr levels were lower than the baseline levels in the HES and GEL + HES groups (P < 0.001), and they were higher than the baseline levels in the GEL group (P < 0.001).

Figure 2 Comparisons of intraoperative and postoperative Scr levels (μmol/L) with the preoperative baseline levels. POD: postoperative day; * P < 0.001, # P < 0.05, compared with the preoperative baseline levels.
Figure 2

Comparisons of intraoperative and postoperative Scr levels (μmol/L) with the preoperative baseline levels. POD: postoperative day; * P < 0.001, # P < 0.05, compared with the preoperative baseline levels.

The overall incidence of post-OLT AKI was 46.5% in the GEL group, 41.5% in the HES group, and 40.4% in the GEL + HES group (Figure 3). There was no significant difference in the overall incidence of post-OLT AKI among the three groups (P = 0.119). The incidences of stages I, II, and III AKI were 26.9, 9.8, and 13.3% in the GEL group, respectively; 23.0, 10.8, and 11.6% in the HES group, respectively; and 23.5, 4.4, and 16.4% in the GEL + HES group, respectively. The GEL + HES group had a lower incidence of stage II post-OLT AKI than the other two groups (P = 0.035). There were no significant differences in the postoperative 28-day mortality (P = 0.538) or administration of RRT among the three groups (P = 0.417).

Figure 3 Incidence and stages of post-OLT AKI in different groups.
Figure 3

Incidence and stages of post-OLT AKI in different groups.

The overall incidence of post-OLT AKI in patients with no HES exposure, low HES exposure, and high HES exposure was 47.6, 42.3, and 40.4%, respectively (Figure 4). There was no significant difference in the HES exposure between patients with AKI and patients without AKI (P = 0.070). The postoperative data are summarized in Table 2.

Figure 4 Incidence and stages of post-OLT AKI in patients with different HES exposures.
Figure 4

Incidence and stages of post-OLT AKI in patients with different HES exposures.

Table 2

Postoperative outcomes

Outcome parameters GEL group (n = 736) HES group (n = 586) GEL + HES group (n = 183) P value
Scr (μmol/L)
Postoperative day 1 82.0 [62.0, 112.3] 76.5 [60.0, 105.0] 84.9 [66.1, 114.0] 0.007
Postoperative day 3 73.0 [57.0, 103.0] 68.8 [55.0, 94.0] 77.0 [57.0, 97.7] 0.027
Postoperative day 7 67.0 [55.0, 88.0] 63.0 [52.0, 84.0] 66.0 [57.2, 85.0] 0.008
Recovery time (hours) 7.3 [5.0, 12.0] 7.0 [4.5, 11.0] 8.0 [5.3, 22.5] 0.008
Ventilation time (hours) 10.5 [7.5, 16.2] 14.0 [8.7, 30] 12.8 [9.3, 29.5] <0.001
Fluid input (mL)
Postoperative day 1 3494.7 ± 1539.72 3628.1 ± 1673.3 3481.6 ± 1626.7 0.318
Postoperative day 3 3325.9 ± 1428.0 3665.1 ± 1619.2 3134.1 ± 1222.8 <0.001
Postoperative day 7 2786.2 ± 1625.1 3096.1 ± 1737.2 2486.6 ± 1238.4 <0.001
Urine output (mL)
Postoperative day 1 2577.2 ± 1222.8 2367.9 ± 1132.3 2324.9 ± 1062.9 <0.001
Postoperative day 3 2632.9 ± 1190.0 2847.5 ± 1214.8 2615.8 ± 951.1 <0.001
Postoperative day 7 2442.1 ± 1080.8 2643.5 ± 1216.8 2533.0 ± 1040.6 0.006
AKI, n (%)
Total 342 (46.5) 243 (41.5) 74 (40.4) 0.119
Stage I 198 (26.9) 135 (23.0) 43 (23.5) 0.241
Stage II 72 (9.8) 63 (10.8) 8 (4.4) 0.035
Stage III 98 (13.3) 68 (11.6) 30 (16.4) 0.231
28-day mortality, n (%) 26 (3.5) 16 (2.7) 4 (2.2) 0.538
RRT, n (%) 39 (5.3) 38 (6.5) 14 (7.7) 0.417
Hemodialysis 7 (1.0%) 8 (1.4%) 2 (1.1%) 0.777
Hemofiltration 32 (4.3%) 30 (5.1%) 12 (6.6%) 0.446
MELD score 13.76 ± 9.28 11.97 ± 9.60 10.87 ± 8.38 <0.001
MELD group
Low score group (<30), n (%) 684 (86.80) 571 (90.78) 181 (91.88) 0.023
High score group (≥30), n (%) 104 (13.20) 58 (9.22) 16 (8.12)
Time of anhepatic phase
≤60 min, n (%) 458 (57.76) 269 (42.30) 64 (31.84) <0.001
>60 min, n (%) 335 (42.24) 367 (57.70) 137 (68.16)

Abbreviations: GEL, gelatin; HES, hydroxyethyl starch; Scr, serum creatinine; AKI, acute kidney injury; RRT, renal replacement treatment.

