2022年 · 第135卷第23期

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.

Sepsis refers to multiple organ dysfunction caused by the host’s dysfunctional response to infection. Most importantly, myocardial injury in septic patients, that is, septic cardiomyopathy (SIC), accounts for 1/3 to 1/2 of the total number of hospital deaths. The pathogenesis of SIC remains largely unclear, for which in-depth exploration is of great significance to improve the clinical prognosis of this patient population.

Multiple organ dysfunction syndrome (MODS) is a clinical syndrome characterized by the dysfunction of two or more systems or organs. This internal environment disorder occurs simultaneously 24 h after severe trauma, shock, or infection. MODS has a high fatality rate ranging from 20% to 100%.^[1]In the development of MODS following severe trauma or infection, multiple organ system fail sequentially, involving the lungs, kidneys, liver, cardiovascular, central nervous system, gastrointestinal, immune, and the blood coagulation system. MODS has complex pathogenic factors, and there are four main pathogenesis hypotheses: (1) uncontrolled inflammation hypothesis, (2) ischemia-reperfusion injury, (3) the gastrointestinal hypothesis, and (4) the biphasic pre-excitation theory. Although the current clinical treatment methods of MODS, such as inflammatory factor antibodies, highly effective anti-coagulants, renal function replacement therapy, and other treatment methods, have been improved continuously, their effectiveness in MODS treatment is not ideal. Therefore, clinical MODS treatment is faced with great challenges [Figure 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.

Peripheral pulmonary lesions (PPLs) are surrounded by lung parenchyma and invisible under an endoscope. The detection rate of PPLs by routine bronchoscopy is low. Radial endobronchial ultrasound (R-EBUS) can overcome those limitations, as it can locate peripheral bronchial lesions through a characteristic ultrasound signal.

To the Editor: Current guidelines recommend resuscitation with ≥30 mL/kg of crystalloid fluid immediately upon recognition of septic shock patients.^[1]However, compliance with sepsis bundles requiring fluid administration to pre-specified goals has failed to improve mortality when compared with non-protocolized resuscitation.^[2]An inappropriate fluid administration dosage, whether insufficient or excessive, will increase the risk of harm. To our knowledge, few studies have been performed to evaluate the hemodynamic status during standard fluid resuscitation, fluid overload, and dehydration treatment in sepsis. Additionally, little is known about the relationship between fluid administration and altered hemodynamic states, especially changes in venous return, in sepsis. The usefulness of the mean systemic filling pressure (Pmsf) in guiding hemodynamic therapy has been investigated in recent studies. The mean systemic filling pressure (Pmsf) is determined by both vascular filling and vascular tone and the difference between Pmsf and central venous pressure (CVP) represents the driving pressure for the return of blood to the heart and thus for cardiac output (CO).

To the Editor:Cardiopulmonary resuscitation (CPR) guidelines, especially the latest 2020 guidelines issued by the American Heart Association (AHA), have emphasized the importance of high-quality CPR.^[1]The research on cardiac arrest (CA) and CPR has dramatically increased in recent years, and the international recovery guidelines are also being revised and implemented. However, the outcome of in-hospital cardiac arrest (IHCA) remains poor, and the understanding of the prognostic factors for survival outcome after IHCA is lacking, especially in China. Patients with CA are often poorly treated, and the incidence and mortality of CA are increasing yearly.^[2]This study analyzed the effects of CPR, and explored the factors that affect survival outcome after IHCA in adults.

To the Editor:The survival rate from conventional cardiopulmonary resuscitation (CCPR) of out-of-hospital and in-hospital cardiac arrest ranges from 9% to 20%.^[1]Without returning of spontaneous circulation (ROSC) after CCPR, the chance of recovery is very poor. Initiating venoarterial extracorporeal membrane oxygenation in those patients may provide adequate organ perfusion that allows for longer organ viability and permit time for therapies seeking to correct the inciting pathologic event, which is termed extracorporeal cardiopulmonary resuscitation (ECPR).^[2]Time to treatment, ECPR-related complications, as well as etiology, have been recognized as the main predictors of survival for ECPR patients.^[3]ECPR has been carried out more and more in China, but the information on ECPR application remains unknown. Therefore, we conducted a retrospective survey about the usage of ECPR in China, including patient selection, initiation and management of extracorporeal mechanical ventilation (ECMO), patient outcome, and compared the status during 2017 and 2020.

To the Editor:Methyl CpG binding domain protein 2 (MBD2) belongs to the histone deacetylase family, which promotes multi-gene expression by inhibiting methylation and participates in the pathological process of various diseases. Apoptosis and inflammatory response are the main mechanisms leading to a variety of immune diseases. MBD2, as an important methylation protein reader, has in recent years been shown to be indispensable in the inflammatory response. This paper summarizes the current understanding of inflammatory MBD2 biology and provides additional direction for the study of inflammatory mechanisms by summarizing the current understanding of the regulatory mechanisms of MBD2 in inflammatory diseases and the inflammatory pathways that may regulate dysfunction. PubMed, Embase, and Wanfang Data were searched up to May 2022 with no language restriction for reports on MBD2 in inflammatory pathways, immune cell differentiation, and macrophage polarization, among others. The identified literature showed that MBD2 can produce changes in the inflammatory disease-related cells, and regulate the inflammatory process by affecting the classical inflammatory pathway mitogen-activated protein kinase, the immune cells T helper (Th) cell 17 (Th17), Th1, and Th2 cells, and the macrophage polarization. Therefore, we infer that MBD2 may be an effective therapeutic target for inflammatory diseases, which should aid future research.

