Uplift modeling to predict individual treatment effects of renal replacement therapy in sepsis-associated acute kidney injury patients.

Renal replacement therapy (RRT) is a crucial treatment for sepsis-associated acute kidney injury (S-AKI), but it is uncertain which S-AKI patients should receive immediate RRT. Identifying the characteristics of patients who may benefit the most from RRT is an important task. This retrospective study utilized a public database and enrolled S-AKI patients, who were divided into RRT and non-RRT groups. Uplift modeling was used to estimate the individual treatment effect (ITE) of RRT. The validity of different models was compared using a qini curve. After labeling the patients in the validation cohort, we characterized the patients who would benefit the most from RRT and created a nomogram. A total of 8289 patients were assessed, among whom 591 received RRT, and 7698 did not receive RRT. The RRT group had a higher severity of illness than the non-RRT group, with a Sequential Organ Failure Assessment (SOFA) score of 9 (IQR 6,11) vs. 5 (IQR 3,7). The 28-day mortality rate was higher in the RRT group than the non-RRT group (34.83% vs. 14.61%, p < 0.0001). Propensity score matching (PSM) was used to balance baseline characteristics, 458 RRT patients and an equal number of non-RRT patients were enrolled for further research. After PSM, 28-day mortality of RRT and non-RRT groups were 32.3% vs. 39.3%, P = 0.033. Using uplift modeling, we found that urine output, fluid input, mean blood pressure, body temperature, and lactate were the top 5 factors that had the most influence on RRT effect. The area under the uplift curve (AUUC) of the class transformation model was 0.068, the AUUC of SOFA was 0.018, and the AUUC of Kdigo-stage was 0.050. The class transformation model was more efficient in predicting individual treatment effect. A logistic regression model was developed, and a nomogram was drawn to predict whether an S-AKI patient can benefit from RRT. Six factors were taken into account (urine output, creatinine, lactate, white blood cell count, glucose, respiratory rate). Uplift modeling can better predict the ITE of RRT on S-AKI patients than conventional score systems such as Kdigo and SOFA. We also found that white blood cell count is related to the benefits of RRT, suggesting that changes in inflammation levels may be associated with the effects of RRT on S-AKI patients.

Serum lactate monitoring may help to predict neurological function impairment caused by acute metabolism crisis.

To investigate the predictive value of serum lactate on neurological function impairment and the possible etiology. In this retrospective study, all the adult patients admitted to ICU more than 24 h after general anesthesia elective neurosurgery from January 2018 to January 2019 were recruited. The data of the serum lactate every 8 h during the 24 h of ICU admission were acquired and analyzed. 169 patients were included in the outcomes analysis. The average serum lactate after ICU admission was 3.7(3.4-4.1) mmol/L, higher than normal, and serum lactate elevated commonly after neurosurgery. The serum lactate at ICU admission (lactateserum0h) was not correlated with the outcomes, whereas the predictive value increased as the monitoring time was extended. The result indicated that lactateserum8h, the lactateserum16h, and the lactateserum24h were correlated with the primary outcome (difference of GCS scores before the surgery and after 24 h of ICU admission (ΔGCS24h) (p < 0.05). The lactateserum16h and the lactateserum 24 h were correlated with all the outcomes except for the hospital LOS. The ROC curve suggested that the lactateserum24h achieved the best predictive value. Patients with serum lactate non-recovered trend after 24 h of ICU stay had decreased GCS scores and vice versa, as indicated by the graph of the dynamic changes in the serum lactate. The predictive value of the serum glucose/serum lactate ratio at ICU admission (G/Lserum) was analyzed, and the result indicated that it was correlated with the ΔGCS24h (p < 0.05), the G/Lserum can predict neurological impairment earlier. Dynamic serum lactate monitoring and the G/Lserum at ICU admission have predict value on neurological function impairment after neurosurgery which might be attributed to ACMC.

