Mechanism and clinical role of TIMP-2 and IGFBP-7 in cardiac surgery-associated acute kidney injury: A review.

Acute kidney injury (AKI) is a common postoperative complication, but there is still a lack of accurate biomarkers. Cardiac surgery-associated AKI is the most common cause of major-surgery-related AKI, and patients requiring renal replacement therapy have high mortality rates. Early diagnosis, intervention, and management are crucial for improving patient prognosis. However, diagnosing AKI based solely on changes in serum creatinine level and urine output is insufficient, as these changes often lag behind actual kidney damage, making early detection challenging. Biomarkers such as tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein-7 (IGFBP-7) have been found to be significant predictors of moderate-to-severe AKI when combined with urine content analysis. This article reviews the mechanism of biomarkers TIMP-2 and IGFBP-7 in AKI and provides a comprehensive overview of the clinical effects of TIMP-2 and IGFBP-7 in cardiac surgery-associated AKI, including prediction, diagnosis, and progression.

Concomitant tricuspid valve surgery in patients undergoing left ventricular assist device: a systematic review and meta-analysis.

INTRODUCTION: This study aims to investigate the effect of concomitant tricuspid valve surgery (TVS) during left ventricular assist device (LVAD) implantation due to the controversy over the clinical outcomes of concomitant TVS in patients undergoing LVAD. METHODS: A systematic literature search was performed in PubMed and EMbase from the inception to 1 August 2023. Studies comparing outcomes in adult patients undergoing concomitant TVS during LVAD implantation (TVS group) and those who did not (no-TVS group) were included. The primary outcomes were right heart failure (RHF), right ventricular assist device (RVAD) implantation, and early mortality. All meta-analyses were performed using random-effects models, and a two-tailed P <0.05 was considered significant. RESULTS: Twenty-one studies were included, and 16 of them were involved in the meta-analysis, with 660 patients in the TVS group and 1291 in the no-TVS group. Patients in the TVS group suffered from increased risks of RHF [risk ratios (RR)=1.31, 95% CI: 1.01-1.70, P =0.04; I2 =38%, pH =0.13), RVAD implantation (RR=1.56, 95% CI: 1.16-2.11, P =0.003; I2 =0%, pH =0.74), and early mortality (RR=1.61, 95% CI: 1.07-2.42, P =0.02; I2 =0%, pH =0.75). Besides, the increased risk of RHF holds true in patients with moderate to severe tricuspid regurgitation (RR=1.36, 95% CI: 1.04-1.78, P =0.02). TVS was associated with a prolonged cardiopulmonary bypass time. No significant differences in acute kidney injury, reoperation requirement, hospital length of stay, or ICU stay were observed. CONCLUSIONS: Concomitant TVS failed to show benefits in patients undergoing LVAD, and it was associated with increased risks of RHF, RVAD implantation, and early mortality.

Heart transplantation surgery in children and young adults with congenital heart disease.

BACKGROUND: Pediatric cardiac transplantation remains a surgical challenge as a variety of cardiac and vessel malformation are present in patients with congenital heart disease (CHD). Despite limited availability and acceptability of donor hearts, the number of heart transplantations remains on a stable level with improved survival and quality of life. OBSERVATION: As treatment options for CHD continue to improve and the chances of survival increase, more adult CHD patients are listed for transplantation. This review focuses on the clinical challenges and modified techniques of pediatric heart transplantations. CONCLUSION: Not only knowledge of the exact anatomy, but above all careful planning, interdisciplinary cooperation and surgical experience are prerequisites for surgical success.

Presence and impact of anemia in patients supported with left ventricular assist devices.

