Mortality and cardiac arrest rates of emergency surgery in developed and developing countries: a systematic review and meta-analysis.

BACKGROUND: The magnitude of the risk of death and cardiac arrest associated with emergency surgery and anesthesia is not well understood. Our aim was to assess whether the risk of perioperative and anesthesia-related death and cardiac arrest has decreased over the years, and whether the rates of decrease are consistent between developed and developing countries. METHODS: A systematic review was performed using electronic databases to identify studies in which patients underwent emergency surgery with rates of perioperative mortality, 30-day postoperative mortality, or perioperative cardiac arrest. Meta-regression and proportional meta-analysis with 95% confidence intervals (CIs) were performed to evaluate global data on the above three indicators over time and according to country Human Development Index (HDI), and to compare these results according to country HDI status (low vs. high HDI) and time period (pre-2000s vs. post-2000s). RESULTS: 35 studies met the inclusion criteria, representing more than 3.09 million anesthetic administrations to patients undergoing anesthesia for emergency surgery. Meta-regression showed a significant association between the risk of perioperative mortality and time (slope: -0.0421, 95%CI: from - 0.0685 to -0.0157; P = 0.0018). Perioperative mortality decreased over time from 227 per 10,000 (95% CI 134-380) before the 2000s to 46 (16-132) in the 2000-2020 s (p < 0-0001), but not with increasing HDI. 30-day postoperative mortality did not change significantly (346 [95% CI: 303-395] before the 2000s to 292 [95% CI: 201-423] in the 2000s-2020 period, P = 0.36) and did not decrease with increasing HDI status. Perioperative cardiac arrest rates decreased over time, from 113 per 10,000 (95% CI: 31-409) before the 2000s to 31 (14-70) in the 2000-2020 s, and also with increasing HDI (68 [95% CI: 29-160] in the low-HDI group to 21 [95% CI: 6-76] in the high-HDI group, P = 0.012). CONCLUSIONS: Despite increasing baseline patient risk, perioperative mortality has decreased significantly over the past decades, but 30-day postoperative mortality has not. A global priority should be to increase long-term survival in both developed and developing countries and to reduce overall perioperative cardiac arrest through evidence-based best practice in developing countries.

Long noncoding RNA SNHG25 promotes the malignancy of endometrial cancer by sponging microRNA-497-5p and increasing FASN expression.

BACKGROUND: Small nucleolar RNA host gene 25 (SNHG25), a long noncoding RNA, has been well-studied in epithelial ovarian cancer. However, the specific functions of SNHG25 in endometrial cancer (EC) have not been studied yet. In this study, we aimed to elucidate the clinical significance of SNHG25 in EC and determine the regulatory activity of SNHG25 on the tumor-associated EC phenotype. We also thoroughly explored the molecular mechanisms underlying SNHG25 function in EC. METHODS: Gene expression was measured using quantitative real-time polymerase chain reaction. The detailed functions of SNHG25 in EC were examined by performing loss-of-function experiments. Moreover, the regulatory mechanisms involving SNHG25, microRNA-497-5p, and fatty acid synthase (FASN) were unveiled using the luciferase reporter assay and RNA immunoprecipitation. RESULTS: We observed a high level of SNHG25 in EC using the TCGA dataset and our study cohort. Patients with a high SNHG25 level had shorter overall survival than those with a low SNHG25 level. SNHG25 deficiency resulted in tumor-repressing activities in EC cells by decreasing cell proliferation, migration, and invasion and promoting cell apoptosis. Furthermore, the function of SNHG25 depletion in impairing tumor growth in vivo was confirmed. SNHG25 sequestered miR-497-5p as a competing endogenous RNA in EC and consequently positively regulated FASN expression. Thus, the decrease in miR-497-5p or increase in FASN could neutralize the modulatory actions of SNHG25 knockdown in EC cells. CONCLUSIONS: The depletion of SNHG25 impedes the oncogenicity of EC by targeting the miR-497-5p/FASN axis. The newly elucidated SNHG25/miR-497-5p/FASN pathway may be a promising target for the molecular-targeted management of EC.

The augment of regulatory T cells undermines the efficacy of anti-PD-L1 treatment in cervical cancer.