Missed diagnosis of acute kidney injury in older patients with invasive mechanical ventilation: a multicenter retrospective study.

OBJECTIVES: Patients who undergo mechanical ventilation (MV) are at higher risk of suffering from acute kidney injury (AKI). However, whether AKI is diagnosed in all patients and the association between AKI and mortality are unclear. METHODS: This was a retrospective, observational, multicenter cohort study conducted from January 2008 to December 2020 that included 3271 consecutive older patients (≥ 75 years) who received invasive MV from four medical centers in Chinese PLA General Hospital. AKI was diagnosed according to the serum creatinine (Scr)-based Kidney Disease: Improving Global Outcomes guidelines by an absolute increase in Scr of ≥ 26.5 µmol/L within the first 48 h of MV. The outcomes of patients with and without AKI and whether AKI was recognized were compared. RESULTS: A total of 1292 patients were included in the final evaluation. Three hundred seventy-six patients (29.1%) fulfilled the diagnostic criteria. Among the 376 AKI patients, the recognition rate and nonrecognition rate were 62.8% (236/376) and 37.2% (140/376), respectively. The overall 90-day mortality rate was 45.2% (584/1,292), which was dramatically increased in unrecognized AKI patients and recognized AKI compared to non-AKI patients (70.7% vs. 54.7% vs. 38.9%, respectively, P < 0.001). The survival of patients with recognized AKI was better than that of patients with unrecognized AKI. Multivariate logistic regression analysis revealed that recognized AKI was significantly associated with mean arterial pressure, positive end-expiratory pressure, uric acid, baseline Scr, and peak Scr. AKI was identified as an independent predictor of all-cause 90-day mortality (recognized AKI vs. non-AKI: HR = 1.722; 95% CI = 1.399-2.119; P < 0.001 and unrecognized AKI vs. non-AKI: HR = 2.632; 95% CI = 2.081-3.329; P < 0.001). CONCLUSIONS: AKI is a common complication in older patients undergoing MV, with substantial underdiagnosis and undertreatment. Interventions for improving the diagnosis of AKI are urgently needed.

Mass brain tissue lost after decompressive craniectomy: A case report.

BACKGROUND: The brain is the most important organ to maintain life. However, the amount of brain tissue required for maintaining life in humans has not been previously reported. CASE SUMMARY: A 33-year-old woman fell from the third floor three months before admission to our department. She received a decompressive craniectomy soon after injury. After the operation, operative incision disunion occurred due to the high pressure. Brain tissue flowed from the incision, and intracranial infection occurred. She fell into deep coma and was sent to our hospital. Her right temporal surgical incision was not healed and had a cranial defect of 10 cm × 10 cm. Her intracranial cavity was observed from the skull defect, and the brain tissue was largely lost. In addition, no brain tissue was observed by visual inspection. Cranial computed tomography showed that only a small amount of brain tissue density shadow was compressed in the cerebellum and brainstem. Four days after hospitalization in our hospital, her parents transferred her to a hospital near her hometown. The patient died six days after discharge from our hospital. CONCLUSION: This rare case provides some proof of the importance of the brainstem in the maintenance of cardiac rhythm and vascular tension. Neurosurgeons should carefully protect brainstem neurons during operations. Clinicians can maintain the cardiac rhythm of patients who lose their major brain tissue with modern technology, but the family of the patients should be aware of death and end-life care.

Association Between the Severity of Early Acute Kidney Injury and Subsequent in-Hospital Complications and 90-Day Mortality in Geriatric Patients Receiving Invasive Mechanical Ventilation.