BACKGROUND: Data on anemia and its effects on patients supported with continuous-flow left ventricular assist devices (LVADs) are lacking. OBJECTIVES: This study sought to describe the presence of anemia over time and investigate its association with mortality, quality of life, exercise capacity, and adverse events in LVAD patients. METHODS: Adults receiving durable LVADs between 2008 and 2017 were identified from the INTERMACS database. The full cohort was stratified according to anemia severity (no anemia, mild, and moderate-severe). RESULTS: The analysis of 19,509 patients (females: 21.2%, age: 56.9 ± 12.9 years) showed that moderate-severe anemia affected 45.2% of patients at baseline, 33.5% of them at 6 months, and 32.3% in the fourth year after implantation. The presence of normal hemoglobin was 24.4% before surgery, 32.5% at 6 months, and 36.6% at 4 years after implantation. Multivariable linear mixed-effect regression revealed that the average hemoglobin over time was significantly lower (ß, -0.233, 95% confidence interval (CI): -0.282 to -0.185), and the reduction of hemoglobin over time was bigger (ß, -0.032 95% CI: -0.035 to -0.028) for LVAD nonsurvivors compared with LVAD survivors. Adjusted Cox regression showed that the severity of preimplant anemia was associated with higher mortality (HR, mild: 1.19; 95% CI: 1.05-1.35 and moderate-severe: 1.44; 95% CI: 1.28-1.62), with similar results in competing risk regression. Anemia progression during follow-up was associated with decreased Kansas City Cardiomyopathy Questionnaire scores and shorter 6-minute walk distances. CONCLUSIONS: In patients supported with LVADs, anemia is a frequent comorbidity, and deterioration over time is associated with poor prognosis.

Superior mesenteric artery syndrome following lung cancer surgery: A case report.

INTRODUCTION AND IMPORTANCE: Superior mesenteric artery syndrome (SMAS) is a rare medical condition resulting from vascular compression of the third part of the duodenum in the angle between the aorta and the superior mesenteric artery, leading to partial or complete intestinal obstruction and causing a series of symptoms. We now introduce a case of SMAS after lung cancer surgery, which was unique in that it was most likely caused by weight loss after surgery. CASE PRESENTATION: A 58-year-old male patient gradually developed severe nausea, vomiting, and weight loss after lung cancer surgery. A diagnosis of SMAS was made after the computed tomography of the abdomen was performed. The patient's symptoms were relieved after immediate placement of a nasojejunal nutrition tube for gastrointestinal decompression and enteral nutrition support. CLINICAL DISCUSSION: SMAS is rare and the symptoms are not specific, the clinical diagnosis of it is mostly confirmed by imaging. The presence of SMAS should be considered as a possibility when recurrent nausea and vomiting occur after lung surgery that excludes the above-mentioned causes. CONCLUSION: The signs and symptoms of SMAS are usually non-specific, which leads to misdiagnosis in all probability. SMAS should be considered when unexplained significant weight loss accompanied by recurrent nausea and vomiting happens to postoperative patients.

Characteristics and Outcome of Patients With a History of Cancer Undergoing Durable Left Ventricular Assist Device Implantation.

BACKGROUND: Patients with cancer (patients with a history of cancer) with advanced heart failure are increasing, but unlikely to be transplanted, and left ventricular assist device (LVAD) is an alternative strategy. This study investigates the characteristics and outcomes of patients with cancer undergoing durable LVAD. METHODS: Adult patients with a history of cancer who received LVADs were identified from INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) registry: 2008 and 2017. Characteristics and outcomes between patients with cancer and those without cancer were compared, and subgroup analyses of cancer therapy-induced cardiomyopathy (CCM) and non-CCM were also conducted. RESULTS: Overall, 1273 (6.5%) patients had a history of cancer, including 289 (22.7%) with CCM and 984 (77.3%) with non-CCM as the primary reason for heart failure. Patients with cancer had shorter median survival (3.72 versus 3.97 years, log-rank P=0.002), and multivariable Cox and competing risk regressions revealed that a history of cancer was associated with reduced survival (hazard ratio, 1.14 [95% CI, 1.04-1.26]; P=0.005; subdistribution hazard ratio, 1.24 [95% CI, 1.13-1.36]; P<0.001) and decreased incidence of heart transplantation. There was no significant difference in mortality between patients with CCM-induced heart failure and patients without cancer. Patients with cancer experienced an increased risk of bleeding, and age, INTERMACS profile, albumin, dialysis, and blood urea nitrogen were associated with mortality in these patients. CONCLUSIONS: A history of cancer is associated with mildly reduced survival, lower incidence of heart transplantation, and increased risk of bleeding after LVAD, whereas the survival in patients with cancer with CCM-induced heart failure is similar to those without cancer. LVAD implantation in patients with cancer is very well possible.