Meanwhile, we also evaluated MELD score to study the renal function more comprehensively. The numbers of post-OLT AKI patients were 788 in the GEL group, 629 in the HES group, and 197 in the GEL + HES group (P < 0.001). The mean values of the MELD score were 13.76 ± 9.28 in the GEL group, 11.97 ± 9.60 in the HES group, and 10.87 ± 8.38 in the GEL + HES group. The MELD scores were divided into high and low groups by 30 points. The incidence of the low-score groups was 86.80% in the GEL group, 90.78% in the HES group, and 91.88% in the GEL + HES group (P = 0.023). As for the duration of the anhepatic phase, the incidence of the part ≤60 min was 57.76% in the GEL group, 42.30% in the HES group, and 31.84% in the GEL + HES group (P < 0.001).

3.3 Risk factors for post-OLT AKI

A total of 671 (44.6%) patients developed post-OLT AKI, and univariate regression analysis showed that the preoperative Scr level, hemoglobin level, MELD score, and hypoalbuminemia might be potential risk factors of post-OLT AKI (P < 0.05). However, age, gender, types of OLT, use of vasopressin, duration of anhepatic phase, type of colloidal solution, and dosage of intraoperative HES were not significantly associated with the occurrence of post-OLT AKI (P > 0.05). The detailed data are summarized in Table 3.

Table 3

Univariate analysis for risk factors of post-OLT AKI

Variables Non-AKI (n = 834) AKI (n = 671) P value
Age (years) 49.3 ± 9.6 49.2 ± 9.9 0.829
Gender
Male, n (%) 691 (82.9) 543 (80.9) 0.333
Female, n (%) 143 (17.1) 128 (19.1)
Preoperative Scr level (μmol/L)
Normal, n (%) 817 (98.0) 638 (95.1) 0.002
Abnormal, n (%) 17 (2.0) 33 (4.9)
Hemoglobin (g/L) 107.1 ± 24.9 101.9 ± 24.2 <0.001
MELD score
<25, n (%) 763 (91.5) 577 (86.0) 0.001
≥25, n (%) 71 (8.5) 94 (14.0)
Hypoalbuminemia
Present, n (%) 560 (67.2) 415 (61.9) 0.032
Absent, n (%) 274 (32.8) 256 (38.1)
Types of OLT
Classic, n (%) 589 (70.6) 460 (68.6) 0.385
Piggyback, n (%) 245 (29.4) 211 (31.4)
Vasopressin
Use, n (%) 635 (76.1) 523 (77.9) 0.409
None, n (%) 199 (23.9) 148 (22.1)
Anhepatic phase
≤60 min, n (%) 419 (50.2) 332 (49.5) 0.769
>60 min, n (%) 415 (49.8) 339 (50.5)
Type of colloidal solution
GEL, n (%) 386 (46.3) 350 (52.2)
HES, n (%) 339 (40.7) 247 (36.8) 0.070
GEL + HES, n (%) 109 (13.1) 74 (11.0)
HES dosage, n (%)
None 386 (46.3) 350 (52.2)
≤1,500 mL 339 (40.7) 247 (36.8) 0.070
>1,500 mL 109 (13.0) 74 (11.0)

Abbreviations: AKI, acute kidney injury; Scr, serum creatinine; MELD, model for end-stage liver disease; OLT, orthotopic liver transplantation; GEL, gelatin; HES, hydroxyethyl starch.

Further multivariate logistic regression analysis showed that MELD score (adjusted odds ratio [OR], 1.579; 95% confidence interval [CI], 1.123–2.219; P = 0.009) and preoperative anemia (adjusted OR, 1.533; 95% CI, 1.212–1.939; P < 0.001) were independent risk factors for post-OLT AKI, and normal preoperative Scr level (vs abnormal; adjusted OR, 0.402; 95% CI, 0.222–0.729; P = 0.003) was independent protective factors for post-OLT AKI. The detailed statistical results are summarized in Table 4.

Table 4

Multivariate logistic regression analysis for risk factors of post-OLT AKI

Covariates Adjusted OR 95% CI P value
MELD score (high vs low) 1.579 1.123–2.219 0.009
Anemia (with vs without) 1.533 1.212–1.939 <0.001
Hypoalbuminemia (with vs without) 1.130 0.903–1.414 0.286
Preoperative Scr level (normal vs abnormal) 0.402 0.222–0.729 0.003

Abbreviations: AKI, acute kidney injury; OR, odds ratio; 95% CI, 95% confidence interval; MELD, model for end-stage liver disease; OLT, orthotopic liver transplantation.