BACKGROUND: Immune checkpoint inhibitors have aroused great expectation of tumor eradication. However, the effect of anti-PD-L1 treatment for cervical cancer is unsatisfactory and the underlying antagonist to anti-PD-L1 efficacy is remained to be studied. Here, we investigated the anti-tumor effect of anti-PD-L1 treatment in cervical tumor model and identified the antagonist to the therapeutic efficacy of anti-PD-L1 treatment. RESULTS: We found that PD-L1 exhibited a moderate expression in both cervical tumor cell lines and clinical samples compared to other tumor types and the para-tumor tissue respectively. Interestingly, our results showed that the anti-PD-L1 treated mice were dichotomously divided into responsive and unresponsive group after five cycles of anti-PD-L1 treatment although all the mice had the same genome background. In addition, the unresponsive tumors showed less tumor necrosis area and higher immunosuppression activity induced by regulatory T cells (Tregs) population than the responsive ones. Furthermore, we found that anti-PD-L1 treatment autonomously upregulated Tregs proliferation and frequency in multiple immune organs, and, most importantly, Tregs depletion significantly depressed the tumor growth rate and tumor weight compared with either anti-PD-L1 or anti-CD25 treatment alone. Finally, we observed that the upregulating effector CD8+ T cell is associated with the better therapeutic effect of anti-PD-L1 therapy post Tregs depletion. CONCLUSIONS: Anti-PD-L1 treatment upregulates Tregs frequency and proliferation in tumor model, and the depletion of Tregs may be a useful adjuvant strategy for anti-PD-L1 therapy of cervical cancer.

Driving Pressure-Guided Individualized Positive End-Expiratory Pressure in Abdominal Surgery: A Randomized Controlled Trial.

BACKGROUND: The optimal positive end-expiratory pressure (PEEP) to prevent postoperative pulmonary complications (PPCs) remains unclear. Recent evidence showed that driving pressure was closely related to PPCs. In this study, we tested the hypothesis that an individualized PEEP guided by minimum driving pressure during abdominal surgery would reduce the incidence of PPCs. METHODS: This single-centered, randomized controlled trial included a total of 148 patients scheduled for open upper abdominal surgery. Patients were randomly assigned to receive an individualized PEEP guided by minimum driving pressure or an empiric fixed PEEP of 6 cm H2O. The primary outcome was the incidence of clinically significant PPCs within the first 7 days after surgery, using a χ2 test. Secondary outcomes were the severity of PPCs, the area of atelectasis, and pleural effusion. Other outcomes, such as the incidence of different types of PPCs (including hypoxemia, atelectasis, pleural effusion, dyspnea, pneumonia, pneumothorax, and acute respiratory distress syndrome), intensive care unit (ICU) admission rate, length of hospital stay, and 30-day mortality were also explored. RESULTS: The median value of PEEP in the individualized group was 10 cm H2O. The incidence of clinically significant PPCs was significantly lower in the individualized PEEP group compared with that in the fixed PEEP group (26 of 67 [38.8%] vs 42 of 67 [62.7%], relative risk = 0.619, 95% confidence intervals, 0.435-0.881; P = .006). The overall severity of PPCs and the area of atelectasis were also significantly diminished in the individualized PEEP group. Higher respiratory compliance during surgery and improved intra- and postoperative oxygenation was observed in the individualized group. No significant differences were found in other outcomes between the 2 groups, such as ICU admission rate or 30-day mortality. CONCLUSIONS: The application of individualized PEEP based on minimum driving pressure may effectively decrease the severity of atelectasis, improve oxygenation, and reduce the incidence of clinically significant PPCs after open upper abdominal surgery.

Ebosin Ameliorates Psoriasis-Like Inflammation of Mice via miR-155 Targeting tnfaip3 on IL-17 Pathway.

Psoriasis is a recurrent autoimmune skin disease with aberrant regulation of keratinocytes and immunocytes. There is no universally accepted single treatment available for psoriasis, and the establishment of a common treatment option to control its signs and symptoms is urgently needed. Here, we found Ebosin, a novel exopolysaccharide isolated from Streptomyces sp. 139 by our lab, not only could ameliorate inflammation in LPS-induced keratinocytes through IKK/NF-kapaB pathway, but also attenuate psoriatic skin lesions and reduce inflammatory factors expression in imiquimod (IMQ)-mediated psoriatic mice. Except for inhibiting the expression of epidermal differentiation related proteins, Ebosin significantly increased the percentage of CD4+Foxp3+CD25+ Tregs and decreased CD4+IL17A+ Th17 cells in psoriatic mice. Furthermore, we demonstrate that Ebosin significantly suppressed the IL-17 signaling pathway via A20 (encoded by tnfaip3) in vivo. As the direct binding of tnfaip3 to miR-155 has been demonstrated by luciferase reporter assay, and Ebosin has been demonstrated to inhibit miR-155 level in vitro and in vivo, our study first indicates that Ebosin reduces inflammation through the miR-155-tnfaip3-IL-17 axis and T cell differentiation in a psoriasis-like model. Thus, we conclude that Ebosin can act as a promising therapeutic candidate for the treatment of psoriasis.