The prognostic value of advanced lung cancer inflammation index (ALI) in elderly patients with heart failure.

Purpose: The advanced lung cancer inflammation index (ALI) is a novel inflammatory and nutritional index that exerts prognostic value in various types of cancer. A previous study demonstrated that ALI at discharge could predict the prognosis in patients with acute decompensated heart failure (ADHF). However, the long-term prognostic value of ALI on admission in elderly heart failure (HF) inpatients remains unclear. Materials and methods: We retrospectively collected HF inpatients over 65-year-old who were hospitalized in our cardiology center during the whole year of 2015. ALI was calculated as body mass index (BMI) × serum albumin (Alb)/neutrophil-to-lymphocyte ratio (NLR). Patients were divided into two groups by the optimal cutoff value of ALI for predicting all-cause mortality using time-dependent receiver operating characteristic (ROC) curves. The Spearman rank correlation coefficient was computed to evaluate the correlation between ALI and the geriatric nutritional risk index (GNRI). Kaplan-Meier curves, Cox survival analyses, time-dependent ROC analyses, and net reclassification improvement (NRI) analyses were used to assess the prognostic effect of ALI on all-cause mortality and cardiovascular mortality. Results: Over a 28-month median follow-up, all-cause and cardiovascular mortality occurred in 192 (35.4%) and 132 (24.3%) out of 543 patients, respectively. The optimal cutoff value of ALI for predicting all-cause mortality at 2 years was 25.8. Spearman's correlation coefficient showed a moderate positive linear correlation between ALI and GNRI (r = 0.44, p < 0.001). The Kaplan-Meier analysis revealed that the cumulative incidences of both all-cause and cardiovascular mortalities were significantly higher in patients with lower ALI (log-rank test, all-cause mortality: p < 0.0001; cardiovascular mortality: p < 0.0001). The multivariate Cox proportional hazard analyses indicated that ALI was an independent predictor for both all-cause mortality (HR 0.550, 95% CI 0.349-0.867, p = 0.01) and cardiovascular mortality (HR 0.536, 95% CI 0.302-0.953, p = 0.034). Time-dependent ROC analyses showed that ALI was comparable to GNRI in predicting long-term all-cause mortality (AUC: ALI 0.625, GNRI 0.641, p = 0.976) and cardiovascular mortality (AUC: ALI 0.632, GNRI 0.626, p = 0.999) at 2 years. However, the estimated NRI indicated that the addition of ALI could not significantly improve risk stratification of base models for all-cause mortality (categorical NRI 4.9%, p = 0.433, continuous NRI 25%, p = 0.022) or cardiovascular mortality (categorical NRI 6.5%, p = 0.223, continuous NRI 27.5%, p = 0.029). Conclusion: Higher ALI was significantly associated with lower all-cause and cardiovascular mortalities in elderly HF patients. ALI on admission could be a competent nutrition-inflammation marker with independent predictive value for evaluating the long-term mortality of HF in elder population.

Tricuspid Valve Surgery in Patients Receiving Left Ventricular Assist Devices.