Purpose: Acute kidney injury (AKI) in elderly patients is associated with higher hospital mortality. However, the relationship between AKI and peri-intubation complications is unclear. Methods: This retrospective, observational, multicenter cohort study enrolled 3271 consecutive elderly patients (≥75 years) who received invasive mechanical ventilation (MV) in four medical centers of Chinese PLA General Hospital from 2008 to 2020. AKI was diagnosed according to the 2012 KDIGO criteria by an absolute increase in serum creatinine of ≥26.5 µmol/L within the first 48 hours of MV. We recorded subsequent in-hospital complications, including incident gastrointestinal bleeding, new-onset electrolyte imbalances, severe hypoxemia, hypoalbuminemia, cardiovascular instability and all-cause 90-day mortality. Results: A total of 1292 patients were included in the final evaluation, with 29.1% presenting AKI (stage 1: 31.4%, stage 2: 35.1%, stage 3: 33.5%). Multiple regression analyses show that more advanced AKI increased the risk of MAP <65 mmHg (stage 1: OR=1.833, P=0.002; stage 2: OR= 4.653, P<0.001; stage 3: OR=4.834, P<0.001) and SBP <90 mmHg (stage 1: OR=1.644, P=0.014; stage 2: OR=3.701, P<0.001; stage 3: OR=5.750, P<0.001), a new need for or requiring an increased dose of vasopressors (stage 1: OR=1.623, P=0.014; stage 2: OR=3.250, P<0.001; stage 3: OR=12.132, P<0.001), gastrointestinal bleeding (stage 1: OR=1.102, P=0.669; stage 2: OR=1.471, P=0.060; stage 3: OR=2.377, P<0.001), severe hypoxia (stage 1: OR=1.213, P=0.399; stage 2: OR=1.449, P=0.077; stage 3: OR=2.214, P<0.001) and all-cause 90-day mortality (stage 1: OR =0.935; P=0.741; stage 2: OR=1.888; P=0.001; stage 3: OR=12.584; P<0.001). Conclusion: Our study suggests that the presence of AKI within the first 48 hours of MV in geriatric patients is associated with a higher risk for postintubation complications and 90-day mortality. Moreover, the risk of complications was greater for patients with more severe AKI.

The role of BKCa in endometrial cancer HEC-1-B cell proliferation and migration.

BKCa is a large conductance calcium activated potassium channel ubiquitously expressed in various cell types. Accumulating evidence demonstrates that BKCa is aberrantly expressed in many malignancies, involving in cancerous behaviors such as cell proliferation and migration. In this study, we investigated the functional role of BKCa in endometrial cancer HEC-1-B cells. Overexpression of BKCa by plasmid transfection enhanced endometrial cancer cell proliferation and migration. Conversely, silence of BKCa by lentivirus mediated RNAi system not only inhibited proliferation and migration but also impaired tumor growth in vivo. Patch clamp assay identified the BKCa currents in HEC-1-B cells, which was supported by the observation of channel activation or inhibition in response to the specific opener (NS1619) or blocker (IBTX) of BKCa. Moreover, NS1619 significantly increased cell proliferation and migration while IBTX exhibited the opposite effects. In summary, these data suggested an important role of BKCa in proliferation and migration of endometrial cancer HEC-1-B cells. Thus, BKCa may be established as a potential therapeutic target in endometrial cancer.

Cytotoxic CD4+ T cells are correlated with better prognosis in Han Chinese grade II and grade III glioma subjects and are suppressed by PD-1 signaling.