4 Discussion

In clinical practice, synthetic colloidal solutions have been commonly used as plasma substitutes for intravascular volume supplement or volume resuscitation during OLT [23]. Given that HES may be a potential risk factor for postoperative AKI, this large-scale multicenter retrospective study evaluated the effects of intraoperative HES use on the renal function within 7 days after OLT. Although the AKIN (Acute Kidney Injury Network) classification, the RIFLE (risk, injury, failure, loss of kidney function, and end-stage renal failure) classification, and the KDIGO classification are the AKI diagnosis criteria commonly used in the clinical practice [24,25,26], we used the Scr criteria of KDIGO classification to determine the post-OLT AKI in the current study as the Scr level was a sensitive index for the early diagnosis of renal damage [27].

The overall incidence of post-OLT AKI in our study was as high as 43.7%, which is consistent with the previous literature [12,13]. However, our results showed that there was no significant difference in the incidence of post-OLT AKI among the three groups. In addition, no significant intergroup difference was noted in the 28-day mortality or the postoperative administration of RRT. Furthermore, compared with patients receiving GEL, patients receiving HES did not show any increased risk for the post-OLT AKI. Compared to patients with no HES exposure, the adjusted odds ratio for the post-OLT AKI was 0.748 (95% CI, 0.599–0.933; P = 0.010) in patients with low HES exposure and 1.113 (95% CI, 0.696–1.779; P = 0.654) in patients with high HES exposure. These results indicate that intraoperative HES use does not result in an increased risk of post-OLT AKI when compared with GEL.

Patients receiving GEL were enrolled as controls as the average molecular weight of 4% GEL is low (30 kDa), and thus, GEL can be rapidly excreted through the kidney [28]. Due to the short half-life of GEL in the blood vessel and its rapid excretion, GEL has been shown to improve the renal function in the early stage of hemorrhagic shock [29,30]. Furthermore, a meta-analysis showed that the use of a GEL solution as a plasma substitute for perioperative and critically ill patients was associated with a lower risk of acute renal failure when compared to old HES solutions with a high molecular weight [31].

The definitive mechanisms of renal toxicity caused by HES remain unknown. We speculate that the nephrotoxicity may be associated with the extravasation and deposition of HES in tissues. Osmotic nephrosis is morphologically characterized by tubular swelling due to cytoplasmic vacuole formation, and it is considered as one of the causes of renal toxicity induced by HES [32,33]. In addition, HES solutions may damage the kidney by reducing osmotic pressure [32]. With a lower degradability in the interstitial space and the reticuloendothelial system, old HES solutions with high molecular weight are inclined to accumulate, which probably contributes to the renal toxicity as well [28,33]. However, the current study provided new evidence for the kidney safety of intraoperative HES use in OLT cases.

The reasons for our results that intraoperative HES use did not increase the risk of post-OLT AKI may be multifactorial. First, OLT patients usually have a low colloid osmotic pressure due to hypoalbuminemia, and thus, the volume expansion therapy may be beneficial. In addition, the low colloid osmotic pressure may decrease the occurrence of HES extravasation. Second, the HES solution used in this study is the third generation of HES, with an average molecular weight of approximately 130 kDa and a molar substitution of approximately 0.4. The plasma clearance of HES 130/0.4 is 20-fold greater than that of old HES 450/0.7, and thus, the toxic effects of tissue deposition are lower for HES 130/0.4 [34]. Third, the volume of intraoperative HES use may be an important factor affecting the occurrence of postoperative AKT. Brunkhorst et al. found that the volume of HES was associated with the risk of AKI in a dose-effect manner [7]. A retrospective study conducted by Kashy et al. in patients with noncardiac surgery also showed that HES had dose-dependent renal toxicity [16]. Moreover, Hand et al. demonstrated that the incidence of postoperative AKI was higher in the large-volume HES group than that in the small-volume HES and albumin groups [11]. Generally, the recommended dosage of HES in clinical practice is 33 mL/kg [35], and the dosage of new-generation HES 130/0.4 is recommended as a daily maximum of 50 mL/kg [36]. In our study, the mean intraoperative dosage was only 1.7 ± 1.2 mL/kg/h in the HES group and 1.5 ± 0.9 mL/kg/h in the GEL + HES group, and the total intraoperative dosage of HES was less than 33 mL/kg. Therefore, we found that the incidence of post-OLT AKI was not significantly correlated with the HES use, which may be attributed to the relatively small dosage of HES. Fourth, the rapid recovery of liver function after OLT helps maintain hemodynamic stability and renal functions. However, septic and critically ill patients often suffer from multiple organ dysfunctions, and a relatively high dosage of HES is administrated over a prolonged period, which may increase the risk of AKI [37].

