Single-cell and spatial transcriptome analyses reveal tertiary lymphoid structures linked to tumour progression and immunotherapy response in nasopharyngeal carcinoma.

Tertiary lymphoid structures are immune cell aggregates linked with cancer outcomes, but their interactions with tumour cell aggregates are unclear. Using nasopharyngeal carcinoma as a model, here we analyse single-cell transcriptomes of 343,829 cells from 77 biopsy and blood samples and spatially-resolved transcriptomes of 31,316 spots from 15 tumours to decipher their components and interactions with tumour cell aggregates. We identify essential cell populations in tertiary lymphoid structure, including CXCL13+ cancer-associated fibroblasts, stem-like CXCL13+CD8+ T cells, and B and T follicular helper cells. Our study shows that germinal centre reaction matures plasma cells. These plasma cells intersperse with tumour cell aggregates, promoting apoptosis of EBV-related malignant cells and enhancing immunotherapy response. CXCL13+ cancer-associated fibroblasts promote B cell adhesion and antibody production, activating CXCL13+CD8+ T cells that become exhausted in tumour cell aggregates. Tertiary lymphoid structure-related cell signatures correlate with prognosis and PD-1 blockade response, offering insights for therapeutic strategies in cancers.

Pd-Catalyzed cascade Heck cyclization/carbonylation of indoles with aryl formates: enantioselective construction of indolo[2,1-a]isoquinolines.

An efficient palladium-catalyzed cascade cyclization/carbonylation of indoles with aryl formates to access ester-functionalized indolo[2,1-a]isoquinoline scaffolds has been developed. In addition, an asymmetric variant is also achieved using a chiral phosphine ligand, affording the indolo[2,1-a]isoquinoline products in good yields and enantioselectivities.

Effects of a single subanesthetic dose of esketamine on postoperative subthreshold depressive symptoms in patients undergoing unilateral modified radical mastectomy: a randomised, controlled, double-blind trial.

BACKGROUND: Breast cancer is the most common malignant tumor in females worldwide. During disease development, breast cancer patients suffer anxious and depressed, which may lead to worse quality of life or even higher mortality. Esketamine has been regarded as an antidepressant in breast cancer patients with mild or moderate depression. Here, we wonder whether the administration of esketamine could reduce the postoperative depressive symptom score of breast cancer patients who have no preoperative depression. METHODS: A total of 64 patients treated with unilateral modified radical mastectomy were randomly divided into an experimental group (esketamine group, Group E) and a control group (Group C), with 32 cases in each one. After anesthesia induction, Group C received 0.2 ml/kg of normal saline intravenously and Group E was administered 0.2 mg/kg intravenous esketamine. The primary outcome was the Patient Health Questionnaire-9 (PHQ-9) scores. The secondary outcomes included the Visual Analogue Scale (VAS) scores for pain, inflammatory markers, perioperative-related indicators, and the incidence of postoperative delirium, nausea and vomiting. RESULTS: The PHQ-9 score on postoperative day (POD) 1 in Group E declined from the preoperative level, while the score in Group C was higher than before, and the former was far lower than the latter (P = 0.047). There is no statistically significant difference in PHQ-9 scores between Group E and Group C on POD 3, 7, and 30. Moreover, the postoperative leukocyte level of Group E was higher than that of Group C, and the difference was statistically significant (P = 0.030). CONCLUSIONS: A single subanesthetic dose of esketamine can result in lower postoperative score on subthreshold depressive symptoms compared to the Group C on POD 1, without increasing the occurrence of postoperative adverse reactions. TRIAL REGISTRATION: Registration number: Chinese Clinical Trial Registry ChiCTR2200057028. Date of registration: 26/02/2022.

AKAP150 from nucleus accumbens dopamine D1 and D2 receptor-expressing medium spiny neurons regulates morphine withdrawal.

