Gln-362 of angiopoietin-2 mediates migration of tumor and endothelial cells through association with α5ß1 integrin.

Angiopoietin-2 (Ang-2) not only regulates angiogenesis by binding to its well known receptor Tie2 on endothelial cells but also controls sprouting of Tie2-negative angiogenic endothelial cells and invasion of Tie2-negative non-endothelial cells by binding to integrins. However, the molecular mechanism of the Ang-2/integrin association has been unclear. In this study, we found that the Gln-362 residue of Ang-2 was essential for binding to α5ß1 integrin. A Q362E Ang-2 mutant, which still bound to Tie2, failed to associate with α5ß1 integrin and was unable to activate the integrin downstream signaling of focal adhesion kinase. In addition, unlike wild-type Ang-2, the Q362E Ang-2 mutant was defective in mediating invasion of Tie2-negative glioma or Tie2-positive endothelial cells. Furthermore, the tailpiece domain of the α5 subunit in α5ß1 integrin was critical for binding to Ang-2. Taken together, these results provide a novel insight into the mechanism of integrin regulation by Ang-2, which contributes to tumor invasion and endothelial cell migration in a Tie2-independent manner.

A multimeric carcinoembryonic antigen signal inhibits the activation of human T cells by a SHP-independent mechanism: a potential mechanism for tumor-mediated suppression of T-cell immunity.

Carcinoembryonic antigen (CEA) is a well-known tumor antigen that is found in the serum of patients with various cancers and is correlated with an increased risk of cancer recurrence and metastasis. To understand the tumor environment and to develop antitumor therapies, CEA has been studied as an antigen to activate/tolerate specific T cells. In this study, we show that CEA can function as a coinhibitory molecule and can inhibit the activation of human peripheral blood mononucleated cell-derived T cells. The addition of CEA-overexpressing tumor cells or immobilized CEA dampened both cell proliferation and the expression of IL-2 and CD69 expression in T cells after TCR stimulation. The phosphorylation of ERK and translocation of NFAT were hampered in these cells, whereas the phosphorylation of proximal TCR signaling molecules such as ZAP70 and phospholipase Cγ was not affected by immobilized CEA. To determine the relevance of carcinoembryonic antigen-related cell adhesion molecule-1 and Src homology region 2 domain-containing phosphatase (SHP) molecules to CEA-mediated suppression, we tested the effect of the SHP inhibitor, NSC-87877, on CEA-mediated suppression of T cells; however, it did not reverse the effect of CEA. Collectively, these results indicate that CEA can function as a modulator of T-cell responses suggesting a novel mechanism of tumor evasion.

The Wnt inhibitor secreted Frizzled-Related Protein 1 (sFRP1) promotes human Th17 differentiation.

Wnt/ß-catenin signaling plays a crucial role during embryogenesis and tumorigenesis, and in T cells, promotes the differentiation of Th2 cells. However, the role of Wnt signals in the differentiation and maintenance of human Th17 cells remains poorly understood. We found that the higher levels of IL-17 in the synovial fluid of rheumatoid arthritis (RA) patients compared with that of osteoarthritis (OA) patients were associated with a higher concentration of sFRP1 (secreted Frizzled-Related Protein 1), an inhibitor of the Wnt/ß-catenin pathway. The addition of sFRP1 during TCR-mediated stimulation induced a significant increase in IL-17 production by both naïve and memory CD4(+) T cells. Moreover, under Th17-differentiation conditions, the addition of sFRP1 significantly reduced the requirement for TGF-ß. Mechanistically, we observed that sFRP1 significantly enhanced the phosphorylation of Smad2/3 in CD4(+) T cells upon TGF-ß stimulation and that blocking TGF-ß signaling abolished the Th17-promoting activity of sFRP1. Our findings reveal a novel function for sFRP1 as a potent inducer of human Th17-cell differentiation. Consequently, sFRP1 may represent a promising target for the treatment of Th17-mediated disease in humans.

Retinoic acid alleviates Con A-induced hepatitis and differentially regulates effector production in NKT cells.

