Volume 135 · Issue 23 · 2022

Post-operative acute kidney injury (AKI) is one of the most common and serious complications after major surgery and is significantly associated with increased risks of morbidity and mortality. This meta-analysis was conducted to evaluate the effects of perioperative dexmedetomidine (Dex) administration on the occurrence of AKI and the outcomes of recovery after non-cardiac surgery.

The PubMed, Embase, Web of Science, and Cochrane Library databases were systematically searched for studies comparing the effects of Dex vs. placebo on kidney function after non-cardiac surgery, and a pooled fixed-effect meta-analysis of the included studies was performed. The primary outcome was the occurence of post-operative AKI. The secondary outcomes included the occurence of intra-operative hypotension and bradycardia, intensive care unit (ICU) admission, duration of ICU stay, and hospital length of stay (LOS).

Six studies, including four randomized controlled trials (RCTs) and two observational studies, with a total of 2586 patients were selected. Compared with placebo, Dex administration could not reduce the odds of post-operative AKI (odds ratio [OR], 0.44; 95% confidence interval (CI), 0.18-1.06; P= 0.07; I²= 0.00%, P= 0.72) in RCTs, but it showed a significant renoprotective effect (OR, 0.67; 95% CI, 0.48-0.95; P = 0.02; I² = 0.00%, P = 0.36) in observational studies. Besides, Dex administration significantly increased the odds of intra-operative bradycardia and shortened the duration of ICU stay. However, there was no significant difference in the odds of intra-operative hypotension, ICU admission, and hospital LOS.

This meta-analysis suggests that perioperative Dex administration does not reduce the risk of AKI after non-cardiac surgery. However, the quality of evidence for this result is low due to imprecision and inconsistent types of non-cardiac operations. Thus, large and high-quality RCTs are needed to verify the real effects of perioperative Dex administration on the occurrence of AKI and the outcomes of recovery after non-cardiac surgery.

Whether anesthetic depth affects postoperative outcomes remains controversial. This meta-analysis aimed to evaluate the effects of deep vs. light anesthesia on postoperative pain, cognitive function, recovery from anesthesia, complications, and mortality.

PubMed, EMBASE, and Cochrane CENTRAL databases were searched until January 2022 for randomized controlled trials comparing deep and light anesthesia in adult surgical patients. The co-primary outcomes were postoperative pain and delirium (assessed using the confusion assessment method). We conducted a meta-analysis using a random-effects model. We assessed publication bias using the Begg’s rank correlation test and Egger’s linear regression. We evaluated the evidence using the trial sequential analysis and Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. We conducted subgroup analyses for pain scores at different postoperative time points and delirium according to cardiac or non-cardiac surgery.

A total of 26 trials with 10,743 patients were included. Deep anesthesia compared with light anesthesia (a mean difference in bispectral index of -12 to -11) was associated with lower pain scores at rest at 0 to 1 h postoperatively (weighted mean difference = -0.72, 95% confidence interval [CI] = -1.25 to -0.18, P= 0.009; moderate-quality evidence) and an increased incidence of postoperative delirium (24.95% vs. 15.92%; risk ratio = 1.57, 95% CI = 1.28-1.91, P < 0.0001; high-quality evidence). No publication bias was detected. For the exploratory secondary outcomes, deep anesthesia was associated with prolonged postoperative recovery, without affecting neurocognitive outcomes, major complications, or mortality. In the subgroup analyses, the deep anesthesia group had lower pain scores at rest and on movement during 24 h postoperatively, without statistically significant subgroup differences, and deep anesthesia was associated with an increased incidence of delirium after non-cardiac and cardiac surgeries, without statistically significant subgroup differences.

Deep anesthesia reduced early postoperative pain but increased postoperative delirium. The current evidence does not support the use of deep anesthesia in clinical practice.