We also searched relevant studies in PubMed, EMBASE, Cochrane Library, Ovid, and a major Chinese database (CNKI). Key terms included “liver transplantation,” “hydroxyethyl starch,” “colloid,” “kidney injury,” and “renal function.” Six retrospective studies and two randomized clinical trials were retrieved, and they concluded that HES did not cause any significant postoperative renal dysfunction [10,11,23,38,39,40]. However, one of these studies showed a higher risk of AKI in patients receiving HES 130/0.4 > 30 mL/kg [39]; another study compared the effects of albumin with old HES (Hextend) on the renal outcomes after OLT and showed no significant difference in the renal function during the postoperative 30 days and 6 months, while a higher dosage of Hextend was significantly associated with worse postoperative renal function [40]. Hand et al. proposed that that intraoperative HES (130/0.4) use was associated with an increased risk of postoperative AKI in post-OLT patients when compared with albumin, which may be due to the dose-dependent renal toxicity of HES [11]. A small-scale randomized controlled trial showed that the use of HES 130/0.4 during and after OLT did not result in adverse effects on the renal function within 4 days postoperatively, while the authors also reminded prudently that their results could not be extended to patients with more severe preoperative renal injury [8]. The other randomized controlled trial performed in post-OLT patients with normal renal function found that neither GEL nor HES would cause any renal dysfunction requiring RRT, while GEL might have more remarkable renal toxicity [41].

Noteworthily, all of the aforementioned studies were small and single center. The strengths of this study are as follows: (1) a large sample size from three medical centers enhances the validity and generalizability of the results; (2) multivariable logistic regression analysis was used for controlling the potential effects of confounding variables. However, there are some limitations to the current study. First, this is a retrospective study that cannot exclude the admission bias; nevertheless, retrospective studies also have merits in the assessment of therapeutic safety as these studies have a large sample size and involve real-world patients. Second, intraoperative hemodynamic data were unavailable, which could not be included as covariates. Third, there were not enough cases for analyzing the necessity of the RRT treatment. Fourth, our grouping criteria for volumes of intraoperative HES use (none, <1,500 and >1,500 mL) are somewhat arbitrary. Finally, the incidence of post-OLT AKI during a 7-day postoperative period was evaluated, while the potential postoperative AKI-related complications were not fully investigated. In the future study, more large-scale, multicenter, randomized, and controlled clinical trials are warranted.

5 Conclusions

This large-scale multicenter retrospective study found that the intraoperative use of HES did not increase the overall incidence of post-OLT AKI in patients when compared with GEL, and whether to increase the risk of post-OLT AKI needs to be further explored. In addition, randomized controlled trials with large samples are warranted to further assess the kidney safety of HES in OLT patients.

Abbreviations

HES

hydroxyethyl starch

AKI

acute kidney injury

OLT

orthotopic liver transplant

GEL

gelatin

Scr

serum creatinine

KDIGO

kidney disease improving global outcomes

RRT

renal replacement therapy

SD

standard deviation

IQR

interquartile range

OR

odds ratio

CI

confidence interval

HB

hemoglobin

MELD

model for end-stage liver disease

Yingqi Chen, Xinyu Ning, Haiyang Lu, and Sainan Zhu contributed equally to this work.

tel: +86-137-0127-5595, fax: +86-10-8523-1699

  1. Funding: The authors received no specific funding for this work.

  2. Availability of data and materials: Y. Y, F. X, P. C., and S. H. had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

  3. Conflict of interest: The authors have no conflicts of interest to disclose.

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Received: 2020-05-10
Revised: 2020-11-17
Accepted: 2021-01-15
Published Online: 2021-02-23

© 2021 Yingqi Chen et al., published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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  213. Computer-assisted preoperative planning of reduction of and osteosynthesis of scapular fracture: A case report
  214. High quality of 58-month life in lung cancer patient with brain metastases sequentially treated with gefitinib and osimertinib
  215. Rapid response of locally advanced oral squamous cell carcinoma to apatinib: A case report
  216. Retrieval of intrarenal coiled and ruptured guidewire by retrograde intrarenal surgery: A case report and literature review
  217. Usage of intermingled skin allografts and autografts in a senior patient with major burn injury
  218. Retraction
  219. Retraction on “Dihydromyricetin attenuates inflammation through TLR4/NF-kappa B pathway”
  220. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part I
  221. An artificial immune system with bootstrap sampling for the diagnosis of recurrent endometrial cancers
  222. Breast cancer recurrence prediction with ensemble methods and cost-sensitive learning
https://doi.org/10.1515/med-2020-0183
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hydroxyethyl starch; gelatin; acute kidney injury; liver transplantation; risk factors
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Artikel in diesem Heft