Retinoic acid (RA) is a diverse regulator of immune responses. Although RA promotes natural killer T (NKT) cell activation in vitro by increasing CD1d expression on antigen-presenting cells (APCs), the direct effects of RA on NKT-cell responses in vivo are not known. In the present study, we demonstrated the effect of RA on the severity of Con A-induced hepatitis and molecular changes of NKT cells. First, we demonstrated that Con A-induced liver damage was ameliorated by RA. In correlation with cytokine levels in serum, RA regulated the production of IFN-γ and IL-4 but not TNF-α by NKT cells without influencing the NKT-cell activation status. However, RA did not alleviate α-GalCer-induced liver injury, even though it reduced IFN-γ and IL-4 but not TNF-α levels in serum. This regulation was also detected when liver mononuclear cells (MNCs) or NKT hybridoma cells were treated with RA in vitro. The regulatory effect of RA on NKT cells was mediated by RAR-α, and RA reduced the phosphorylation of MAPK. These results suggest that RA differentially modulates the production of effector cytokines by NKT cells in hepatitis, and the suppressive effect of RA on hepatitis varies with the pathogenic mechanism of liver injury.

Conversion of Th2 memory cells into Foxp3+ regulatory T cells suppressing Th2-mediated allergic asthma.

Genetic and epigenetic programming of T helper (Th) cell subsets during their polarization from naive Th cells establishes long-lived memory Th cells that stably maintain their lineage signatures. However, whether memory Th cells can be redifferentiated into another Th lineage is unclear. In this study, we show that Ag-specific memory Th cells were redifferentiated into Foxp3(+) T cells by TGF-beta when stimulated in the presence of all-trans retinoic acid and rapamycin. The "converted" Foxp3(+) T cells that were derived from Th2 memory cells down-regulated GATA-3 and IRF4 and produced little IL-4, IL-5, and IL-13. Instead, the converted Foxp3(+) T cells suppressed the proliferation and cytokine production of Th2 memory cells. More importantly, the converted Foxp3(+) T cells efficiently accumulated in the airways and significantly suppressed Th2 memory cell-mediated airway hyperreactivity, eosinophilia, and allergen-specific IgE production. Our findings reveal the plasticity of Th2 memory cells and provide a strategy for adoptive immunotherapy for the treatment of allergic diseases.

Effect of Nefopam on Dysesthesia, Postoperative Pain, and Satisfaction in Patients with Lumbar Spinal Stenosis Undergoing Spine Surgery: A Double-Blind, Randomized Study.

Postoperative residual pain and dysesthesia in patients with lumbar spinal stenosis (LSS) can reduce patient satisfaction. We investigated the effects of nefopam on dysesthesia, postoperative pain, and satisfaction in patients with LSS who underwent spine surgery. A total of 73 patients were randomly assigned to two groups: the nefopam group (n = 35), receiving a 20 mL normal saline-based solution containing nefopam 20 mg, and the control group (n = 38), which received 20 mL of normal saline 1 h before the end of the operation. Postoperative incisional pain, dysesthesia scores, and overall satisfaction with postoperative pain management were evaluated. The severity of dysesthesia within 12 and 24 h in the nefopam group was significantly lower than that in the control group (2.3 ± 1.9 and 1.7 ± 1.6 vs. 3.3 ± 2.1, and 2.6 ± 1.9, respectively; p = 0.029 and p = 0.048). Satisfaction scores for postoperative pain management were significantly higher in the nefopam group (3.7 ± 0.6 vs. 3.1 ± 1.0, respectively; p = 0.006). The administration of nefopam effectively reduced the severity of dysesthesia within 24 h of surgery in geriatric patients undergoing spine surgery and increased patient satisfaction with postoperative pain management.

Investigating preoperative myoglobin level as predictive factor for acute kidney injury following cardiac surgery with cardiopulmonary bypass: a retrospective observational study.