脓毒症是指宿主对感染的功能失调反应导致的多器官功能障碍。最重要的是，脓毒症患者的心肌损伤，即脓毒性心肌病（SIC），占医院死亡总数的1/3~1/2。SIC的发病机制在很大程度上仍不清楚，对此深入探讨对改善该患者群体的临床预后具有重要意义。

多器官功能障碍综合征（MODS）是一种以两个或多个系统或器官功能障碍为特征的临床综合征。这种内环境紊乱在严重创伤、休克或感染后24小时同时发生。MODS的病死率很高，从20%到100%不等。^[1]在严重创伤或感染后的MODS的发展中，多器官系统依次衰竭，涉及肺、肾、肝、心血管、中枢神经系统、胃肠、免疫和凝血系统。MODS致病因素复杂，主要有4种发病假说：（1）炎症失控假说，（2）缺血再灌注损伤假说，（3）胃肠道假说，（4）双相预激学说。虽然目前MODS的临床治疗方法如炎症因子抗体、高效抗凝剂、肾功能替代治疗等治疗方法不断改进，但其在MODS治疗中的有效性并不理想。因此，临床MODS治疗面临巨大挑战[图1].

Reperfusion therapy is fundamental for ST-segment elevation myocardial infarction (STEMI). However, the details of contemporary practice and factors associated with reperfusion therapy in China are largely unknown. Therefore, this study aimed to explore reperfusion practice and its associated factors among hospitalized patients with STEMI in China.

Patients with STEMI who were admitted to 159 tertiary hospitals from 30 provinces in China were included in the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome project from November 2014 to December 2019. The associations of the characteristics of patients and hospitals with reperfusion were examined using hierarchical logistic regression. The associations between therapies and in-hospital major adverse cardiovascular events were examined with a mixed effects Cox regression model.

Among the 59,447 patients, 37,485 (63.1%) underwent reperfusion, including 4556 (7.7%) receiving fibrinolysis and 32,929 (55.4%) receiving primary percutaneous coronary intervention (PCI). The reperfusion rate varied across geographical regions (48.0%-73.5%). The overall rate increased from 60.0% to 69.7% from 2014 to 2019, mainly due to an increase in primary PCI within 12 h of symptom onset. Timely PCI, but not fibrinolysis alone, was associated with a decreased risk of in-hospital major adverse cardiovascular events compared with no reperfusion, with an adjusted hazard ratio (95% confidence interval) of 0.64 (0.54,0.76) for primary PCI at <12 h, 0.53 (0.37,0.74) for primary PCI at 12 to 24 h, 0.46 (0.25,0.82) for the pharmaco-invasive strategy, and 0.79 (0.54,1.15) for fibrinolysis alone.

Nationwide quality improvement initiatives should be strengthened to increase the reperfusion rate and reduce inequality in China.

www.ClinicalTrials.gov, NCT02306616

The Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score was developed in 2013 to predict survival in heart failure (HF) patients. However, it has yet to be validated in a Chinese population. Our study aimed to investigate the ability of the score to predict 1-year mortality in a Chinese population.

Consecutive patients with HF were retrospectively selected from the inpatient electronic medical records of the cardiology department in a regional hospital in China. A total integer score was calculated for each enrolled patient based on the value of each risk factor in the MAGGIC scoring system. Each enrolled patient was followed for at least 1 year. The observational endpoint of this study was all-cause mortality. The predictive ability of the MAGGIC score was assessed by comparing observed and predicted mortality within 1 year.

Between January 2018 and December 2020, a total of 635 patients were included in the study: 57 (9.0%) of whom died within 1 year after discharge. The average age of all patients was 74.6 ± 11.2 years, 264 of them (41.6%) were male, and the average left ventricular ejection fraction was 50.7% ± 13.2%. The area under the receiver operating characteristic curve was 0.840 (95% confidence interval: 0.779, 0.901), which indicated a fair discriminatory ability of the score. The Hosmer-Lemeshow test result (χ² = 12.902, degree of freedom = 8, P = 0.115) indicated that the MAGGIC score had good calibration. The decision curve analysis showed that the MAGGIC score yielded a good clinical net benefit and net reduction in interventions.