  1. Research Articles
  2. Identification of ZG16B as a prognostic biomarker in breast cancer
  3. Behçet’s disease with latent Mycobacterium tuberculosis infection
  4. Erratum
  5. Erratum to “Suffering from Cerebral Small Vessel Disease with and without Metabolic Syndrome”
  6. Research Articles
  7. GPR37 promotes the malignancy of lung adenocarcinoma via TGF-β/Smad pathway
  8. Expression and role of ABIN1 in sepsis: In vitro and in vivo studies
  9. Additional baricitinib loading dose improves clinical outcome in COVID-19
  10. The co-treatment of rosuvastatin with dapagliflozin synergistically inhibited apoptosis via activating the PI3K/AKt/mTOR signaling pathway in myocardial ischemia/reperfusion injury rats
  11. SLC12A8 plays a key role in bladder cancer progression and EMT
  12. LncRNA ATXN8OS enhances tamoxifen resistance in breast cancer
  13. Case Report
  14. Serratia marcescens as a cause of unfavorable outcome in the twin pregnancy
  15. Spleno-adrenal fusion mimicking an adrenal metastasis of a renal cell carcinoma: A case report and embryological background
  16. Research Articles
  17. TRIM25 contributes to the malignancy of acute myeloid leukemia and is negatively regulated by microRNA-137
  18. CircRNA circ_0004370 promotes cell proliferation, migration, and invasion and inhibits cell apoptosis of esophageal cancer via miR-1301-3p/COL1A1 axis
  19. LncRNA XIST regulates atherosclerosis progression in ox-LDL-induced HUVECs
  20. Potential role of IFN-γ and IL-5 in sepsis prediction of preterm neonates
  21. Rapid Communication
  22. COVID-19 vaccine: Call for employees in international transportation industries and international travelers as the first priority in global distribution
  23. Case Report
  24. Rare squamous cell carcinoma of the kidney with concurrent xanthogranulomatous pyelonephritis: A case report and review of the literature
  25. An infertile female delivered a baby after removal of primary renal carcinoid tumor
  26. Research Articles
  27. Hypertension, BMI, and cardiovascular and cerebrovascular diseases
  28. Case Report
  29. Coexistence of bilateral macular edema and pale optic disc in the patient with Cohen syndrome
  30. Research Articles
  31. Correlation between kinematic sagittal parameters of the cervical lordosis or head posture and disc degeneration in patients with posterior neck pain
  32. Review Articles
  33. Hepatoid adenocarcinoma of the lung: An analysis of the Surveillance, Epidemiology, and End Results (SEER) database
  34. Research Articles
  35. Thermography in the diagnosis of carpal tunnel syndrome
  36. Pemetrexed-based first-line chemotherapy had particularly prominent objective response rate for advanced NSCLC: A network meta-analysis
  37. Comparison of single and double autologous stem cell transplantation in multiple myeloma patients
  38. The influence of smoking in minimally invasive spinal fusion surgery
  39. Impact of body mass index on left atrial dimension in HOCM patients
  40. Expression and clinical significance of CMTM1 in hepatocellular carcinoma
  41. miR-142-5p promotes cervical cancer progression by targeting LMX1A through Wnt/β-catenin pathway
  42. Comparison of multiple flatfoot indicators in 5–8-year-old children
  43. Early MRI imaging and follow-up study in cerebral amyloid angiopathy
  44. Intestinal fatty acid-binding protein as a biomarker for the diagnosis of strangulated intestinal obstruction: A meta-analysis
  45. miR-128-3p inhibits apoptosis and inflammation in LPS-induced sepsis by targeting TGFBR2
  46. Dynamic perfusion CT – A promising tool to diagnose pancreatic ductal adenocarcinoma
  47. Biomechanical evaluation of self-cinching stitch techniques in rotator cuff repair: The single-loop and double-loop knot stitches
  48. Review Articles
  49. The ambiguous role of mannose-binding lectin (MBL) in human immunity
  50. Case Report
  51. Membranous nephropathy with pulmonary cryptococcosis with improved 1-year follow-up results: A case report
  52. Fertility problems in males carrying an inversion of chromosome 10
  53. Acute myeloid leukemia with leukemic pleural effusion and high levels of pleural adenosine deaminase: A case report and review of literature
  54. Metastatic renal Ewing’s sarcoma in adult woman: Case report and review of the literature
  55. Burkitt-like lymphoma with 11q aberration in a patient with AIDS and a patient without AIDS: Two cases reports and literature review
  56. Skull hemophilia pseudotumor: A case report
  57. Judicious use of low-dosage corticosteroids for non-severe COVID-19: A case report
  58. Adult-onset citrullinaemia type II with liver cirrhosis: A rare cause of hyperammonaemia
  59. Clinicopathologic features of Good’s syndrome: Two cases and literature review
  60. Fatal immune-related hepatitis with intrahepatic cholestasis and pneumonia associated with camrelizumab: A case report and literature review
  61. Research Articles
  62. Effects of hydroxyethyl starch and gelatin on the risk of acute kidney injury following orthotopic liver transplantation: A multicenter retrospective comparative clinical study