Dopamine D1 receptor-expressing medium spiny neurons (D1R-MSNs) and dopamine D2 receptor-expressing MSNs (D2R-MSNs) in nucleus accumbens (NAc) have been demonstrated to show different effects on reward and memory of abstinence. A-kinase anchoring protein 150 (AKAP150) expression in NAc is significantly upregulated and contributes to the morphine withdrawal behavior. However, the underlying mechanism of AKAP150 under opioid withdrawal remains unclear. In this study, AKAP150 expression in NAc is upregulated in naloxone-precipitated morphine withdrawal model, and knockdown of AKAP150 alleviates morphine withdrawal somatic signs and improves the performance of conditioned place aversion (CPA) test. AKAP150 in NAc D1R-MSNs is related to modulation of the performance of morphine withdrawal CPA test, while AKAP150 in NAc D2R-MSNs is relevant to the severity of somatic responses. Our results suggest that AKAP150 from D1R-MSNs or D2R-MSNs in NAc contributes to the developmental process of morphine withdrawal but plays different roles in aspects of behavior or psychology.

Construction of Conjugated 1,3-Enynes via Pd-Catalyzed Cascade Alkynylation of Aryl Phenol-Tethered Alkynes with Alkynyl Bromides.

An efficient Pd-catalyzed cascade alkynylation of aryl phenol-tethered alkynes with alkynyl bromides is described. This protocol could provide various conjugated 1,3-enynes possessing a polysubstituted spirocyclohexadienone, as well as an all-carbon tetrasubstituted alkene moiety. The products could also undergo ring-expansion and cyclization transformations under different conditions to convert to diverse fused cyclic scaffolds.

M1A and m7G modification-related genes are potential biomarkers for survival prognosis and for deciphering the tumor immune microenvironment in esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is the most common esophageal malignancy, and RNA methylation has been reported to be involved in the tumorigenesis of ESCC. However, no study has explored methylation modifications in m1A and m7G as prognostic markers for survival prediction in ESCC. METHODS: Public gene-expression data and clinical annotation of 254 patients obtained from The Cancer Genome Atlas and the Gene Expression Omnibus databases were analyzed to identify potential consensus clusters of m1A and m7G modification-related genes. The RNA-seq of 20 patients in Sun Yat-Sen University Cancer Center was used as the validation set. Following screening for relevant differentially expressed genes (DEGs) and enrichment pathways were elucidated. DEGs were used to construct risk models using the randomForest algorithm, and the prognostic role of the models was assessed by applying Kaplan-Meier analysis. Extent of immune cell infiltration, drug resistance, and response to cancer treatment among different clusters and risk groups were also evaluated. RESULTS: Consensus clustering analysis based on m1A and m7G modification patterns revealed three potential clusters. In total, 212 RNA methylation-related DEGs were identified. The methylation-associated signature consisting of 6 genes was then constructed to calculate methylation-related score (MRScore) and patients were dived into MRScore-high and MRScore-low groups. This signature has satisfied prognostic value for survival of ESCC (AUC = 0.66, 0.67, 0.64 for 2-, 3-, 4- year OS), and has satisfied performance in the validation SYSUCC cohort (AUC = 0.66 for 2- and 3-year OS). Significant correlation between m1A and m7G modification-related genes and immune cell infiltration, and drug resistance was also observed. CONCLUSIONS: Transcriptomic prognostic signatures based on m1A and m7G modification-related genes are closely associated with immune cell infiltration in ESCC patients and have important correlations with the therapeutic sensitivity of multiple chemotherapeutic agents.

The YTHDF1-TRAF6 pathway regulates the neuroinflammatory response and contributes to morphine tolerance and hyperalgesia in the periaqueductal gray.