This validation of the MAGGIC score showed that it has a good ability to predict 1-year mortality in Chinese patients with HF after discharge. Due to regional and inter-hospital differences, external validation studies need to be further confirmed in other centers.

Endovascular abdominal aortic aneurysm repair (EVAR) is the major treatment for abdominal aortic aneurysm (AAA); however, EVAR still carries a considerable risk of acute kidney injury (AKI). The present study aimed to investigate the risk factors for AKI after elective EVAR procedures.

This was a retrospective observational study. Eligible patients who underwent EVAR from September 2011 to March 2019 in West China Hospital were included. The primary outcome was the occurrence of AKI within two days after EVAR, which was defined by the Kidney Disease Improving Global Outcomes Clinical Practice Guideline. Demographics, comorbidities, medications, laboratory tests, anatomical parameters of AAA, and relative operative details were collected as variables. Univariable and multivariable logistic regression analyses were applied to identify the risk factors among variables, and covariate interactions were further assessed.

A total of 679 eligible patients were included. The incidence of postoperative AKI was 8.2% (56/679) in the whole cohort, and it was associated with a lower 5-year survival rate (63.5% vs. 80.9%; χ² = 4.10; P = 0.043). The multivariable logistic regression showed that chronic kidney disease (OR, 5.06; 95% CI: 1.43-17.95; P = 0.012), angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) (OR, 2.60; 95% CI: 1.17-5.76; P = 0.019), and short neck (OR, 2.85; 95% CI: 1.08-7.52; P = 0.035) were independent risk factors for postoperative AKI. In the covariate interaction analysis, the effect of ACEIs/ARBs use on postoperative AKI was similar across all subgroups (P > 0.05), thereby suggesting a robust effect of ACEIs/ARBs use in all patients undergoing elective endovascular abdominal aortic aneurysm repair.

Postoperative AKI was associated with lower survival rate, and the use of ACEIs/ARBs was the only adjustable independent risk factor. Clinicians should consider withdrawing ACEIs/ARBs in high-risk patients undergoing elective endovascular abdominal aortic aneurysm repair to prevent postoperative AKI.

Sepsis is a serious disease caused by infection. Aminophylline has anti-asthma and anti-inflammatory effects. We aimed to explore the safety and effect of aminophylline in sepsis.

We conducted a clinical randomized controlled trial involving 100 patients diagnosed with sepsis within 48 h after intensive care unit (ICU) admission in two sites. All patients were randomized in a 1:1 ratio to receive standard therapy with or without aminophylline. The primary clinical outcome was all-cause mortality at 28 days.

From September 27, 2018 to February 12, 2020, we screened 277 septic patients and eventually enrolled 100 patients, with 50 assigned to the aminophylline group and 50 to the usual-care group. At 28 days, 7 of 50 patients (14.0%) in the aminophylline group had died, compared with 16 of 50 (32.0%) in the usual-care group (P = 0.032). Cox regression showed that the aminophylline group had a lower hazard of death (hazard ratio = 0.312, 95% confidence interval: 0.129-0.753). Compared with the usual-care group, patients in the aminophylline group had a longer survival time (P = 0.039 by the log-rank test). The effects of aminophylline on vasopressor dose, oxygenation index, and sequential organ failure assessment score were time-dependent with treatment. There were no significant differences in total hospitalization days, ICU hospitalization days, and rates of serious adverse events (all P > 0.05). No adverse events were observed in the trial.

Aminophylline as an adjunct therapy could significantly reduce the risk of death and prolong the survival time of patients with sepsis.

ChiCTR.org.cn, ChiCTR1800019173.