  63. Significance of nucleic acid positive anal swab in COVID-19 patients
  64. circAPLP2 promotes colorectal cancer progression by upregulating HELLS by targeting miR-335-5p
  65. Ratios between circulating myeloid cells and lymphocytes are associated with mortality in severe COVID-19 patients
  66. Risk factors of left atrial appendage thrombus in patients with non-valvular atrial fibrillation
  67. Clinical features of hypertensive patients with COVID-19 compared with a normotensive group: Single-center experience in China
  68. Surgical myocardial revascularization outcomes in Kawasaki disease: systematic review and meta-analysis
  69. Decreased chromobox homologue 7 expression is associated with epithelial–mesenchymal transition and poor prognosis in cervical cancer
  70. FGF16 regulated by miR-520b enhances the cell proliferation of lung cancer
  71. Platelet-rich fibrin: Basics of biological actions and protocol modifications
  72. Accurate diagnosis of prostate cancer using logistic regression
  73. miR-377 inhibition enhances the survival of trophoblast cells via upregulation of FNDC5 in gestational diabetes mellitus
  74. Prognostic significance of TRIM28 expression in patients with breast carcinoma
  75. Integrative bioinformatics analysis of KPNA2 in six major human cancers
  76. Exosomal-mediated transfer of OIP5-AS1 enhanced cell chemoresistance to trastuzumab in breast cancer via up-regulating HMGB3 by sponging miR-381-3p
  77. A four-lncRNA signature for predicting prognosis of recurrence patients with gastric cancer
  78. Knockdown of circ_0003204 alleviates oxidative low-density lipoprotein-induced human umbilical vein endothelial cells injury: Circulating RNAs could explain atherosclerosis disease progression
  79. Propofol postpones colorectal cancer development through circ_0026344/miR-645/Akt/mTOR signal pathway
  80. Knockdown of lncRNA TapSAKI alleviates LPS-induced injury in HK-2 cells through the miR-205/IRF3 pathway
  81. COVID-19 severity in relation to sociodemographics and vitamin D use
  82. Clinical analysis of 11 cases of nocardiosis
  83. Cis-regulatory elements in conserved non-coding sequences of nuclear receptor genes indicate for crosstalk between endocrine systems
  84. Four long noncoding RNAs act as biomarkers in lung adenocarcinoma
  85. Real-world evidence of cytomegalovirus reactivation in non-Hodgkin lymphomas treated with bendamustine-containing regimens
  86. Relation between IL-8 level and obstructive sleep apnea syndrome
  87. circAGFG1 sponges miR-28-5p to promote non-small-cell lung cancer progression through modulating HIF-1α level
  88. Nomogram prediction model for renal anaemia in IgA nephropathy patients
  89. Effect of antibiotic use on the efficacy of nivolumab in the treatment of advanced/metastatic non-small cell lung cancer: A meta-analysis
  90. NDRG2 inhibition facilitates angiogenesis of hepatocellular carcinoma
  91. A nomogram for predicting metabolic steatohepatitis: The combination of NAMPT, RALGDS, GADD45B, FOSL2, RTP3, and RASD1
  92. Clinical and prognostic features of MMP-2 and VEGF in AEG patients
  93. The value of miR-510 in the prognosis and development of colon cancer
  94. Functional implications of PABPC1 in the development of ovarian cancer
  95. Prognostic value of preoperative inflammation-based predictors in patients with bladder carcinoma after radical cystectomy
  96. Sublingual immunotherapy increases Treg/Th17 ratio in allergic rhinitis
  97. Prediction of improvement after anterior cruciate ligament reconstruction
  98. Effluent Osteopontin levels reflect the peritoneal solute transport rate
  99. circ_0038467 promotes PM2.5-induced bronchial epithelial cell dysfunction
  100. Significance of miR-141 and miR-340 in cervical squamous cell carcinoma
  101. Association between hair cortisol concentration and metabolic syndrome
  102. Microvessel density as a prognostic indicator of prostate cancer: A systematic review and meta-analysis
  103. Characteristics of BCR–ABL gene variants in patients of chronic myeloid leukemia
  104. Knee alterations in rheumatoid arthritis: Comparison of US and MRI
  105. Long non-coding RNA TUG1 aggravates cerebral ischemia and reperfusion injury by sponging miR-493-3p/miR-410-3p
  106. lncRNA MALAT1 regulated ATAD2 to facilitate retinoblastoma progression via miR-655-3p
  107. Development and validation of a nomogram for predicting severity in patients with hemorrhagic fever with renal syndrome: A retrospective study
  108. Analysis of COVID-19 outbreak origin in China in 2019 using differentiation method for unusual epidemiological events
  109. Laparoscopic versus open major liver resection for hepatocellular carcinoma: A case-matched analysis of short- and long-term outcomes
  110. Travelers’ vaccines and their adverse events in Nara, Japan
  111. Association between Tfh and PGA in children with Henoch–Schönlein purpura
  112. Can exchange transfusion be replaced by double-LED phototherapy?
  113. circ_0005962 functions as an oncogene to aggravate NSCLC progression
  114. Circular RNA VANGL1 knockdown suppressed viability, promoted apoptosis, and increased doxorubicin sensitivity through targeting miR-145-5p to regulate SOX4 in bladder cancer cells