BACKGROUND: Early identification of patients at risk of AKI after cardiac surgery is of critical importance for optimizing perioperative management and improving outcomes. This study aimed to identify the association between preoperative myoglobin levels and postoperative acute kidney injury (AKI) in patients undergoing valve surgery or coronary artery bypass graft surgery (CABG) with cardiopulmonary bypass. METHODS: This retrospective study included 293 patients aged over 17 years who underwent valve surgery or CABG with cardiopulmonary bypass. We excluded 87 patients as they met the exclusion criteria. Therefore, 206 patients were included in the final analysis. The patients... demographics as well as intraoperative and postoperative data were collected from electronic medical records. AKI was defined according to the Acute Kidney Injury Network classification system. RESULTS: Of the 206 patients included in this study, 77 developed AKI. The patients who developed AKI were older, had a history of hypertension, underwent valve surgery with concomitant CABG, had lower preoperative hemoglobin levels, and experienced prolonged extracorporeal circulation (ECC) times. Multivariate logistic regression analysis revealed that preoperative myoglobin levels and ECC time were correlated with the development of AKI. A higher preoperative myoglobin level was an independent risk factor for the development of cardiac surgery-associated AKI. CONCLUSIONS: Higher preoperative myoglobin levels may enable physicians to identify patients at risk of developing AKI and optimize management accordingly.

Intrathecal hydromorphone added to hyperbaric bupivacaine for postoperative pain relief after knee arthroscopic surgery: a prospective, randomised, controlled trial.

BACKGROUND AND OBJECTIVE: Adding opioid to spinal anaesthetic provides additional analgesia during the postoperative period. The purpose of this study was to determine the dose of intrathecal hydromorphone necessary to achieve postoperative pain relief after arthroscopic knee surgery. METHODS: In a prospective, double-blinded parallel, placebo-controlled manner, 60 patients who were undergoing unilateral knee arthroscopy randomly received unilateral spinal anaesthesia with 0.5% hyperbaric bupivacaine 6 mg combined with 0.0, 2.5, 5.0 or 10.0 µg per 0.05 ml hydromorphone. Fifteen patients were assigned to receive each dose. The visual analogue pain scores (VAPSs) were measured at 30 min and 2, 4, 6, 12 and 24 h postoperatively, and the side-effects of hydromorphone were recorded. RESULTS: The postoperative VAPSs at 4, 6 and 12 h for the 5 and 10 µg hydromorphone groups were significantly decreased, compared to the control group. The 2.5 µg hydromorphone group had lower VAPS only at 4 and 6 h postoperatively. Nausea was significantly increased in the 10 µg hydromorphone group (46.6%). CONCLUSION: The analgesic effects of 5 and 10 µg intrathecal hydromorphone provided satisfactory pain relief for 12 h postoperatively and nausea increased significantly in a dose-dependent manner.

The effect of alpha-2A adrenergic receptor (ADRA2A) genetic polymorphisms on the depth of sedation of dexmedetomidine: a genetic observational pilot study.

BACKGROUND: The genetic polymorphisms of the alpha-2A adrenergic receptor (ADRA2A), which plays a significant role in sedation, anxiety relief, and antinociception, particularly in dexmedetomidine, may differ in the degree of sedation. This study aimed to investigate the effect of the genetic polymorphisms of ADRA2A (rs11195418, rs1800544, rs2484516, rs1800545, rs553668, rs3750625) on the sedative effects of dexmedetomidine. METHODS: A total of 131 patients aged 50 years or more from May 2018 to August 2019 were included in this study. The ADRA2A gene variants were evaluated using the TaqMan Assay. Dexmedetomidine diluted in normal saline to a concentration of 4µg.mL-1 was infused at a dose of 2µg.kg-1 to achieve procedural sedation (modified Ramsay sedation scale 4 [mRSS 4]). RESULTS: A total of 131 patients were evaluated. The genetic polymorphisms (rs11195418) of the ADRA2A receptor gene demonstrated no variation in our participants. The ADRA2A receptor gene polymorphisms (rs1800544, rs2484516, rs1800545, rs553668, and rs3750625) exhibited no differences in total dexmedetomidine doses (p>0.217), bispectral index at mRSS 4 (p>0.620), and time to obtain mRSS 4 (p>0.349). CONCLUSION: This study suggested that the genetic polymorphisms of ADRA2A did not affect the sedative efficacy of dexmedetomidine.