Hepatopancreatoduodenectomy (HPD) has been considered the only curative treatment for metastatic cholangiocarcinoma and some locally advanced gallbladder cancers (GBCs). However, HPD has not yet been included in treatment guidelines as a standard surgical procedure in consideration of its morbidity and mortality rates. The aim of this study was to evaluate the safety and effectiveness of HPD in treating biliary malignancies.

The medical records of 57 patients with advanced biliary cancer undergoing HPD from January 2009 to December 2019 were retrospectively retrieved. A case-control analysis was conducted at our department. Patients with advanced GBC who underwent HPD (HPD-GBC group) were compared with a control group (None-HPD-GBC group). Baseline characteristics, preoperative treatments, tumor pathologic features, operative results, and prognosis were assessed.

Thirteen patients with cholangiocarcinoma and 44 patients with GBC underwent HPD at our department. Significant postoperative complications (grade III or greater) and postoperative pancreatic fistula were observed in 24 (42.1%) and 15 (26.3%) patients, respectively. One postoperative death occurred in the present study. Overall survival (OS) was longer in patients with advanced cholangiocarcinoma than in those with GBC (median survival time [MST], 31 months vs. 11 months; P < 0.001). In the subgroup analysis of patients with advanced GBC, multivariate analysis demonstrated that T4 stage tumors (P = 0.012), N2 tumors (P = 0.001), and positive margin status (P = 0.004) were independently associated with poorer OS. Patients with either one or more prognostic factors exhibited a shorter MST than patients without those prognostic factors (P < 0.001).

HPD could be performed with a relatively low mortality rate and an acceptable morbidity rate in an experienced high-volume center. For patients with advanced GBC without an N2 or T4 tumor, HPD can be a preferable treatment option.

Sepsis is a systemic inflammatory syndrome induced by several infectious agents. Multiple organs are affected by sepsis, including the liver, which plays an important role in metabolism and immune homeostasis. Fibroblast growth factors (FGFs) participate in several biological processes, although the role of FGF5 in sepsis is unclear.

In this study, lipopolysaccharide (LPS) was administrated to mice to establish a sepsis-induced liver injury. A similar in vitro study was conducted using L-02 hepatocytes. Western blot and immunohistochemistry staining were performed to evaluate the FGF5 expression level in liver tissues and cells. Inflammatory cell infiltrations, cleaved-caspase-3 expressions, reactive oxygen species and levels of inflammatory cytokines were detected by immunofluorescence, dihydroethidium staining, and reverse transcription quantitative polymerase chain reaction analysis, respectively. Flow cytometry was used to detect the apoptosis level of cells. In addition, ribonucleic acid (RNA)-sequencing was applied to explore the possible mechanism by which FGF5 exerted effects.

LPS administration caused FGF5 down-regulation in the mouse liver as well as in L-02 hepatocytes. Additionally, with FGF5 overexpression, liver injury and the level of hepatocyte apoptosis were ameliorated. Further, RNA sequencing performed in hepatocytes revealed the phosphoinositide-3-kinase/protein kinase B (PI3K/AKT) pathway as a possible pathway regulated by FGF5. This was supported using an inhibitor of the PI3K/AKT pathway, which abrogated the protective effect of FGF5 in LPS-induced hepatocyte injury.

The anti-apoptotic effect of FGF5 on hepatocytes suffering from LPS has been demonstrated and was dependent on the activation of the PI3K/AKT signaling pathway.