BACKGROUND: Tricuspid regurgitation (TR) is common and related to poor prognosis in patients after left ventricular assist device (LVAD) implantation. The concomitant tricuspid valve surgery (TVS) at the time of LVAD implantation on short and long-term outcomes are controversial in current evidence. METHODS: This is a single-center, observational, retrospective study. We enrolled patients with moderate-to-severe TR who received LVAD implantations from 2009 to 2020. Postoperative right ventricular failure (RVF), right ventricular assist device (RVAD) use, hospital mortality, new-onset renal replacement therapy (RRT), and acute kidney injury (AKI) were evaluated retrospectively. RESULTS: Sixty-eight patients were included, 36 with and 32 without concomitant TVS. Baseline characteristics did not differ between the two groups. Patients receiving TVS had significantly increased incidences of postoperative RVF (52.8 vs. 25.0%, p = 0.019), RVAD implantation (41.7 vs. 18.8%, p = 0.041), and new-onset RRT (22.2 vs. 0%, p = 0.004). No difference in the incidence of AKI and hospital mortality was detected. Besides, these associations remained consistent in patients who underwent LVAD implantation via median sternotomy. During a median follow-up of 2.76 years, Kaplan-Meier analysis and competing-risk analysis showed that TVS was not associated with better overall survival in patients after LVAD implantation compared with the no-TVS group. CONCLUSION: Our study suggests that concomitant TVS failed to show benefits in patients receiving LVAD implantation. Even worse, concomitant TVS is associated with significantly increased incidences of RVF, RVAD use, and new-onset of RRT. Considering the small sample size and short follow-up, these findings warrant further study.

Allicin attenuated hepatic ischemia/reperfusion injury in mice by regulating PPARγ-IRAK-M-TLR4 signal pathway.

Background: Hepatic ischemia/reperfusion (I/R) injury to the liver is a significant cause of morbidity and mortality following liver surgery, trauma, and hemorrhagic shock. It was reported that allicin, a type of garlic compound, had a protective effect against other hepatic diseases. Allicin's ability to protect against liver injury caused by ischemic reperfusion remains unknown. As a result, we conducted this study to determine allicin's effects and mechanism of action in hepatic I/R injury. Method: The liver I/R injury model was established by clamping the blood supply to the left and middle liver lobes. Three days prior to the hepatic I/R injury, different concentrations of allicin were gavaged. Then, hepatic function, histological changes, apoptosis markers, oxidative stress, and inflammatory cytokines were measured, and the molecular mechanisms were evaluated using western blot. Another separation experiment used IRAK-M knockout mice and peroxisome proliferator-activated receptor-gamma (PPARγ) inhibitor to deduce the molecular mechanisms. Results: Pretreatment with allicin prior to hepatic I/R injury reduced liver damage by inhibiting aminotransferase activity and alleviating liver injury. It significantly decreased cell apoptosis, interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) production, and hepatic oxidative stress. Furthermore, this study demonstrated that GW9662 (inhibitor of PPARγ) abrogated allicin's positive effect by inhibiting PPARγ expression while suppressing IRAK-M expression. Thus, the depletion of IRAK-M cannot influence the expression of PPARγ. The down-regulation of PPARγ-IRAK-M disabled the protection of allicin in I/R injury. Conclusion: Allicin protects against hepatic I/R injury via dose-dependent regulation of the PPARγ-IRAK-M-TLR4 signaling pathway, and it may be a potential drug in future clinical treatment.

Feasibility of Video-Assisted Thoracoscopic Surgery via Subxiphoid Approach in Anterior Mediastinal Surgery: A Meta-Analysis.

Background: Accumulating researches show potential advantages of video-assisted thoracoscopic surgery (VATS) via the subxiphoid approach, and this meta-analysis aims to investigate the efficacy and safety of the subxiphoid approach for anterior mediastinal surgery. Methods: Relevant studies were retrieved by searching Embase and PubMed databases (from the inception to October 1, 2021). Primary outcomes included postoperative pain, intraoperative blood loss, operation time, chest tube duration, and hospital length of stay. All meta-analyses were performed by using random-effects models. Results: Overall, 14 studies with 1,279 patients were included, with 504 patients undergoing anterior mediastinal surgery via subxiphoid approach and 775 via other approaches. The pooled results indicated that the subxiphoid approach was associated with reduced postoperative pain indicated by visual analog scale [weight mean difference (WMD): 24 h: -2.27, 95% CI, -2.88 to -1.65, p < 0.001; 48-72 h: -1.87, 95% CI, -2.53 to -1.20, p < 0.001; 7 days: -0.98, 95% CI, -1.35 to -0.61, p < 0.001], shortened duration of chest tube drainage (WMD: -0.56 days, 95% CI, -0.82 to -0.29, p < 0.001), shortened hospital length of stay (WMD: -1.46 days, 95% CI, -2.28 to -0.64, p < 0.001), and reduced intraoperative blood loss (WMD: -26.44 mL, 95% CI, -40.21 to -12.66, p < 0.001) by comparison with other approaches in anterior mediastinal surgery. Besides, it has no impact on operation time and the incidence of complications of transition to thoracotomy, postoperative pleural effusion, phrenic nerve palsy, and lung infection. Conclusions: Our study suggests that the subxiphoid approach is a feasible alternative approach and even can be a better option for anterior mediastinal surgery. Further, large-scale multicenter randomized controlled trials are needed to validate this finding.