The state of anesthesia in South Korea: a national survey of the status of anesthetic service activity in 2014-2016.

BACKGROUND: Because the quality of anesthesia affects the surgical outcome, the aim of this study was to investigate the current status of anesthetic services performed by anesthesiologists and non-anesthesiologists in South Korea from 2014 to 2016 and to compare the results with data from 2011 to 2013. METHODS: The claimed anesthesia services at medical institutions with employed anesthesiologists and the claims for an invitation fee for an anesthesiologist at medical institutions without employed anesthesiologists were regarded as anesthetic services performed by an anesthesiologist. From 2014 to 2016, the employment of anesthesiologists according to the type of medical institution, the status of anesthetic services according to the presence or absence of employed anesthesiologists, and status of anesthetic services at medical institutions without employed anesthesiologists were analyzed. RESULTS: The proportion of medical institutions that employed anesthesiologists slightly increased from 27.8% in 2014 to 28.8% in 2016. General anesthesia was more concentrated at higher medical institutions, and most anesthesias were performed by an anesthesiologist. The proportion of spinal anesthesia, epidural anesthesia, and brachial plexus performed by non-anesthesiologists was 11%, 15%, and 16.5%, respectively. Intravenous anesthesia performed by non-anesthesiologists was 58% and has increased compared to the past. CONCLUSIONS: The employment of anesthesiologists has increased with time, and general anesthesiology was mostly performed by anesthesiologists. However, since the proportion of anesthetic services performed by non-anesthesiologists in regional anesthesia and intravenous anesthesia was maintained high, it is necessary to find ways to expand the safety of anesthetic services.

Comparison of the effects of cranial electrotherapy stimulation and midazolam as preoperative treatment in geriatric patients: A CONSORT-compliant randomized controlled trial.

BACKGROUND: Although midazolam is widely administered as an anxiolytic premedication, it may cause over-sedation and hypoxia in geriatric patients. Cranial electrotherapy stimulation (CES) is a nonpharmacological device with anxiolytic effect. This study compared the effects of CES and midazolam as a preoperative treatment in geriatric patients. METHODS: Eighty patients, under the age of 65 to 79 years, undergoing general anesthesia were randomly assigned into midazolam premedication group (M group, n = 40) or CES pretreatment group (CES group, n = 40). The patients in the M group were intramuscularly injected with midazolam (0.07 mg/kg) 30 minutes before receiving general anesthesia. The patients in the CES group received 20 minutes of CES pretreatment on the day before and on the morning of the surgery. RESULTS: In the preoperative holding area, the anxiety score (P = .02) and the sedation score (P < .001) were significantly lower in the CES group compared with those in the M group. The oxygen saturations at the preoperative holding area and the operating room were significantly higher in the CES group than those in the M group (P < .001). CONCLUSION: CES pretreatment relieved preoperative anxiety with less risk of over-sedation and respiratory depression than midazolam premedication in geriatric patients.

A Comparison of the Anesthetic Methods for Recurrence Rates of Bladder Cancer after Transurethral Resection of Bladder Tumors Using National Health Insurance Claims Data of South Korea.

Bladder cancers have high recurrence rates and are usually removed via transurethral resection of bladder tumor (TURBT). Recently, some reports showed that the anesthetic method may affect the recurrence rates of bladder cancers. The purpose of this population-based study was to compare the effect of anesthetic methods with the recurrence rates of bladder cancers in South Korea. A total of 4439 patients were reviewed retrospectively using the data of the Korean National Health Insurance (NHI) claims database from January 2007 to December 2011. Patients were divided into 2 groups who received general (n = 3767) and regional anesthesia (n = 582), and were followed up until September 2017. Propensity score matching was conducted to reduce the effect of confounding factors. After using propensity score matching with a multivariable Cox regression model, age (p < 0.001), sex (p < 0.001), hypertension (p = 0.003), diabetes mellitus (p = 0.001), and renal disease (p < 0.001) were significantly associated with bladder cancer recurrence. However, there were no significant differences in the recurrence rates of bladder cancers in patients who received general anesthesia and spinal anesthesia for TURBTs. This study revealed that there is no relationship between the anesthetic method and bladder cancer recurrence. Either general anesthesia or regional anesthesia can be used depending on the situation in patients receiving TURBT. Future prospective studies are warranted to confirm the association between the anesthetic method and the recurrence rates of bladder cancer.