PURPOSE: Malignant gliomas are the most common tumors in the central nervous system with a poor prognosis. Recently, CD4+ cytotoxic T cells (CTLs) are being increasingly recognized as possessing antitumor capacity. However, their presence, activity and regulation in glioma have not been investigated in detail. METHODS: To examine this, 72 grade II and grade III Han Chinese glioma patients and 30 Han Chinese healthy controls were investigated. RESULTS: We found that compared to healthy controls, glioma patients had significantly upregulated frequencies of circulating CD4+ CTLs, identified by the expression of granzyme A (GzmA), granzyme B (GzmB) and/or perforin. The stimulated CD4+ CTLs in grade II and grade III glioma patients also had less proliferative ability than those in healthy controls, a feature of suppression that progressed with tumor grade. The frequencies of GzmB-expressing circulating CD4+ CTLs were directly associated with prognosis. We hypothesized that the programed death 1 (PD-1)/PD-ligand 1 (L1) interaction possibly contributed to the suppression of CD4+ CTLs in grade II and grade III glioma, since an upregulation of PD-1 was observed on CD4+ CTLs in glioma compared to those in the healthy individuals. Blockade of the PD-1/PD-L1 interaction with neutralizing antibodies significantly increased the proliferation and granzyme or perforin production by CD4+ CTLs in grade II and grade III glioma patients. CONCLUSIONS: These data suggest that the CD4+ CTLs in grade II and grade III glioma patients contribute to antitumor immunity and could be suppressed by PD-1 signal transduction.

Inhibition of CD8+ T cells and elimination of myeloid cells by CD4+ Foxp3- T regulatory type 1 cells in acute respiratory distress syndrome.

Acute lung injury and acute respiratory distress syndrome (ARDS) are caused by rapid-onset bilateral pulmonary inflammation. We therefore investigated the potential role of interleukin (IL)-10+ CD4+ Tr1 cells, a regulatory T cell subset with previously identified immunosuppressive functions, in ARDS patients. We first showed that circulating Tr1 cells were upregulated in active and resolved ARDS patients compared to healthy controls and pneumonia patient controls. A significant fraction of these Tr1 cells expressed granzyme B and perforin, while most Tr1 cells did not express interferon gamma (IFN-γ), IL-4, IL-17 or FOXP3, suggesting that the effector functions of these Tr1 cells were primarily mediated by IL-10, granzyme B, and perforin. Indeed, Tr1 cells effectively suppressed CD8+ T cell IFN-γ production and induced lysis of monocytes and dendritic cells in vitro. The elimination of myeloid antigen-presenting cells depended on granzyme B production. We also discovered that Tr1 cells could be identified in the bronchoalveolar lavage fluid collected from ARDS patients. All these results suggested that Tr1 cells possessed the capacity to downregulate inflammation in ARDS. In support of this, we found that ARDS patients who resolved the inflammation and survived the syndrome contained significantly higher levels of Tr1 cells than ARDS patients who succumbed to the syndrome. Overall, this report added a novel piece of evidence that ARDS could be intervened by regulatory T cell-mediated suppressive mechanisms.

Early Recruitment of IL-10-Producing B Cells Into Alveoli Improved the Resolution of Acute Lung Injury.

BACKGROUND: Acute lung injury (ALI) is characterized by rapid induction of inflammation at the alveolar-capillary membrane, and immunosuppressive mechanisms were shown to contribute to its resolution. Despite the central role of lymphocytes in initiating and mediating an inflammatory response, their influx dynamics in ALI has not been examined. METHODS: We collected mini-BAL samples from the lung of ALI patients over a maximum period of 7 days, and examined the lymphocyte composition. RESULTS: CD3+CD4+IFN-gamma+ Th1 cells were detected early on in all patients examined, while IL-10-producing B cells and CD3+CD4+CD25hiFoxp3+ Treg cells appeared later. Interestingly, IL-10-producing B cells appeared earlier than Tregs in most subjects, which possibly exerted anti-inflammatory function before Tregs. We then found that in patients with earlier recruitment of IL-10-producing B cells, the magnitude of Th1 inflammation decreased significantly over time, which was not observed in patients with later recruitment of IL-10-producing B cells. Furthermore, early IL-10-producing B cell recruiters also had significantly earlier recruitment of Tregs and better survival than late IL-10-producing B cell recruiters. CONCLUSION: This study provided data on the alveolar infiltration of lymphocytes during ALI, which suggested an inhibitory role of IL-10-producing B cells in ALI and emphasized the importance of controlling inflammation during the initial stage of ALI.

Ultrafine particles in the airway aggravated experimental lung injury through impairment in Treg function.