周围性肺部病变（PPLs）被肺实质包围，在内窥镜下看不见。常规支气管镜检查对PPLs的检出率较低。径向支气管内超声（R-EBUS）可以克服这些限制，因为它可以通过特征性超声信号定位外周支气管病变。

致编辑：当前指南建议在识别脓毒性休克患者后立即用≥30 mL/kg晶体液进行复苏。^[1]然而，与非协议复苏相比，对需要液体给药的脓毒症束的依从性未能提高死亡率。^[2]不适当的液体给药剂量，无论是不足还是过量，都会增加伤害的风险。据我们所知，很少有研究评估脓毒症标准液体复苏、液体超负荷和脱水治疗期间的血流动力学状态。此外，关于脓毒症中液体给药与血流动力学状态改变之间的关系，尤其是静脉回流的变化，知之甚少。最近的研究调查了平均全身充盈压（Pmsf）在指导血流动力学治疗中的有效性。平均全身充盈压（Pmsf）由血管充盈和血管张力两者决定，Pmsf和中心静脉压（CVP）之间的差代表血液返回心脏的驱动压力，从而代表心输出量（CO）。

致编辑：心肺复苏（CPR）指南，尤其是美国心脏协会（AHA）最新发布的2020年指南，都强调了高质量CPR的重要性。^[1]关于心脏骤停（CA）和CPR的研究近年来急剧增加，国际复苏指南也在修订和实施中。然而，院内心脏骤停（IHCA）的结局仍然很差，对IHCA后生存结局的预后因素缺乏了解，尤其是在中国。CA患者往往治疗不良，CA的发病率和死亡率逐年上升。^[2]本研究分析了CPR的效果，并探讨了影响成人IHCA术后生存结局的因素。

致编辑：院外和院内心脏骤停的常规心肺复苏（CCPR）的存活率在9%至20%之间。^[1]CCPR后如果没有恢复自主循环(ROSC)，恢复的机会很小。在这些患者中启动静脉动脉体外膜氧合可以提供足够的器官灌注，从而允许更长的器官活力，并为寻求纠正刺激病理事件的治疗提供时间，这被称为体外心肺复苏(ECPR)。^[2]治疗时间、ECPR相关并发症以及病因已被认为是ECPR患者生存的主要预测因素。^[3]ECPR在中国已经越来越多地开展，但关于ECPR应用的信息仍然未知。因此，我们对中国ECPR的使用情况进行了回顾性调查，包括患者选择、体外机械通气（ECMO）的启动和管理、患者结局，并比较了2017年和2020年的状况。

致编辑：甲基CpG结合域蛋白2（MBD2）属于组蛋白去乙酰化酶家族，通过抑制甲基化促进多基因表达，参与多种疾病的病理过程。细胞凋亡和炎症反应是导致多种免疫性疾病的主要机制。MBD2作为一种重要的甲基化蛋白阅读器，近年来已被证明在炎症反应中是不可或缺的。本文总结了目前对炎症MBD2生物学的认识，并通过总结目前对MBD2在炎症性疾病中的调节机制以及可能调节功能障碍的炎症途径的认识，为炎症机制的研究提供了额外的方向。截至2022年5月，PubMed、Embase和万方数据被搜索，没有语言限制，以查找MBD2在炎症途径、免疫细胞分化和巨噬细胞极化等方面的报告。鉴定的文献表明，MBD2可以在炎性疾病相关细胞中产生变化，并通过影响经典的炎症途径丝裂原活化蛋白激酶、免疫细胞T辅助（Th）细胞17（Th17）、Th1和Th2细胞以及巨噬细胞极化来调节炎症过程。因此，我们推断MBD2可能是炎症性疾病的有效治疗靶点，这应该有助于未来的研究。

致编辑：已知病原体相关分子模式和损伤相关分子模式（DAMPs）都会增强脓毒症期间的炎症和组织损伤水平。线粒体是DAMPs的主要来源，因为它们在脓毒症期间释放线粒体（mt）DNA片段。与细菌DNA类似，循环mtDNA可以激活信号通路并传播炎症。此前，普斯卡里奇等人^[1]在因脓毒症和脓毒性休克而到急诊科就诊的患者中，发现血浆mtDNA水平没有显著升高。然而，谢弗等人^[2]发现与对照组相比，脓毒症患者的血清mtDNA显著增加。此外，我们之前的研究表明，在合并急性肺损伤的脓毒症患者组中，入院后24小时内的循环mtDNA水平显著升高。^[3]因此，尚不清楚脓毒症期间mtDNA的变化是否具有临床相关性。本研究旨在确定重症监护室（ICU）入院24小时内的循环mtDNA是否可作为脓毒症早期诊断和预后的标志物。