Long-term use of opioids such as morphine has negative side effects, such as morphine analgesic tolerance and morphine-induced hyperalgesia (MIH). These side effects limit the clinical use and analgesic efficacy of morphine. Elucidation of the mechanisms and identification of feasible and effective methods or treatment targets to solve this clinical phenomenon are important. Here, we discovered that YTHDF1 and TNF receptor-associated factor 6 (TRAF6) are crucial for morphine analgesic tolerance and MIH. The m6A reader YTHDF1 positively regulated the translation of TRAF6 mRNA, and chronic morphine treatments enhanced the m6A modification of TRAF6 mRNA. TRAF6 protein expression was drastically reduced by YTHDF1 knockdown, although TRAF6 mRNA levels were unaffected. By reducing inflammatory markers such as IL-1ß, IL-6, TNF-α and NF-κB, targeted reduction of YTHDF1 or suppression of TRAF6 activity in ventrolateral periaqueductal gray (vlPAG) slows the development of morphine analgesic tolerance and MIH. Our findings provide new insights into the mechanism of morphine analgesic tolerance and MIH indicating that YTHDF1 regulates inflammatory factors such as IL-1ß, IL-6, TNF-α and NF-κB by enhancing TRAF6 protein expression.

Pd-Catalyzed Cascade Intramolecular Heck Cyclization/Dearomatization of Indoles for the Construction of Two All-Carbon Quaternary Centers.

A facile Pd-catalyzed cascade of intramolecular Heck cyclization/alkylpalladium activated dearomatization of aryl alkyne-tethered indole is described. In this single step two nonadjacent all-carbon quaternary centers, two nitrogen-containing heterocycles, and three C(sp2)-C(sp3) bonds are efficiently furnished. These products could also undergo 5-to-6 ring migration-expansion reaction under Brønsted-acid conditions to transform into the benzo[c]carbazole skeletons.

Association of proton pump inhibitor use with survival outcomes in cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis.

Background: Proton pump inhibitors (PPIs) have been shown to regulate the gut microbiome and affect the response to immune checkpoint inhibitors (ICIs). Contradictory results on survival have been observed in patients concomitantly treated with ICIs and PPIs. We performed a systematic review and meta-analysis to determine the association between PPI use and survival outcomes in ICI-treated cancer patients. Methods: EMBASE, MEDLINE/PubMed, Cochrane Library databases, and major oncology conference proceedings were searched. Studies comparing overall survival (OS) and progression-free survival (PFS) between PPI-treated and PPI-free groups of ICI-treated cancer patients were included. Data regarding study and patient characteristics, ICI and PPI treatments, and survival outcomes were extracted. Hazard ratios (HRs) with 95% confidence interval (CI) were pooled using random effects models. Subgroup meta-analyses and meta-regressions were performed to explore possible factors of heterogeneity among the studies. Results: A total of 33 studies were included, comprising 7383 ICI- and PPI-treated patients and 8574 ICI-treated and PPI-free patients. The pooled HR was 1.31 (95% CI, 1.19-1.44; p < 0.001) for OS and 1.30 (95% CI, 1.17-1.46; p < 0.001) for PFS, indicating a significant negative association between PPI use and survival in ICI-treated patients. Subgroup meta-analyses by factors including cancer type, ICI type, and time window of PPI use revealed that ICI and PPI use impacted survival in patients with non-small cell lung or urothelial cancer, patients treated with anti-PD-1/PD-L1 antibodies, and patients receiving PPI as baseline treatment or 60 days before ICI treatment initiation. Conclusions: PPI use in patients treated with ICIs was associated with shorter OS and PFS, especially in several specific subgroups of cancer patients. PPIs should be strictly controlled and appear to not impact survival if given temporarily after ICI initiation. These observations could provide the basis for clinical guidelines for concomitant PPI and ICI use.

Pd-Catalyzed C-H Functionalization of Indole-Containing Alkene-Tethered Aryl Halides with Alkynes To Construct Indole Alkaloid Scaffolds.

A convenient and straightforward approach for the construction of indole alkaloid scaffolds from indole-containing alkene-tethered aryl halides and alkynes through a sequential C-H activation, five-membered palladacycle formation, and alkyne insertion process has been described. The approach provides a series of indole alkaloid compounds in moderate to excellent yields with good functional tolerance.