Acute lung injury (ALI) is a life-threatening condition characterized by rapid-onset alveolar-capillary damage mediated by pathogenic proinflammatory immune responses. Since exposure to airway particulate matter (PM) could significantly change the inflammatory status of the individual, we investigated whether PM instillation in the airway could alter the course of ALI, using a murine model with experimental lung injury induced by intratracheal LPS challenge. We found that PM-treated mice presented significantly aggravated lung injury, which was characterized by further reductions in body weight, increased protein concentration in the bronchoalveolar lavage (BAL), and higher mortality rate, compared to control saline-treated mice. The PM-treated mice also presented elevated lung and systemic type 1 T helper cell (Th1) frequency as well as reduced lung regulatory T cell (Treg) frequency, which was associated with severity of lung injury. Further examinations revealed that the Treg function was impaired in PM-treated mice, characterized by significantly repressed transforming growth factor beta production. Adoptive transfer of functional Tregs from control mice to PM-treated mice significantly improved their prognosis after intratracheal LPS challenge. Together, these results demonstrated that first, PM in the airway aggravated lung injury; second, severity of lung injury was associated with T cell subset imbalance in PM-treated mice; and third, PM treatment induced quantitative as well as qualitative changes in the Tregs.

Upregulation of CD19⁺CD24(hi)CD38(hi) regulatory B cells is associated with a reduced risk of acute lung injury in elderly pneumonia patients.

Acute lung injury (ALI) is a common complication in elderly pneumonia patients who have a rapid progression, and is accompanied by a high mortality rate. Because the treatment options of ALI are limited to supportive care, identifying pneumonia patients who are at higher risk of ALI development is the emphasis of many studies. Here, we approach this problem from an immunological perspective by examining CD19(+)CD24(hi)CD38(hi) B cells, an important participant in acute and chronic inflammation. We find that elderly pneumonia patients have elevated CD19(+)CD24(hi)CD38(hi) B cell frequency compared to healthy individuals. This B cell population may express a higher level of IL-10, which has been was shown to suppress CD4(+) T cell-mediated proinflammatory cytokine interferon gamma (IFNg) and tumor necrosis factor alpha (TNFa) production, through an IL-10-dependent mechanism. We also observe that the frequency of CD19(+)CD24(hi)CD38(hi) B cell is positively correlated with the frequency of CD4(+)CD25(+)Foxp3(+)Tregs in peripheral blood. Moreover, consistent with CD19(+)CD24(hi)CD38(hi) B cell's anti-inflammatory role, we find that pneumonia patients who later developed ALI have reduced level of CD19(+)CD24(hi)CD38(hi) B cells. Together, our results demonstrated that CD19(+)CD24(hi)CD38(hi) B cells in pneumonia patients possess regulatory function in vivo, and are associated with a reduced ALI risk.

Regulatory B Cell Function Is Suppressed by Smoking and Obesity in H. pylori-Infected Subjects and Is Correlated with Elevated Risk of Gastric Cancer.

Helicobacter pylori infection occurs in more than half of the world's population and is the main cause for gastric cancer. A series of lifestyle and nutritional factors, such as tobacco smoking and obesity, have been found to elevate the risk for cancer development. In this study, we sought to determine the immunological aspects during H. pylori infection and gastric cancer development. We found that B cells from H. pylori-infected patients presented altered composition and function compared to uninfected patients. IL-10-expressing CD24+CD38+ B cells were upregulated in H. pylori-infected patients, contained potent regulatory activity in inhibiting T cell pro-inflammatory cytokine secretion, and responded directly to H. pylori antigen stimulation. Interestingly, in H. pylori-infected smoking subjects and obese subjects, the number of IL-10+ B cells and CD24+CD38+ B cells were reduced compared to H. pylori-infected asymptomatic subjects. Regulatory functions mediated by CD24+CD38+ B cells were also impaired. In addition, gastric cancer positive patients had reduced IL-10-producing B cell frequencies after H. pylori-stimulation. Altogether, these data suggest that in H. pylori-infection, CD24+CD38+ B cell is upregulated and plays a role in suppressing pro-inflammatory responses, possibly through IL-10 production, a feature that was not observed in smoking and obese patients.