Proposal of pharmacogenetics-based warfarin dosing algorithm in Korean patients.

Warfarin is a commonly prescribed anticoagulant drug for the prevention of thromboembolic disorders. We investigated the contribution of genetic variations of four genes and clinical factors to warfarin dose requirement and provided a warfarin-dosing algorithm based on genetic and clinical variables in Korean patients. We recruited 564 Korean patients on stable anticoagulation. Single nucleotide polymorphisms (SNPs) for the VKORC1, CYP2C9, CYP4F2 and GGCX were analyzed. Using multiple regression analysis, we developed a model to predict the warfarin requirement. The SNPs of VKORC1, CYP2C9, CYP4F2 and GGCX showed significant correlation with warfarin dose. Patients with the 3730AA genotype received significantly higher doses of warfarin than those with the 3730GG (P=0.0001). For CYP2C9, the highest maintenance dose was observed in the patients with wild-type genotype compared with the variant allele carriers (P<0.0001). The multiple regression model including age, gender, body surface area (BSA), international normalized ratio (INR) and four genetic polymorphisms accounted for 35% of total variations in warfarin dose (R(2)=0.3499; P<0.0001). This study shows that age, gender, BSA, INR and VKORC1, CYP2C9 and CYP4F2 polymorphism affect warfarin dose requirements in Koreans. Translation of this knowledge into clinical guidelines for warfarin prescription may contribute to improve the efficacy and safety of warfarin treatment for Korean patients.

Morphine attenuates endothelial cell adhesion molecules induced by the supernatant of LPS-stimulated colon cancer cells.

A large reservoir of bacterial lipopolysaccharide (LPS) is available in the colon and this could promote colon cancer metastasis by enhancing tumor cell adhesion, intravasation, and extravasation. Furthermore, adhesion molecules like ICAM-1, VCAM-1, and E-selectin play important roles in the adhesion of tumor cells to endothelium. This study was designed to determine whether morphine can attenuate the expressions of adhesion molecules up-regulated by the supernatant of LPS-stimulated HCT 116 colon cancer cells (LPS-Sup). In this study, we divided to three groups by cell-growth medium of human umbilical vascular endothelial cells (HUVECs): the control group was incubated in growth factor-free endothelial medium, the Sup group was incubated in the supernatant of HCT 116 cells (Sup), and the LPS-Sup group was incubated in LPS-Sup. To observe effect of morphine to the adhesion molecules expressions in the LPS-Sup group, we co-treated morphine with LPS or added it to LPS-Sup. Adhesion molecule expressions on HUVECs in all three groups were measured during incubation period. Consquentially, ICAM-1, VCAM-1, and E-selectin expressions on HUVECs were significantly lower when morphine was co-treated with LPS than not co-treated. Thus, we suggest that morphine affects the expressions of adhesion molecules primarily by attenuating LPS stimuli on tumor cells.

Morphine postconditioning attenuates ICAM-1 expression on endothelial cells.