Siomycin A induces reactive oxygen species-mediated cytotoxicity in ovarian cancer cells.

Ovarian cancer is one of the leading causes of cancer-related death among women worldwide and accounts for 4% of all cancer cases in female patients. To date, ovarian cancer has the poorest prognosis among all types of gynecological cancer; thus, it is necessary to identify prospective therapeutic options. Previous studies have demonstrated the involvement of reactive oxygen species (ROS) in the cytotoxicity of various anticancer drugs against several types of carcinoma, including ovarian cancer. The present study aimed to investigate the anticancer effects of Siomycin A, a thiopeptide antibiotic, on the ovarian cancer cell lines PA1 and OVCAR3. To determine the viability of these cells following exposure to Siomycin A, the MTT assay was used, and apoptosis was determined by ELISA. In addition, mitochondrial membrane potential was determined by JC1 staining, and cellular ROS levels were assessed by dichlorodihydrofluorescein diacetate staining in the presence and absence of antioxidant NAC. The subsequent levels of antioxidant enzymes and glutathione were also determined following Siomycin A treatment in the two cell lines. A combination study with Siomycin A and cisplatin indicated enhanced efficiency of the drugs on ovarian cancer cell viability. The results of the present study also demonstrated that Siomycin A induced ROS production, inhibited the major antioxidant enzymes, including catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase and intracellular GSH in PA1 and OVCAR3 cells, and inhibited the cell viability with an IC50 of ~5.0 and 2.5 µM after 72 h respectively compared with the untreated controls. Additionally, the Siomycin A-induced ROS production further targeted apoptotic cell death by impairing the mitochondrial membrane potential and modulating the levels of pro- and antiapoptotic proteins compared with those in the corresponding control groups. The administration of the antioxidant N-acetylcysteine significantly abrogated the cytotoxic effects of Siomycin A. In conclusion, the results of the present study demonstrated the role of ROS in Siomycin A-mediated cytotoxicity in ovarian cancer cells.

Knockdown of Rab7a suppresses the proliferation, migration, and xenograft tumor growth of breast cancer cells.

Breast cancer is a common invasive cancer in women. Ras-related protein Rab-7a (Rab7a) is involved in late endocytic trafficking, while its role in breast cancer is largely unclear. In the present study, we investigated the role of Rab7a in breast cancer. Comparing with adjacent breast tissues, Rab7a expression was increased in breast cancer tissues. Using lentivirus-mediated knockdown strategy, we found that Rab7a silencing inhibited the proliferation and colony formation of MDA-MB-231 cells. Apoptosis and G2 cell cycle arrest were induced in Rab7a knockdown. By contrast, Rab7a suppressed the apoptosis and promoted proliferation and colony formation of MCF-7 cells. The migration of MDA-MB-231 cells was suppressed by Rab7a knockdown. In vivo, depletion of Rab7a inhibited the xenograft tumor development of MDA-MB-231 cells. Altogether, our results highlight the novel function of Rab7a in the proliferation, invasion, and xenograft tumor development of breast cancer cells.

Inflammasome in the Pathogenesis of Pulmonary Diseases.

Lung diseases are common and significant causes of illness and death around the world. Inflammasomes have emerged as an important regulator of lung diseases. The important role of IL-1 beta and IL-18 in the inflammatory response of many lung diseases has been elucidated. The cleavage to turn IL-1 beta and IL-18 from their precursors into the active forms is tightly regulated by inflammasomes. In this chapter, we structurally review current evidence of inflammasome-related components in the pathogenesis of acute and chronic lung diseases, focusing on the "inflammasome-caspase-1-IL-1 beta/IL-18" axis.

Closer to a Uniform Language in Colposcopy: Study on the Potential Application of 2011 International Federation for Cervical Pathology and Colposcopy Terminology in Clinical Practice.