Boyden's triad: the past, present and future.

OBJECTIVES: The B3 downwards-shifting malformation was first proposed by Boyden in 1950. Here, we report 14 cases of this malformation in the right lung and the first case of segmentectomy for this malformation. METHODS: All patients with pulmonary lesions underwent three-dimensional computed tomography bronchography and angiography (3D-CTBA) between January 2019 and January 2020, prior to surgery. A consecutive 2356 patients were included, and 14 cases of this malformation were identified; bronchovascular patterns were analysed in each patient. RESULTS: The incidence of this malformation was 0.6%. It was further divided into 3 types: over downwards-shift, partial downwards-shift and normal downwards-shift. The normal downwards-shift type was the most common (8/14), where B3 shifted downwards completely to merge with B4 + 5. In the partial downwards-shift (5/14), only part of the B3 shifted. In the over downwards-shift type (1/14), both B3 and B1b shifted downwards. A bifurcated right upper lobe （RUL) bronchus (B1 defective) was observed in 3 cases. The incidence of V1a, V1b, V2a, V2b, V2c, V3a, V3b and V3c was 100% (14/14). The incidence rates of A1, A3a and A3b were 100% (14/14). The incidence of A2 rec and A2 asc was 92.9% (13/14) and 71.4% (10/14), respectively. CONCLUSIONS: The B3 downwards-shifting malformation or 'Boyden's triad' is a rare anomaly. Anatomical exploration of this malformation is important for surgery.

Impact of cardiac fibrosis and collagens on right ventricular failure and acute kidney injury in patients after continuous-flow left ventricular assist devices.

OBJECTIVES: We aim to investigate the impact of cardiac fibrosis and collagens on right ventricular failure (RVF) and acute kidney injury (AKI) in patients receiving continuous flow left ventricular assist devices. METHODS: Heart tissues from 34 patients were obtained from continuous flow left ventricular assist device insertion sites and corresponding clinical data were collected. The participants were divided into 2 groups according to the extent of the cardiac fibrosis or collagens. RESULTS: Overall, 18 patients developed RVF with 14 receiving right ventricular assist device (RVAD), and 22 patients developed AKI with 12 needing new-onset renal replacement therapy. Higher collagen I (Col1) was significantly associated with increased incidences of RVF (76.5% vs 29.4%, P = 0.015), RVAD support (64.7% vs 17.6%, P = 0.013) and stage 3 AKI (58.8% vs 17.6%, P = 0.032), and patients with higher Col1 were more prone to renal replacement therapy (52.9% vs 17.6%, P = 0.071). Receiver operating characteristic curves showed that Col1 had good predictive effects on RVF [area under the curve (AUC) = 0.806, P = 0.002], RVAD support (AUC = 0.789, P = 0.005), stage 3 AKI (AUC = 0.740, P = 0.020) and renal replacement therapy (AUC = 0.731, P = 0.028) after continuous-flow left ventricular assist device. Moreover, patients with higher Col1 had significantly longer postoperative duration of mechanical ventilation, duration of intensive care unit stay and hospital length of stay (all P < 0.05). Cardiac fibrosis, collagen III (Col3) and Col1/Col3 shared similar results or trends with Col1. CONCLUSIONS: Cardiac fibrosis and related collagens in the apical left ventricular tissue are associated with increased risks of RVF, RVAD use and worse renal function. Further study is warranted owing to the small sample size.