CD86 polymorphism affects pneumonia-induced sepsis by decreasing gene expression in monocytes.

Sepsis, a clinical syndrome occurring in patients following infection or injury, is a leading cause of morbidity and mortality worldwide. CD86 (B7-2) is a costimulatory molecule on antigen-presenting cells and plays critical roles in immune responses. In the current study, we investigated the association of two CD86 polymorphisms, rs1129055G/A and rs17281995G/C, with susceptibility to pneumonia-induced sepsis and examined the effects of these two polymorphisms on gene expression in monocytes. CD86 rs1129055G/A and rs17281995G/C were identified in 192 pneumonia-induced septic patients and 201 healthy controls. Data showed that frequencies of the rs1129055GA and AA genotypes were significantly lower in patients than in controls (odds ratio [OR]=0.57, 95 % confidence interval [CI], 0.35-0.93, p=0.023, and OR=0.40, 95 % CI, 0.23-0.71, p=0.002). Interestingly, the other polymorphism, rs17281995G/C, revealed significantly increased numbers in pneumonia-induced sepsis compared to controls (OR=1.85, 95 % CI, 1.07-3.20, p=0.025). Further analyses about CD86 gene expression revealed that both messenger RNA (mRNA) and protein levels of CD86 were downregulated in monocytes from controls carrying rs17281995GC genotype than those carrying wild-type rs17281995GG genotype (p=0.022 and p=0013). These results suggest that polymorphisms in CD86 gene have diverse effects on the pathogenesis of pneumonia-induced sepsis, in which rs17281995G/C may increase the risk of the disease by interfering gene expression of CD86 in monocytes.

Regulatory T cells contribute to the recovery of acute lung injury by upregulating Tim-3.

Acute lung injury (ALI) is characterized by alveolar injury and uncontrolled inflammation. Mechanisms underlying pathogenesis of ALI are unknown. Regulatory T cells (Tregs), either natural or induced, suppress a variety of physiological and pathological immune responses. In the current study, we investigated whether Tregs were involved in the development of ALI. Proportion of CD4+CD25+FoxP3+ Tregs in the peripheral blood of 66 ALI patients and 30 healthy controls were examined by flow cytometry. Data showed that the percentage of Tregs in CD4+ T cells was significantly increased in patients than that in controls (10.8 versus 7.6%, P=0.003). Also, compared to those who died during the study, patients who survived presented significantly higher level of Tregs at the time of recruitment (P=0.041). Since Tim-3 is a negative regulatory molecule and can modulate the function of Tregs, we evaluated Tim-3 level on Tregs and identified upregulation of the molecule in patients than that in controls. Moreover, compared to those who died during the study, patients who survived showed 1.7-fold higher level of Tim-3 on Tregs at the time of recruitment (P<0.001). These results suggest that Tregs could affect the prognosis of ALI probably due to the upregulation of Tim-3.

Interleukin-21 polymorphism affects gene expression and is associated with risk of ischemic stroke.