  115. Serum intact fibroblast growth factor 23 in healthy paediatric population
  116. Algorithm of rational approach to reconstruction in Fournier’s disease
  117. A meta-analysis of exosome in the treatment of spinal cord injury
  118. Src-1 and SP2 promote the proliferation and epithelial–mesenchymal transition of nasopharyngeal carcinoma
  119. Dexmedetomidine may decrease the bupivacaine toxicity to heart
  120. Hypoxia stimulates the migration and invasion of osteosarcoma via up-regulating the NUSAP1 expression
  121. Long noncoding RNA XIST knockdown relieves the injury of microglia cells after spinal cord injury by sponging miR-219-5p
  122. External fixation via the anterior inferior iliac spine for proximal femoral fractures in young patients
  123. miR-128-3p reduced acute lung injury induced by sepsis via targeting PEL12
  124. HAGLR promotes neuron differentiation through the miR-130a-3p-MeCP2 axis
  125. Phosphoglycerate mutase 2 is elevated in serum of patients with heart failure and correlates with the disease severity and patient’s prognosis
  126. Cell population data in identifying active tuberculosis and community-acquired pneumonia
  127. Prognostic value of microRNA-4521 in non-small cell lung cancer and its regulatory effect on tumor progression
  128. Mean platelet volume and red blood cell distribution width is associated with prognosis in premature neonates with sepsis
  129. 3D-printed porous scaffold promotes osteogenic differentiation of hADMSCs
  130. Association of gene polymorphisms with women urinary incontinence
  131. Influence of COVID-19 pandemic on stress levels of urologic patients
  132. miR-496 inhibits proliferation via LYN and AKT pathway in gastric cancer
  133. miR-519d downregulates LEP expression to inhibit preeclampsia development
  134. Comparison of single- and triple-port VATS for lung cancer: A meta-analysis
  135. Fluorescent light energy modulates healing in skin grafted mouse model
  136. Silencing CDK6-AS1 inhibits LPS-induced inflammatory damage in HK-2 cells
  137. Predictive effect of DCE-MRI and DWI in brain metastases from NSCLC
  138. Severe postoperative hyperbilirubinemia in congenital heart disease
  139. Baicalin improves podocyte injury in rats with diabetic nephropathy by inhibiting PI3K/Akt/mTOR signaling pathway
  140. Clinical factors predicting ureteral stent failure in patients with external ureteral compression
  141. Novel H2S donor proglumide-ADT-OH protects HUVECs from ox-LDL-induced injury through NF-κB and JAK/SATA pathway
  142. Triple-Endobutton and clavicular hook: A propensity score matching analysis
  143. Long noncoding RNA MIAT inhibits the progression of diabetic nephropathy and the activation of NF-κB pathway in high glucose-treated renal tubular epithelial cells by the miR-182-5p/GPRC5A axis
  144. Serum exosomal miR-122-5p, GAS, and PGR in the non-invasive diagnosis of CAG
  145. miR-513b-5p inhibits the proliferation and promotes apoptosis of retinoblastoma cells by targeting TRIB1
  146. Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p
  147. The diagnostic and prognostic value of miR-92a in gastric cancer: A systematic review and meta-analysis
  148. Prognostic value of α2δ1 in hypopharyngeal carcinoma: A retrospective study
  149. No significant benefit of moderate-dose vitamin C on severe COVID-19 cases
  150. circ_0000467 promotes the proliferation, metastasis, and angiogenesis in colorectal cancer cells through regulating KLF12 expression by sponging miR-4766-5p
  151. Downregulation of RAB7 and Caveolin-1 increases MMP-2 activity in renal tubular epithelial cells under hypoxic conditions
  152. Educational program for orthopedic surgeons’ influences for osteoporosis
  153. Expression and function analysis of CRABP2 and FABP5, and their ratio in esophageal squamous cell carcinoma
  154. GJA1 promotes hepatocellular carcinoma progression by mediating TGF-β-induced activation and the epithelial–mesenchymal transition of hepatic stellate cells
  155. lncRNA-ZFAS1 promotes the progression of endometrial carcinoma by targeting miR-34b to regulate VEGFA expression
  156. Anticoagulation is the answer in treating noncritical COVID-19 patients
  157. Effect of late-onset hemorrhagic cystitis on PFS after haplo-PBSCT
  158. Comparison of Dako HercepTest and Ventana PATHWAY anti-HER2 (4B5) tests and their correlation with silver in situ hybridization in lung adenocarcinoma
  159. VSTM1 regulates monocyte/macrophage function via the NF-κB signaling pathway
  160. Comparison of vaginal birth outcomes in midwifery-led versus physician-led setting: A propensity score-matched analysis
  161. Treatment of osteoporosis with teriparatide: The Slovenian experience
  162. New targets of morphine postconditioning protection of the myocardium in ischemia/reperfusion injury: Involvement of HSP90/Akt and C5a/NF-κB
  163. Superenhancer–transcription factor regulatory network in malignant tumors
  164. β-Cell function is associated with osteosarcopenia in middle-aged and older nonobese patients with type 2 diabetes: A cross-sectional study