As the newest colposcopic terminology, the 2011 International Federation for Cervical Pathology and Colposcopy (IFCPC) classification provides standardized interpretation of colposcopic findings. In this study, we analyzed the colposcopic accuracy and the significance of individual findings according to the 2011 IFCPC classification in 525 patients, reviewed by 13 trained colposcopists. Results show that colposcopic diagnoses are in 64.95% perfect agreement with cervical pathology, with 63.64% sensitivity and 96.01% specificity for high-grade squamous intraepithelial lesion (HSIL+). And the accuracy is reproducible across different experienced examiners. Many individual findings, especially the two new signs, inner border sign and ridge sign, are proved to have good predictive accuracy, while iodine negativity demonstrates an inferior performance. However, the distribution of three cervical transformation zone (TZ) types is heterogeneous in examiners. A comparison was also made of the findings of another two colposcopists without nomenclature training according to the Reid Colposcopic Index (RCI), modified RCI, and Swede Score. Results show that colposcopic accuracies in them are lower than in those nomenclature trained colposcopists. The 2011 IFCPC nomenclature improves colposcopic accuracy in trained colposcopists, like speaking the same language. However, the reproducibility of TZ and the predictive value of a few signs remain to be discussed.

MicroRNA-873 is a Potential Serum Biomarker for the Detection of Ectopic Pregnancy.

BACKGROUND: Ectopic pregnancy (EP) refers to the implantation of the zygote outside the uterine cavity. In clinical practice, the diagnosis of EP relies on a combination of ultrasound findings and serum human chorionic gonadotrophin (hCG) measurements. However, the need for serial hCG measurements increases the risk of tubal rupture and death, underscoring the need to identify biomarkers for the early detection of EP. METHODS: The serum concentrations of 21 microRNAs (miRNAs) associated with pregnancy or with known placental expression, as well as serum hCG and progesterone levels were analyzed 36 patients with viable intrauterine pregnancy (VIP), 30 patients with spontaneous abortion (SA), and 34 patients with EP using specific assay kits and reverse transcription PCR. The diagnostic performance of the different serum markers for detecting EP was analyzed by ROC curve analysis. RESULTS: Five miRNAs were differentially expressed between the three groups, of which miR-873 and miR-223 were significantly lower in EP than in VIP and SA patients and did not change significantly according to gestational age, and miR-323 was significantly higher in EP than in VIP and SA. As a single marker, miR-873 had the highest sensitivity for detecting EP at 61.76% (at a fixed specificity of 90%). In comparison, the combination of hCG, progesterone and miR-873 had the highest sensitivity for detecting EP at 79.41% (at a fixed specificity of 90%). CONCLUSION: Although further validation in large-scale prospective studies is necessary, our results suggest that miR-873 could be a valuable noninvasive and stable biomarker for the early detection of EP.

Perioperative angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers for preventing mortality and morbidity in adults.

BACKGROUND: Perioperative hypertension requires careful management. Angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II type 1 receptor blockers (ARBs) have shown efficacy in treating hypertension associated with surgery. However, there is lack of consensus about whether they can prevent mortality and morbidity. OBJECTIVES: To systematically assess the benefits and harms of administration of ACEIs or ARBs perioperatively for the prevention of mortality and morbidity in adults (aged 18 years and above) undergoing any type of surgery under general anaesthesia. SEARCH METHODS: We searched the current issue of the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 12), Ovid MEDLINE (1966 to 8 December 2014), EMBASE (1980 to 8 December 2014), and references of the retrieved randomized trials, meta-analyses, and systematic reviews. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing perioperative administration of ACEIs or ARBs with placebo in adults (aged 18 years and above) undergoing any type of surgery under general anaesthesia. We excluded studies in which participants underwent procedures that required local anaesthesia only, or participants who had already been on ACEIs or ARBs. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, assessed the risk of bias, and extracted data. We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included seven RCTs with a total of 571 participants in the review. Two of the seven trials involved 36 participants undergoing non-cardiac vascular surgery (infrarenal aortic surgery), and five involved 535 participants undergoing cardiac surgery, including valvular surgery, coronary artery bypass surgery, and cardiopulmonary bypass surgery. The intervention was started from 11 days to 25 minutes before surgery in six trials and during surgery in one trial. We considered all seven RCTs to carry a high risk of bias. The effects of ACEIs or ARBs on perioperative mortality and acute myocardial infarction were uncertain because the quality of the evidence was very low. The risk of death was 2.7% in the ACEIs or ARBs group and 1.6% in the placebo group (risk ratio (RR) 1.61; 95% confidence interval (CI) 0.44 to 5.85). The risk of acute myocardial infarction was 1.7% in the ACEIs or ARBs group and 3.0% in the placebo group (RR 0.55; 95% CI 0.14 to 2.26). ACEIs or ARBs may improve congestive heart failure (cardiac index) perioperatively (mean difference (MD) -0.60; 95% CI -0.70 to -0.50, very low-quality evidence). In terms of rate of complications, there was no difference in perioperative cerebrovascular complications (RR 0.48; 95% CI 0.18 to 1.28, very low-quality evidence) and hypotension (RR 1.95; 95% CI 0.86 to 4.41, very low-quality evidence). Cardiac surgery-related renal failure was not reported. ACEIs or ARBs were associated with shortened length of hospital stay (MD -0.54; 95% CI -0.93 to -0.16, P value = 0.005, very low-quality evidence). These findings should be interpreted cautiously due to likely confounding by the clinical backgrounds of the participants. ACEIs or ARBs may shorten the length of hospital stay, (MD -0.54; 95% CI -0.93 to -0.16, very low-quality evidence) Two studies reported adverse events, and there was no evidence of a difference between the ACEIs or ARBs and control groups. AUTHORS' CONCLUSIONS: Overall, this review did not find evidence to support that perioperative ACEIs or ARBs can prevent mortality, morbidity, and complications (hypotension, perioperative cerebrovascular complications, and cardiac surgery-related renal failure). We found no evidence showing that the use of these drugs may reduce the rate of acute myocardial infarction. However, ACEIs or ARBs may increase cardiac output perioperatively. Due to the low and very low methodology quality, high risk of bias, and lack of power of the included studies, the true effect may be substantially different from the observed estimates. Perioperative (mainly elective cardiac surgery, according to included studies) initiation of ACEIs or ARBs therapy should be individualized.