致编辑：急性肾损伤（AKI）是重症监护病房（ICU）中急性胰腺炎的一种众所周知的严重并发症。发生AKI的急性胰腺炎患者的死亡率显著高于未发生AKI的患者。^[1]目前，急性胰腺炎患者AKI的诊断包括肾小球滤过率突然下降，表现为48 h~7天内血清肌酐升高或少尿。^[2]然而，当肌酐升高或尿量减少时，肾脏损害就会不可阻挡地发生。本研究旨在建立基于机器学习算法和传统逻辑回归方法的预测模型，仅使用入住ICU时常见收集的变量，并比较它们预测急性胰腺炎患者AKI发生的性能。

致编辑：淀粉样变性是由组织中不溶性β-折叠蛋白原纤维的细胞外沉积引起的，根据组成蛋白进行分类。淀粉样变性的病因可以追溯到30多种错误折叠的蛋白质，准确的淀粉样蛋白分型对于适当的治疗至关重要。^[1]病理诊断通过光学显微镜下刚果红（CR）阳性染色和电子显微镜下7-12nm分支原纤维来证实。一些淀粉样前体蛋白的进一步鉴定可以求助于免疫荧光（IF）和免疫化学（IHC）；然而，准确性在很大程度上取决于所选择的抗体。激光显微切割结合液相色谱-串联质谱（LMD/MS）可以在不受IF和IHC限制的情况下鉴定这些蛋白质，尽管需要精致的设备和熟练的专家。^[2]本研究旨在建立肾活检组织的LMD/MS分析，并将其与IHC的诊断敏感性进行比较。

致编辑：据估计，肝癌是第六大致死性肿瘤，约占所有癌症相关死亡的5.0%。^[1]主要由于乙型肝炎病毒的高感染率，肝癌在中国仍然是一个严重的健康问题，严重限制了人类预期寿命的延长。在中国，预计2022年肝癌新发病例和死亡人数将超过40万人。^[2]肝细胞癌（HCC）是肝癌的主要组织学类型，是一种复杂且高度异质性的疾病。由于缺乏早期症状，HCC患者通常在晚期才被确诊，从而失去手术切除或肝移植的机会。肿瘤复发和转移是限制外科治疗效率的主要障碍。探索HCC的分子机制，以开发有效的方法进行早期诊断，识别肿瘤复发转移高危患者是当务之急。

致编辑：沙眼衣原体（C.trachomatis）是专性细胞内病原体，通常由于宿主炎性免疫应答以及持续感染而导致慢性疾病和组织损伤的发展，^[1]其与Toll样受体(TLR)和髓样分化初级反应基因88(MyD88)介导的丝裂原活化蛋白激酶(MAPK)和细胞外调节蛋白激酶(ERK)的激活有关。^[2]此外，沙眼衣原体进化出了阻断宿主细胞凋亡的能力，涉及自噬和凋亡的相互作用。^[3]预防和治疗的新策略沙眼衣原体需要有效的感染。

致编辑：骨关节炎（OA）是一种突出的致残疾病，其特征在于进行性关节软骨损伤以及软骨下骨和关节的其他结构的退化，并且被列为导致全球残疾的第12大疾病。^[1]膝关节OA的病程相当长，可以单独或组合影响三个膝关节隔室（髌股关节[PFJ]、内侧胫股关节[MTFJ]和外侧胫股关节[LTFJ]），导致三个隔室中软骨损伤的发生有很大差异。^[2]我们的目的是确定与有OA风险的膝关节软骨损伤的不同三室轨迹相关的基线预测因素。