Development and validation of a prognostic model and gene co-expression networks for breast carcinoma based on scRNA-seq and bulk-seq data.

Background: Breast carcinoma is the most common malignancy among women worldwide. It is characterized by a complex tumor microenvironment (TME), in which there is an intricate combination of different types of cells, which can cause confusion when screening tumor-cell-related signatures or constructing a gene co-expression network. The recent emergence of single-cell RNA sequencing (scRNA-seq) is an effective method for studying the changing omics of cells in complex TMEs. Methods: The Dysregulated genes of malignant epithelial cells was screened by performing a comprehensive analysis of the public scRNA-seq data of 58 samples. Co-expression and Gene Set Enrichment Analysis (GSEA) analysis were performed based on scRNA-seq data of malignant cells to illustrate the potential function of these dysregulated genes. Iterative LASSO-Cox was used to perform a second-round screening among these dysregulated genes for constructing risk group. Finally, a breast cancer prognosis prediction model was constructed based on risk grouping and other clinical characteristics. Results: Our results indicated a transcriptional signature of 1,262 genes for malignant breast cancer epithelial cells. To estimate the function of these genes in breast cancer, we also constructed a co-expression network of these dysregulated genes at single-cell resolution, and further validated the results using more than 300 published transcriptomics datasets and 31 Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) screening datasets. Moreover, we developed a reliable predictive model based on the scRNA-seq and bulk-seq datasets. Conclusions: Our findings provide insights into the transcriptomics and gene co-expression networks during breast carcinoma progression and suggest potential candidate biomarkers and therapeutic targets for the treatment of breast carcinoma. Our results are available via a web app (https://prognosticpredictor.shinyapps.io/GCNBC/).

Dexmedetomidine vs. lidocaine for postoperative analgesia in pediatric patients undergoing craniotomy: a protocol for a prospective, randomized, double-blinded, placebo-controlled trial.

BACKGROUND: Postoperative pain is a common problem that occurs in pediatric patients following neurosurgery which may lead to severe complications. Dexmedetomidine is a commonly used adjuvant medicine in craniotomy owing to its sedative, amnestic, analgesic, and neuroprotective properties. Besides, studies suggest that lidocaine has similar effects on sedation, analgesia, and neuroprotection. Both two adjuvants can reduce postoperative pain after neurosurgery in adults. However, it is still unknown whether dexmedetomidine or lidocaine can reduce postoperative pain in children undergoing craniotomy, and if yes, which is a better medicine choice. Therefore, we aimed to compare the effect of dexmedetomidine vs. lidocaine on postoperative pain in pediatric patients after craniotomy. METHODS/DESIGN: We will perform a randomized (1:1:1), double-blind, placebo-controlled, single-center trial. Children aged 1-12 years scheduled for craniotomy will be eligible for inclusion. The 255 recruited participants will be stratified by age in two strata (1-6 years and 7-12 years), and then each stratum will be equally randomized to three groups: group D (infusion of dexmedetomidine [intervention group]), group L (infusion of lidocaine [intervention group]), and group C (infusion of normal saline [control group]). Patients will be followed up at 1 h, 2 h, 4 h, 24 h, and 48 h after surgery. The primary outcome will be total sufentanil consumption within 24 h after surgery. DISCUSSION: In this clinical trial, we expect to clarify and compare the postoperative analgesic effect of dexmedetomidine vs. lidocaine infusion on pediatric patients undergoing craniotomy. We believe that the results of this trial will provide more choices for postoperative analgesia for the pediatric population. TRIAL REGISTRATION: Chinese ClinicalTrials.gov ChiCTR1800019411 . Registered on 10 November 2018.

Palladium-Catalyzed Cascade Allylative Dicarbofunctionalization of Aryl Phenol-Tethered Alkynes with Allyl Iodides: Synthesis of Skipped Dienes.