Characteristics and prognosis of synchronous multiple primary lung cancer after surgical treatment: A systematic review and meta-analysis of current evidence.

BACKGROUND: This study aims to quantitatively summary the characteristics of synchronous multiple primary lung cancer (sMPLC), postoperative mortality, long-term prognosis, and prognostic effects of potential clinical parameters in patients with sMPLC after surgery. METHODS: PubMed and Embase databases were systematically searched to identify studies that explored the prognosis of patients with sMPLC after surgery. RESULTS: Fifty-two studies with 3486 participants were included, and clinical characteristics were quantitatively summarized. The pooled proportion of sMPLC in lung cancer was 2.0% (95%CI, 1.6%-2.5%) with an increasing trend over time, and postoperative mortality was 1.4% (95%CI, 0.5%-2.7%) with a decreasing trend over time. The 5-year survival rate was 44.9% (95%CI, 37.4%-52.6%) and all long-term survival rates showed increasing trends over time. Poor long-term prognosis was observed in both limited resection (HR = 1.357, 95%CI, 1.047-1.759, p = 0.0210) and pneumonectomy (HR = 2.643, 95%CI, 1.539-4.541, p = 0.0004) by comparison of anatomical resection. Other clinical parameters of age, gender, smoking status, FEV1, and lymph node metastasis significantly impacted the long-term prognosis (all p < 0.05). CONCLUSIONS: The proportion of sMPLC in lung cancer and 5-year survival rate are increasing, while postoperative mortality is decreasing trend over time. Lobectomy should be preferred, while pneumonectomy should be avoided for sMPLC. Age, gender, FEV1, smoking, tumor size, surgical methods, and lymph node status are prognostic factors for sMPLC. Considering the heterogeneity and publication bias, these findings should be treated with caution.

Open stented elephant trunk for complicated Stanford type B aortic dissection: a single-center experience.

BACKGROUND: Open stented elephant trunk (SET) or SET with left subclavian artery (LSCA) to left common carotid artery (LCCA) bypass is proven to a potentially alternative treatment for complicated Stanford type B aortic dissection (TBAD). In the current study, we reported our experience with ten consecutive TBAD patients who underwent open SET. METHODS: Patients with complicated TBAD underwent open SET from May 2016 to November 2018 in our institution were included. Patients' clinical data were obtained from the electronic medical record system, and long-term clinical outcomes were collected by telephone interviews or outpatient interviews. RESULTS: A total of ten patients with nine males and one female were included, and the average age was 47.3 (31-65) years. Increased D-dimer and fibrinogen degradation products were observed in all patients at admission, and two patients had renal insufficiency. The average postoperative mechanical ventilation time, length of stay in intensive care unit, and postoperative hospital length of stay were 46.9 (6.7-151.2) hours, 7.7 (4-17) days, and 15.7 (10-26) days. No postoperative death occurred. Acute kidney injury and other complications were observed, and they were recovered well when discharge. In long-term follow-up, computed tomography angiography indicated that aortas were completely well remodeled, and blood supply of the brachiocephalic trunks was normal without anastomotic complications. All patients lived well. CONCLUSION: SET or SET with subclavian artery correction shows satisfactory clinical outcomes, and it could be considered as an alternative treatment. Well-designed, large-scale studies with long-term follow-up are still needed.

miR-760 exerts an antioncogenic effect in esophageal squamous cell carcinoma by negatively driving fat metabolism via targeting c-Myc.