The purpose of this study is to determine 1) whether morphine post condition (MPostC) can attenuate the intercellular adhesion molecules-1 (ICAM-1) expression after reoxygenation injury and 2) the subtype(s) of the opioid receptors (ORs) that are involved with MPostC. Human umbilical vein endothelial cells (HUVECs) were subjected to 6 hr anoxia followed by 12 hr reoxygenation. Three morphine concentrations (0.3, 3, 30 µM) were used to evaluate the protective effect of MPostC. We also investigated blockading the OR subtypes' effects on MPostC by using three antagonists (a µ-OR antagonist naloxone, a κ-OR antagonist nor-binaltorphimine, and a δ-OR antagonist naltrindole) and the inhibitor of protein kinase C (PKC) chelerythrine. As results, the ICAM-1 expression was significantly reduced in the MPostC (3, 30 µM) groups compared to the control group at 1, 6, 9, and 12 hours reoxygenation time. As a consequence, neutrophil adhesion was also decreased after MPostC. These effects were abolished by co administering chelerythrine, nor-binaltorphimine or naltrindole, but not with naloxone. In conclusion, it is assumed that MPostC could attenuate the expression of ICAM-1 on endothelial cells during reoxygenation via the κ and δ-OR (opioid receptor)-specific pathway, and this also involves a PKC-dependent pathway.

Impact of age on the incidence of complications after liver transplantation: A single-center retrospective study.

BACKGROUND AND OBJECTIVE: Advances in surgical technique, postoperative management, and immunosuppressive therapy have led to a steady increase in the number of patients undergoing organ transplantation. This study aimed to compare the incidence of postoperative complications between young and elderly patients undergoing liver transplantation (LT) at a single university hospital. METHOD: The medical records of 253 patients who underwent LT between January 2010 and July 2017 were retrospectively reviewed. The patients were divided into two groups: those younger than 65 years (group Y, n=231) and those older than 65 years (group O, n=22). Data on patient demographics, perioperative management, and postoperative complications were collected. RESULTS: The patients' baseline characteristics, including underlying diseases and the Model for End-Stage Liver Disease scores, were not different between groups. Preoperative laboratory findings were not significantly different between the two groups, except for hemoglobin level. The total amounts of infused fluid and packed red blood cells were higher in group O than in group Y. The postoperative plasma creatinine level was higher in group O than in group Y; however, the incidence of postoperative complications was not considerably different between the two groups. In addition, there was no difference in the survival rate after LT depending on age. CONCLUSION: With the development of medical technology, LT in elderly patients is not an operation to be avoided, and the prognosis is expected to improve. Therefore, continuous efforts to understand the disease characteristics and physical differences in elderly patients who require LT are essential.

Postoperative hypoalbuminemia is an independent predictor of 1-year mortality after surgery for geriatric intertrochanteric femoral fracture: A retrospective cohort study.

ABSTRACT: Preoperative hypoalbuminemia from malnutrition is associated with increased morbidity and mortality after geriatric hip fracture surgery. However, little is known regarding the correlation between postoperative hypoalbuminemia and mortality. This study aimed to evaluate whether postoperative hypoalbuminemia could predict 1-year mortality after intertrochanteric femoral fracture surgery in elderly patients.The medical records of 263 geriatric patients (age ≥65 years) who underwent intertrochanteric femoral fracture surgery between January 2013 and January 2016 in a single hospital were reviewed retrospectively. The patients were allocated to 2 groups based on lowest serum albumin levels within 2 postoperative days (≥3.0 g/dL [group 1, n = 46] and <3.0 g/dL [group 2, n = 217]. Data between the non-survival and survival groups were compared. Multivariable logistic regression analysis was conducted to identify the independent predictor for 1-year mortality.The 1-year mortality rate was 16.3% after intertrochanteric femoral fracture surgery. Multivariable logistic regression analysis revealed that postoperative hypoalbuminemia was significantly associated with 1-year mortality (adjusted odds ratio, 8.03; 95% confidence interval, 1.37-47.09; P = .021). The non-survival group showed a significantly increased incidence of postoperative hypoalbuminemia (95.4% vs 80.0%, P = .015) and intensive care unit admission (11.6% vs 2.7%, P = .020), older age (82.5 ±â€Š5.8 years vs 80.0 ±â€Š7.2 years, P = .032), lower body mass index (20.1 ±â€Š3.2 kg/m2 vs 22.4 ±â€Š3.8 kg/m2, P < .001), and increased amount of transfusion of perioperative red blood cells (1.79 ±â€Š1.47 units vs 1.43 ±â€Š2.08 units, P = .032), compared to the survival group.This study demonstrated that postoperative hypoalbuminemia is a potent predictor of 1-year mortality in geriatric patients undergoing intertrochanteric femoral fracture surgery. Therefore, exogenous albumin administration can be considered to improve postoperative outcomes and reduce the risk of mortality after surgery for geriatric hip fracture.