A palladium-catalyzed cascade allylative dicarbofunctionalization of aryl phenol-tethered alkynes with allyl iodides is described. A series of polysubstituted spirocyclo-containing skipped dienes with an all-carbon tetrasubstituted alkene unit are synthesized through this convenient process. The cascade reaction proceeds selectively through dearomative C-allylation instead of O-allylation of aryl phenols.

Oral maintenance therapy using apatinib combined with S-1/capecitabine for esophageal squamous cell carcinoma with residual disease after definitive chemoradiotherapy.

BACKGROUND: A substantial number of patients with esophageal squamous cell carcinoma (ESCC) do not achieve complete remission after definitive concurrent chemoradiotherapy (dCRT). We performed this retrospective study to evaluate the efficacy and safety of apatinib combined with S-1/capecitabine as the oral maintenance therapy for these patients. METHODS: Thirty-nine ESCC patients with residual disease after dCRT were included. Patients were treated with apatinib combined with S-1 /capecitabine after dCRT. Efficacy, toxicity, and survival were analyzed. RESULTS: Of the 39 patients, 5 (12.8%) achieved a partial response and 29 (74.4%) achieved stable disease, yielding a disease control rate of 87.2%. The median progression-free survival (PFS) and overall survival (OS) were 27.5 (95%CI: 14.9 - 40.1) and 38.1 (95%CI: 31.3 - 44.8) months. Most frequent adverse events were of grade 1 to 2. Multivariate analysis revealed the occurrence of any adverse events (HR = 0.274, 95%[CI] = 0.119 - 0.630) correlated to better PFS and occurrence of proteinuria (HR = 0.108, 95%[CI] = 0.025 - 0.456) predicted better OS. CONCLUSION: The oral combination therapy consisting of apatinib and S-1/capecitabine showed a tolerable toxicity profile and achieved satisfactory disease control in ESCC patients with residual disease after dCRT.

Tumour heterogeneity and intercellular networks of nasopharyngeal carcinoma at single cell resolution.

The heterogeneous nature of tumour microenvironment (TME) underlying diverse treatment responses remains unclear in nasopharyngeal carcinoma (NPC). Here, we profile 176,447 cells from 10 NPC tumour-blood pairs, using single-cell transcriptome coupled with T cell receptor sequencing. Our analyses reveal 53 cell subtypes, including tumour-infiltrating CD8+ T, regulatory T (Treg), and dendritic cells (DCs), as well as malignant cells with different Epstein-Barr virus infection status. Trajectory analyses reveal exhausted CD8+ T and immune-suppressive TNFRSF4+ Treg cells in tumours might derive from peripheral CX3CR1+CD8+ T and naïve Treg cells, respectively. Moreover, we identify immune-regulatory and tolerogenic LAMP3+ DCs. Noteworthily, we observe intensive inter-cell interactions among LAMP3+ DCs, Treg, exhausted CD8+ T, and malignant cells, suggesting potential cross-talks to foster an immune-suppressive niche for the TME. Collectively, our study uncovers the heterogeneity and interacting molecules of the TME in NPC at single-cell resolution, which provide insights into the mechanisms underlying NPC progression and the development of precise therapies for NPC.

Non-Coding RNAs in IGF-1R Signaling Regulation: The Underlying Pathophysiological Link between Diabetes and Cancer.

The intricate molecular network shared between diabetes mellitus (DM) and cancer has been broadly understood. DM has been associated with several hormone-dependent malignancies, including breast, pancreatic, and colorectal cancer (CRC). Insulin resistance, hyperglycemia, and inflammation are the main pathophysiological mechanisms linking DM to cancer. Non-coding RNAs (ncRNAs), particularly microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), are widely appreciated as pervasive regulators of gene expression, governing the evolution of metabolic disorders, including DM and cancer. The ways ncRNAs affect the development of DM complicated with cancer have only started to be revealed in recent years. Insulin-like growth factor 1 receptor (IGF-1R) signaling is a master regulator of pathophysiological processes directing DM and cancer. In this review, we briefly summarize a number of well-known miRNAs and lncRNAs that regulate the IGF-1R in DM and cancer, respectively, and further discuss the potential underlying molecular pathogenesis of this disease association.