miR-760 is downregulated in various human tumors, and fat metabolism disorder correlates with tumor progression, especially anomalism of key fat metabolic enzymes that are positively modulated by c-Myc. The aim of our study is to elucidate the presumptive molecular mechanisms of miR-760-mediated esophageal squamous cell carcinoma (ESCC) cell function and to assess the therapeutic significance of miR-760 in ESCC patients. Quantitative real-time PCR (RT-qPCR) analysis indicated that miR-760 was significantly downexpressed in ESCC tissues and cell lines. Cell counting kit-8 (CCK-8) assay, colony formation assay, transwell assay, and flow cytometry denoted that induced ectopic overexpression of miR-760 dramatically inhibited ESCC cells proliferation, attenuated migration, and invasion facilitated apoptosis in vitro. Mechanistically, c-Myc predicted using bioinformatics was identified as a potential target gene of miR-760 by luciferase reporter assay. Furthermore, mRNA and protein expression levels of c-Myc and key fat metabolic enzymes were downregulated with miR-760 mimics. The above investigation results, responsible for the antineoplastic properties of miR-760 in ESCC, preliminarily highlighted that the hypothetical signal amongst miR-760, c-Myc, and key fat metabolic enzymes may develop a novel diagnostic marker, therapeutic target, and independent prognostic indicator.

Glycyrrhetinic acid pretreatment attenuates liver ischemia/reperfusion injury via inhibiting TLR4 signaling cascade in mice.

Glycyrrhetinic acid (GA), the main bioactive substances of glycyrrhiza uralensis Fisch, has been reported to exhibit hepatoprotective and anti-inflammatory properties. However, the effects and underlying mechanisms of GA in liver ischemia/reperfusion (I/R) injury remain elusive. In this study, mice were pretreated with GA (100 mg/kg) three times a day by gavage prior to I/R injury, and then hepatic histopathological damages, biochemical parameters and inflammatory molecules were evaluated. We found that mice performed with liver I/R showed a significantly increase in plasma aminotransferase (ALT), aspartate aminotransferase (AST), liver cell apoptosis and infiltration of neutrophils compared with the control group. GA pretreatment notably improved liver function, histopathology of liver tissues, and lowered liver cell apoptosis and infiltration of neutrophils. Besides, further analysis indicated that GA pretreatment reduced I/R-induced expression of extracellular HMGB1, inhibited activation of TLR4 and following phosphorylation of IRAK1, ERK, P38 and NF-κB, and attenuated TNF-α and IL-1ß production. These data suggested that GA protected against liver I/R injury through a HMGB1-TLR4 signaling pathway and it might be a promising drug for future clinical use in liver transplantation.

Annual case volume on mortality after coronary artery bypass grafting: a dose-response meta-analysis.

OBJECTIVES: This study evaluated the effect of both hospital and surgeon annual case volumes on patient mortality following coronary artery bypass grafting (CABG). METHODS: PubMed and Embase databases were searched for clinical studies on CABG. The outcome was mortality, including operative mortality, in-hospital mortality and 30-day mortality. RESULTS: Twenty-five studies involving 3 492 101 participants and 143 951 deaths were included for hospital volume, and 4 studies involving 108 356 participants and 2811 deaths were included for surgeon volume. The pooled estimate revealed that both hospital and surgeon annual case volumes were inversely associated with mortality in patients after CABG [odds ratio (OR) for hospital: 0.62, 95% confidence interval (CI) 0.56-0.69; P < 0.001; OR for surgeon: 0.51, 95% CI 0.31- 0.83; P < 0.001] with high heterogeneity (hospital: I2 = 90.6%, Pheterogeneity < 0.001; surgeon: I2 = 86.8%, Pheterogeneity < 0.001). The relationship remained consistent and robust in most subgroup and sensitivity analyses. Our meta-regression analysis of time suggested that the strength of the negative associations between volume and mortality for both hospitals and surgeons remained unattenuated over time even though the CABG mortality gradually decreased over time. The dose-response analysis suggested a non-linear relationship between both hospital and surgeon annual case volumes and mortality (both Pnon-linearity = 0.001). CONCLUSIONS: Both higher hospital and surgeon annual case volumes are associated with lower mortality in patients undergoing CABG, and the negative associations remain unattenuated over time. CLINICAL REGISTRATION NUMBER: The study was registered at PROSPERO as CRD42017067912.