Effects of cranial electrotherapy stimulation on preoperative anxiety and blood pressure during anesthetic induction in patients with essential hypertension.

OBJECTIVE: Cranial electrotherapy stimulation (CES) is a non-invasive treatment that improves symptoms such as anxiety and pain. The purpose of this study was to analyze the effect of CES pretreatment on levels of preoperative anxiety, pain, and hemodynamic responses-especially changes in blood pressure-during anesthetic induction in patients with essential hypertension. METHODS: Eighty patients undergoing general anesthesia were randomly assigned to receive either no pretreatment (control group, n = 40) or CES pretreatment (CES group, n = 40). Anxiety scores, systolic and diastolic blood pressures, mean arterial pressure, and heart rate were measured in the general ward the evening before surgery, as well as in the preoperative holding area, operating room, and after intubation. Withdrawal responses to rocuronium injection were also measured. RESULTS: Anxiety scores in the operating room were significantly lower in the CES group. Withdrawal responses to rocuronium injection were also significantly lower in the CES group. There were no significant differences in hemodynamic values between the two groups. CONCLUSIONS: CES pretreatment reduces both preoperative anxiety levels and withdrawal responses to rocuronium injection. However, it does not have a significant effect on hemodynamic responses.

Liver Transplant Patients with High Levels of Preoperative Serum Ammonia Are at Increased Risk for Postoperative Acute Kidney Injury: A Retrospective Study.

Acute kidney injury (AKI) is one of the most frequent postoperative complications after liver transplantation (LT). Increased serum ammonia levels due to the liver disease itself may affect postoperative renal function. This study aimed to compare the incidence of postoperative AKI according to preoperative serum ammonia levels in patients after LT. Medical records from 436 patients who underwent LT from January 2010 to February 2020 in a single university hospital were retrospectively reviewed. The patients were then categorized according to changes in plasma creatinine concentrations within 48 h of LT using the Acute Kidney Injury Network criteria. A preoperative serum ammonia level above 45 mg/dL was associated with postoperative AKI (p < 0.0001). Even in patients with a normal preoperative creatinine level, when the ammonia level was greater than 45 µg/dL, the incidence of postoperative AKI was significantly higher (p < 0.0001); the AKI stage was also higher in this group than in the group with preoperative ammonia levels less than or equal to 45 µg/dL (p < 0.0001). Based on the results of our research, an elevation in preoperative serum ammonia levels above 45 µg/dL is related to postoperative AKI after LT.

Liver Transplant Patients with High Preoperative Serum Bilirubin Levels Are at Increased Risk of Postoperative Delirium: A Retrospective Study.

Postoperative delirium is a common complication after liver transplantation (LT). A high model for end-stage liver disease (MELD) score is an independent risk factor for postoperative delirium, but it is unclear which of the components of this score are risk indicators. The aim of this study was to analyze the incidence of postoperative delirium according to the preoperative serum bilirubin level, a component of the MELD score, in patients who underwent LT. The medical records of 325 patients who underwent LT from January 2010 to February 2019 at a single university hospital were retrospectively reviewed. The patients were divided into two groups: those who experienced postoperative delirium (Delirium group, n = 69) and those who did not (Control group, n = 256). Data on the patients' demographic characteristics, perioperative management, and postoperative complications were collected. Mean preoperative bilirubin level was higher in the Delirium group than in the Control group (p < 0.0001). In the Delirium group, 54 (78.26%) patients had preoperative bilirubin levels above 3.5 mg/dL. In the multivariate analysis, preoperative bilirubin above 3.5 mg/dL was associated with postoperative delirium (p = 0.002). Therefore, preoperative hyperbilirubinemia is an independent risk factor for postoperative delirium.