Postoperative pulmonary complications and hospital stay after lung resection surgery: A meta-analysis comparing nonintubated and intubated anesthesia.

BACKGROUND: Since postoperative pulmonary complications are one of the main causes of morbidity and mortality in patients undergoing lung resection surgery, we performed a meta-analysis to compare the incidence of postoperative pulmonary complications and hospital death, and the length of hospital stay in patients who received nonintubated or intubated anesthesia during thoracoscopic surgery for lung resection and further explore the tricks in nonintubated anesthesia. METHODS: PubMed, Embase, and Cochrane Library were searched from inception to September 2017. We included eligible research comparing nonintubated anesthesia with intubated anesthesia in thoracoscopic surgery for lung resection. The primary outcomes involved postoperative pulmonary complications, hospital death, and hospital stay. The rates and causes of conversion from nonintubated anesthesia to intubated anesthesia were also analyzed. RESULTS: After screening through 754 potentially relevant articles, we included 3 randomized controlled trials and 7 observational studies with 1138 patients. There was no perioperative mortality in 2 groups. The nonintubated group revealed comparable postoperative pulmonary complications (OR = 0.57; P = .07; P for heterogeneity = .49, I = 0%) and shorter hospital stay (WMD = -1.10; P < .00001; P for heterogeneity = .84, I = 0%) in overall findings with little heterogeneity. CONCLUSION: Nonintubated anesthesia in thoracoscopic surgery for lung resection shortened the length of hospital stay compared with intubated anesthesia. However, the incidence of postoperative pulmonary complications was comparable between nonintubated and intubated group. Given the potential perioperative emergencies, such as persistent hypoxemia, carbon dioxide retention, or extensive pleural adhesions, nonintubated anesthesia in lung resection surgery requires extra vigilance to ensure the safety of the patients and the success of the surgery. Powerful randomized controlled trials in the future are essential to provide more certainty and address long-term effectiveness. Only when anesthesiologists and surgeons make efforts together can better clinical outcomes in lung resection surgery be achieved.

Ventilation during cardiopulmonary bypass for prevention of respiratory insufficiency: A meta-analysis of randomized controlled trials.

BACKGROUND: Cardiopulmonary bypass (CPB) is necessary for most cardiac surgery, which may lead to postoperative lung injury. The objective of this paper is to systematically evaluate whether ventilation during CPB would benefit patients undergoing cardiac surgery. METHODS: We searched randomized controlled trials (RCTs) through PubMed, Embase, and Cochrane Library from inception to October 2016. Eligible studies compared clinical outcomes of ventilation versus nonventilation during CPB in patients undergoing cardiac surgery. The primary outcome includes oxygenation index (PaO2/FiO2 ratio) or alveolar to arterial oxygen tension difference (AaDO2) immediately after weaning from bypass. The secondary outcomes include postoperative pulmonary complications (PPCs), shunt fraction (Qs/Qt), hospital stay, and AaDO2 4 hours after CPB. RESULTS: Seventeen trials with 1162 patients were included in this meta-analysis. Ventilation during CPB significantly increased post-CPB PaO2/FiO2 ratio (mean difference [MD] = 21.84; 95% confidence interval [CI] = 1.30 to 42.37; P = 0.04; I = 75%) and reduced post-CPB AaDO2 (MD = -50.17; 95% CI = -71.36 to -28.99; P <0.00001; I = 74%). Qs/Qt immediately after weaning from CPB showed a significant difference between groups (MD = -3.24; 95% CI = -4.48 to -2.01; P <0.00001; I = 0%). Incidence of PPCs (odds ratio [OR] = 0.79; 95% CI = 0.42 to 1.48; P = 0.46; I = 37%) and hospital stay (MD = 0.09; 95% CI = -23 to 0.41; P = 0.58; I = 37%) did not differ significantly between groups. CONCLUSION: Ventilation during CPB might improve post-CPB oxygenation and gas exchange in patients who underwent cardiac surgery. However, there is no sufficient evidence to show that ventilation during CPB could influence long-term prognosis of these patients. The beneficial effects of ventilation during CPB are requisite to be evaluated in powerful and well-designed RCTs.