To the Editor:Both pathogen-associated molecular patterns and damage-associated molecular patterns (DAMPs) are known to enhance levels of inflammation and tissue injury during sepsis. Mitochondria are a major source of DAMPs because they release mitochondrial (mt) DNA fragments during sepsis. Similar to bacterial DNA, circulating mtDNA can activate signaling pathways and promulgate inflammation. Previously, Puskarich et al^[1]found no significant elevation in the levels of plasma mtDNA in patients presenting to the emergency department with sepsis and septic shock. However, Schäfer et al^[2]found that serum mtDNA significantly increased in septic patients compared with controls. Moreover, our previous study showed that circulating mtDNA levels within 24 h after admission were significantly increased in the group of septic patients with acute lung injury.^[3]Thus, it remains unclear whether changes in mtDNA during sepsis are of clinical relevance. This study aimed to determine whether circulating mtDNA within 24 h of intensive care unit (ICU) admission can be used as a marker for the early diagnosis and prognosis of sepsis.

To the Editor:Acute kidney injury (AKI) is a well-known and critical complication of acute pancreatitis in intensive care units (ICUs). Patients with acute pancreatitis who developed AKI had a significantly higher mortality than those without AKI.^[1]Currently, the diagnosis of AKI in acute pancreatitis patients includes a sudden decrease in glomerular filtration rate manifested by an increase in serum creatinine or oliguria within 48 h to 7 days.^[2]However, kidney damage occurs unstoppably when creatinine increases or urine output decreases. This study aimed to establish prediction models based on the machine learning algorithm and traditional logistic regression method only with commonly collected variables when admitted to the ICU, and we also compared their performance for predicting the occurrence of AKI in patients with acute pancreatitis.

To the Editor:Amyloidosis is caused by the extracellular deposition of insoluble beta-pleated protein fibrils in tissues and is classified according to the constituent proteins. The cause of amyloidosis can be traced to more than 30 kinds of malfolded proteins, and accurate amyloid typing is crucial for appropriate therapy.^[1]The pathological diagnosis is confirmed with positive Congo red (CR) staining under a light microscope and 7 to 12 nm branching fibrils under an electron microscope. Further identification of some amyloid precursor proteins can resort to immunofluorescence (IF) and immunochemistry (IHC); however, the accuracy depends on the selected antibodies to a large extent. Laser microdissection coupled with liquid chromatography-tandem mass spectrometry (LMD/MS) can identify these proteins without the restriction of IF and IHC, although exquisite equipment and skilled specialists are required.^[2]This study aimed to establish LMD/MS analysis of renal biopsy tissue and compare it with IHC on diagnostic sensitivity.

To the Editor:Liver cancer is estimated to be the sixth most lethal tumor, representing approximately 5.0% of all cancer-related deaths.^[1]Mainly due to the high rate of infection with hepatitis B virus, liver cancer remains a serious health concern in China, severely limiting the extension of human life expectancy. In China, the number of new cases and deaths from liver cancer is projected to exceed 400,000 in 2022.^[2]Hepatocellular carcinoma (HCC) is the major histological type of liver cancer and is a complex and highly heterogeneous disease. Due to the lack of early symptoms, patients with HCC are usually diagnosed at an advanced stage, thus losing the opportunity for surgical resection or liver transplantation. Tumor recurrence and metastasis are major bafflements that limit the efficiency of surgical therapeutics. It is urgent to explore the molecular mechanism of HCC to develop effective methods for early diagnosis and identify patients at high risk of tumor recurrence and metastasis.

To the Editor: Chlamydia trachomatis (C. trachomatis)is obligate intracellular pathogens, often resulting in development of chronic disease and tissue damage as a consequence of the host inflammatory immune response as well as persistent infections,^[1]which is associated with the activation of mitogen-activated protein kinase (MAPK) and extracellular regulated protein kinases (ERK) mediated by Toll-like receptors (TLRs) and myeloid differentiation primary response gene 88 (MyD88).^[2]Furthermore,C. trachomatishas evolved the ability to block the apoptosis of its host cells involving the interaction of autophagy and apoptosis.^[3]Novel strategies to prevent and treatC. trachomatisinfection effectively are needed.

To the Editor:Osteoarthritis (OA) is a prominent disabling disease characterized by progressive articular cartilage damage coupled with deterioration in the subchondral bone and other structures of the joint, and is ranked as the 12th highest disease contributing to global disability.^[1]The course of knee OA is considerably long and can affect three knee compartments (the patellofemoral joint [PFJ], medial tibiofemoral joint [MTFJ], and lateral tibiofemoral joint [LTFJ]) alone or in combination, resulting in a large variation in the occurrence of cartilage damage in the three compartments.^[2]We aimed to determine the baseline predictors associated with distinct tricompartmental trajectories of cartilage damage in knees at risk for OA.