There has been more and more evidence to confirm the essential role of inflammatory processes in the development of ischemic stroke. Interleukin-21 (IL-21), the most recently discovered CD132-dependent cytokine, plays a key role in regulating inflammation. The aim of the study was to understand the association between IL-21 polymorphisms and ischemic stroke, and the effects of these polymorphisms on gene expression. Two polymorphisms in IL-21, rs907715G/A and rs4833837A/G, were identified in 278 ischemic stroke patients and 282 healthy controls. Results showed that frequencies of rs907715GA and AA genotypes were significantly increased in cases than in controls (odd ratio (OR) = 1.49, 95% confidence interval (CI): 1.01-2.14, P = 0.042; OR = 2.21, 95% CI: 1.38-3.53, P = 0.001). Similarly, rs907715A allele revealed a positive association with the disease (OR = 1.52, P = 0.001). The rs4833837A/G polymorphism did not show any correlation with ischemic stroke. We further evaluated IL-21 messenger RNA (mRNA) and protein levels in peripheral blood mononuclear cells (PBMCs) from subjects carrying different polymorphism genotypes. Results revealed that subjects carrying polymorphic rs907715GA and AA genotypes had significantly higher IL-21 mRNA levels, whereas protein level was increased only in subjects with rs907715AA genotype. Serum level of IL-21 was also significantly elevated in subjects with rs907715AA genotype. These data suggest that IL-21 polymorphism is associated with increased susceptibility to ischemic stroke possibly by upregulating gene expression.

Toll-like receptor 3 genetic variants and susceptibility to hepatocellular carcinoma and HBV-related hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a highly aggressive cancer with few treatment options. Toll-like receptor 3 (TLR3) plays a key role in innate immunity and may affect the development of cancers. This study aimed to investigate whether TLR3 polymorphisms were associated with susceptibility to HCC. Two polymorphisms in the TLR3 gene, -976T/A and +1234C/T, were tested by polymerase chain reaction-restriction fragment length polymorphism in 466 HCC patients and 482 healthy controls. Results showed that the prevalence of +1234CT genotype and +1234TT genotype were significantly increased in the HCC cases than in controls (odds ratio [OR] =1.51; 95 % confidence interval [CI]; 1.22-1.93; p=0.004 and OR=3.19; 95 % CI, 1.82-5.39; p=1.99 × 10(-5), respectively). The -976T/A polymorphism did not reveal any differences between cases and controls. When analyzing the TLR3 +1234C/T polymorphism with different clinical parameters in HCC patients, the cases who were hepatitis B virus (HBV) carriers had higher number of +1234CT genotype and +1234T allele than those without HBV infection (p=0.032 and p=0.043). These data indicate that TLR3 +1234C/T polymorphism could be a novel risk factor for HCC, especially the HBV-related HCC.

A prospective randomized controlled trial to compare Pringle maneuver, hemihepatic vascular inflow occlusion, and main portal vein inflow occlusion in partial hepatectomy.

BACKGROUND: blood loss during liver resection and the need for perioperative blood transfusions have negative impact on perioperative morbidity, mortality, and long-term outcomes. METHODS: a randomized controlled trial was performed on patients undergoing liver resection comparing hemihepatic vascular inflow occlusion, main portal vein inflow occlusion, and Pringle maneuver. The primary endpoints were intraoperative blood loss and postoperative liver injury. The secondary outcomes were operating time, morbidity, and mortality. RESULTS: a total of 180 patients were randomized into 3 groups according to the technique used for inflow occlusion during hepatectomy: the hemihepatic vascular inflow occlusion group (n = 60), the main portal vein inflow occlusion group (n = 60), and the Pringle maneuver group (n = 60). Only 1 patient in the hemihepatic vascular occlusion group required conversion to the Pringle maneuver because of technical difficulty. The Pringle maneuver group showed a significantly shorter operating time. There were no significant differences between the 3 groups in intraoperative blood loss and perioperative mortality. The degree of postoperative liver injury and complication rates were significantly higher in the Pringle maneuver group, resulting in a significantly longer hospital stay. CONCLUSIONS: all 3 vascular inflow occlusion techniques were safe and efficacious in reducing blood loss. Patients subjected to hemihepatic vascular inflow occlusion, or main portal vein inflow occlusion responded better than those with Pringle maneuver in terms of earlier recovery of postoperative liver function. As hemihepatic vascular inflow occlusion was technically easier than main portal vein inflow occlusion, it is recommended.