Ferulic Acid Protected from Kidney Ischemia Reperfusion Injury in Mice: Possible Mechanism Through Increasing Adenosine Generation via HIF-1α.

Ferulic acid (FA), derived from fruits and vegetables, is well-known as a potent antioxidant of scavenging free radicals. However, the role and underlying mechanism of FA on kidney ischemia reperfusion (I/R) injury are limited. Here, we explored the effects of FA on kidney I/R injury. The kidney I/R injury models were carried out by clamping bilateral pedicles for 35 min followed by reperfusion for 24 h. Mice were orally pretreated with different doses of FA for three times 24 h before I/R. The renal function was assessed by serum creatine (Scr) and blood urea nitrogen (BUN). Kidney histology was examined by hematoxylin and eosin (HE) staining and terminal deoxynucleotidly transferased UTP nick-end labeling (TUNEL) assay. Proinflammatory cytokines, caspase-3 activity, adenosine generation, adenosine signaling molecules, and hypoxia inducible factor-1 alpha (HIF-1α) were also detected, respectively. The siHIF-1α adenovirus vectors were in vivo used to inhibit the expression of HIF-1α. The results showed that FA significantly attenuated kidney damage in renal I/R-operated mice as indicated by reducing levels of Scr and BUN, ameliorating renal pathological structural changes, and tubular cells apoptosis. Moreover, FA pretreatment inhibited I/R-induced renal proinflammatory cytokines and neutrophils recruitment. Interestingly, the levels of HIF-α, CD39, and CD73 mRNA and protein as well as adenosine production were all significantly increased after FA pretreatment in the kidney of I/R-performed mice, and inhibiting HIF-α expression using siRNA abolished this protection of FA on I/R-induced acute kidney injury as evidenced by more severe renal damage and reduced adenosine production. Our findings indicated that FA protected against kidney I/R injury by reducing apoptosis, alleviating inflammation, increasing adenosine generation, and upregulating CD39 and CD73 expression, which might be mediated by HIF-1α.

Inter-relationship among myasthenia gravis, WHO histology, and Masaoka clinical stage and effect on surgical methods in patients with thymoma: a retrospective cohort study.

BACKGROUND: The aim of study is to analyze the inter-relationship among WHO histology, myasthenia gravis (MG) and Masaoka stage and to assess the feasibility of thoracoscopic surgery in thymoma patients. METHODS: Data from 142 consecutive thymoma patients from January 2009 to March 2016 were retrospectively reviewed in our institution. Histological classification and clinical staging were assessed by WHO histology criteria and Masaoka stage. We investigated the clinical characteristics, inter-relationship among WHO histology, MG and Masaoka stage, and compared the feasibility and safety of thoracoscopic thymectomy by comparison of open thymectomy. RESULTS: Among 142 patients, the incidence of MG was 29.6%. Compared with A and AB-type thymomas, a higher prevalence of advance clinical stage was in B1 to C-type thymomas (37/63 vs. 9/43, P<0.001), and there was an increased trend of Masaoka stage from A to C-type thymomas (P<0.001). The incidence of MG was significantly higher in AB, B1 and B2-type thymomas than other type thymomas (23/63 vs. 6/44, P=0.009) and in early Masaoka clinical stage than advanced Masaoka clinical stage (29/80 vs. 12/59, P=0.042). Thoracoscopic surgery could significantly decrease blood loss in patients with (104.06±137.36 vs. 350.91±560.79 mL, P=0.001) or without MG (91.90±77.70 vs. 266.32±292.60 mL, P=0.02), with comparable complications. Additionally, thoracoscopic surgery could achieve an equal effect on the remission of MG with open surgery (7/11 vs. 10/14, P=1.000), and Masaoka stage was significantly associated with the remission of MG after thymectomy. CONCLUSIONS: Our study suggests that WHO histology, MG, and Masaoka stage interrelate with one another, and Masaoka stage is an important prognostic factor in remission of MG after thymectomy in thymoma patients. Thoracoscopic thymectomy could achieve an equal efficacy to open thymectomy and should be recommended as a routine surgery for patients with early Masaoka stage.