Preoperative platelet to lymphocyte and neutrophil to lymphocyte ratios are independent prognostic factors for patients undergoing lung cancer radical surgery: A single institutional cohort study.

BACKGROUND: The aim of this study was to assess the prognostic value for NSCLC patients who were scheduled to receive lung cancer radical resection. METHODS: In this cohort study (Dec.2014-Feb.2016), patients with non-small cell lung cancer (NSCLC) who underwent radical lung cancer thoracotomy were enrolled and accessed at postoperative complications, one-year overall survival (OS) and relapse-free survival (RFS). The preoperative PLR and NLR of all patients were calculated based on preoperative complete blood counts. Univariate and multivariate Cox regression analyses were performed to determine the associations of PLR and NLR with OS and RFS. RESULTS: A total of 174 NSCLC patients were studied. The results indicated that both high PLR (>148.6) and NLR (>2.9) were related to a high rate of postoperative pulmonary complications significantly (49.3%vs.29.1%, P = 0.007; 50.7% vs. 28.6%, P = 0.003). Moreover, NSCLC patients with a high PLR level (> 148.6) was significantly associated with a lower one-year OS (90.3% vs. 77.5%, P = 0.034). CONCLUSIONS: Preoperative PLR and NLR were good prognostic factors for postoperative pulmonary complications and OS in NSCLC patients undergoing radical lung cancer surgery. Thus, blood PLR and NLR would be helpful as a prognostic tool before radical lung cancer surgery.

Remote Ischemic Preconditioning for Prevention of Acute Kidney Injury in Patients Undergoing On-Pump Cardiac Surgery: A Systematic Review and Meta-Analysis.

Remote ischemic preconditioning (RIPC) may attenuate acute kidney injury (AKI). However, results of studies evaluating the effect of RIPC on AKI after cardiac surgery have been controversial and contradictory.The aim of this meta-analysis is to examine the association between RIPC and AKI after on-pump cardiac surgery.The authors searched relevant studies in PubMed, EMBASE, and the Cochrane Library through December 2015.We considered for inclusion all randomized controlled trials that the role of RIPC in reducing AKI and renal replacement therapy (RRT) among patients underwent on-pump cardiac surgical procedures.We collected the data on AKI, initiation of RRT, serum creatinine (sCr) levels, and in-hospital mortality. Random- and fixed-effect models were used for pooling data.Nineteen trials including 5100 patients were included. The results of this meta-analysis showed a significant benefit of RIPC for reducing the incidence of AKI after cardiac interventions (odds ratio [OR] = 0.84; 95% confidence interval [CI], 0.73-0.98; P = 0.02). No significant difference was found in the incidence of RRT between RIPC and control (OR, 0.76, 95% CI, 0.46-1.24; P = 0.36). In addition, compared with standard medical care, RIPC showed no significant difference in postoperative sCr (IV 0.07; 95% CI, -0.03 to 0.16; P = 0.20; postoperative day 1; IV 0.00; 95% CI, -0.08 to 0.09; P = 0.92; postoperative day 2; IV 0.04; 95% CI, -0.05 to 0.12; P = 0.39; postoperative day 3), and in-hospital mortality (OR, 1.21, 95% CI, 0.64-2.30; P = 0.56).According to the results from present meta-analysis, RIPC was associated with a significant reduction AKI after on-pump cardiac surgery but incidence of RRT, postoperative sCr, and in-hospital mortality. Further high-quality randomized controlled trials and experimental researches comparing RIPC are desirable.