  165. Clinical features of atypical tuberculosis mimicking bacterial pneumonia
  166. Proteoglycan-depleted regions of annular injury promote nerve ingrowth in a rabbit disc degeneration model
  167. Effect of electromagnetic field on abortion: A systematic review and meta-analysis
  168. miR-150-5p affects AS plaque with ASMC proliferation and migration by STAT1
  169. MALAT1 promotes malignant pleural mesothelioma by sponging miR-141-3p
  170. Effects of remifentanil and propofol on distant organ lung injury in an ischemia–reperfusion model
  171. miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway
  172. Identification of LIG1 and LIG3 as prognostic biomarkers in breast cancer
  173. MitoQ inhibits hepatic stellate cell activation and liver fibrosis by enhancing PINK1/parkin-mediated mitophagy
  174. Dissecting role of founder mutation p.V727M in GNE in Indian HIBM cohort
  175. circATP2A2 promotes osteosarcoma progression by upregulating MYH9
  176. Prognostic role of oxytocin receptor in colon adenocarcinoma
  177. Review Articles
  178. The function of non-coding RNAs in idiopathic pulmonary fibrosis
  179. Efficacy and safety of therapeutic plasma exchange in stiff person syndrome
  180. Role of cesarean section in the development of neonatal gut microbiota: A systematic review
  181. Small cell lung cancer transformation during antitumor therapies: A systematic review
  182. Research progress of gut microbiota and frailty syndrome
  183. Recommendations for outpatient activity in COVID-19 pandemic
  184. Rapid Communication
  185. Disparity in clinical characteristics between 2019 novel coronavirus pneumonia and leptospirosis
  186. Use of microspheres in embolization for unruptured renal angiomyolipomas
  187. COVID-19 cases with delayed absorption of lung lesion
  188. A triple combination of treatments on moderate COVID-19
  189. Social networks and eating disorders during the Covid-19 pandemic
  190. Letter
  191. COVID-19, WHO guidelines, pedagogy, and respite
  192. Inflammatory factors in alveolar lavage fluid from severe COVID-19 pneumonia: PCT and IL-6 in epithelial lining fluid
  193. COVID-19: Lessons from Norway tragedy must be considered in vaccine rollout planning in least developed/developing countries
  194. What is the role of plasma cell in the lamina propria of terminal ileum in Good’s syndrome patient?
  195. Case Report
  196. Rivaroxaban triggered multifocal intratumoral hemorrhage of the cabozantinib-treated diffuse brain metastases: A case report and review of literature
  197. CTU findings of duplex kidney in kidney: A rare duplicated renal malformation
  198. Synchronous primary malignancy of colon cancer and mantle cell lymphoma: A case report
  199. Sonazoid-enhanced ultrasonography and pathologic characters of CD68 positive cell in primary hepatic perivascular epithelioid cell tumors: A case report and literature review
  200. Persistent SARS-CoV-2-positive over 4 months in a COVID-19 patient with CHB
  201. Pulmonary parenchymal involvement caused by Tropheryma whipplei
  202. Mediastinal mixed germ cell tumor: A case report and literature review
  203. Ovarian female adnexal tumor of probable Wolffian origin – Case report
  204. Rare paratesticular aggressive angiomyxoma mimicking an epididymal tumor in an 82-year-old man: Case report
  205. Perimenopausal giant hydatidiform mole complicated with preeclampsia and hyperthyroidism: A case report and literature review
  206. Primary orbital ganglioneuroblastoma: A case report
  207. Primary aortic intimal sarcoma masquerading as intramural hematoma
  208. Sustained false-positive results for hepatitis A virus immunoglobulin M: A case report and literature review
  209. Peritoneal loose body presenting as a hepatic mass: A case report and review of the literature
  210. Chondroblastoma of mandibular condyle: Case report and literature review
  211. Trauma-induced complete pacemaker lead fracture 8 months prior to hospitalization: A case report
  212. Primary intradural extramedullary extraosseous Ewing’s sarcoma/peripheral primitive neuroectodermal tumor (PIEES/PNET) of the thoracolumbar spine: A case report and literature review
  213. Computer-assisted preoperative planning of reduction of and osteosynthesis of scapular fracture: A case report
  214. High quality of 58-month life in lung cancer patient with brain metastases sequentially treated with gefitinib and osimertinib
  215. Rapid response of locally advanced oral squamous cell carcinoma to apatinib: A case report
  216. Retrieval of intrarenal coiled and ruptured guidewire by retrograde intrarenal surgery: A case report and literature review
  217. Usage of intermingled skin allografts and autografts in a senior patient with major burn injury
  218. Retraction
  219. Retraction on “Dihydromyricetin attenuates inflammation through TLR4/NF-kappa B pathway”
  220. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part I
  221. An artificial immune system with bootstrap sampling for the diagnosis of recurrent endometrial cancers
  222. Breast cancer recurrence prediction with ensemble methods and cost-sensitive learning
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