Efficacy of dexmedetomidine on postoperative shivering: a meta-analysis of clinical trials.

PURPOSE: Shivering is a frequent complication in the postoperative period. The aim of the current meta-analysis was to assess the efficacy of dexmedetomidine on postoperative shivering. METHODS: Two researchers independently searched PubMed, EMBASE and the Cochrane Central Register of Controlled Trials for controlled clinical trials. The meta-analysis was performed by Review Manager. RESULTS: Thirty-nine trials with 2,478 patients were included in this meta-analysis. Dexmedetomidine reduced postoperative shivering compared with placebo (risk ratio [RR] = 0.26; 95% confidence interval [CI]: 0.20 to 0.34), with a minimum effective dose of 0.5 µg·kg(-1) (RR = 0.36; 95% CI: 0.21 to 0.60). The anti-shivering effect can be achieved both intravenously and epidurally when administered within two hours prior to the end of surgery. The efficacy of dexmedetomidine was similar to widely used anti-shivering agents, such as fentanyl, meperidine, tramadol, clonidine and so on; however, dexmedetomidine may increase the incidence of sedation, hypotension, bradycardia and dry mouth. CONCLUSIONS: The present meta-analysis indicates that dexmedetomidine shows superiority over placebo, but not over other anti-shivering agents. Therefore, considering its high price and potential adverse events, dexmedetomidine may not be appropriate solely for the purpose of the prevention of postoperative shivering.

Da-cheng-qi decoction, a traditional Chinese herbal formula, for intestinal obstruction: systematic review and meta-analysis.

BACKGROUND: This study was aimed at determining the effects and safety of Da-Cheng-Qi decoction (DCQD) or DCQD combined with conservative therapy in patients with intestinal obstruction. MATERIALS AND METHODS: PubMed, EMBASE, Cochrane Controlled Trials Register, and several other databases were searched. Randomised controlled trials (RCTs) of DCQD or DCQD plus conservative therapy in patients with intestinal obstruction were eligible. Therapeutic effect was estimated by the improvement of clinical manifestations and diagnostic imaging; dichotomous/ordinal data assessment of overall response to therapy, adverse effects; or continuous variable were identified, including time to first bowel movement, time to first flatus, length of hospital stay. RESULTS: Sixty eligible RCTs including 6,095 patients were identified. Response rate: (1) DCQD versus conservative therapy (6 RCTs, 361 patients, RR of respond =1.13; 95% CI 0.97 to 1.31). (2) DCQD plus conservative therapy versus conservative therapy (48 RCTs, 4,916 patients, RR of respond =1.25 which favoured DCQD plus conservative therapy; 95% CI 1.20 to 1.30). Treatment effect remained similar when RCTs at high risk of bias were excluded. Time to first flatus postoperatively: (1) DCQD versus conservative therapy (2 RCTs, 240 patients, SMD=-3.65; 95% CI -8.17 to 0.87). (2) DCQD plus conservative therapy versus conservative therapy (11 RCTs, 1,040 patients, SMD=-2.09 which favoured DCQD plus conservative therapy; 95% CI -3.04 to -1.15). CONCLUSION: DCQD combined with conservative therapy may increase the success rate of conservative therapy for intestinal obstruction significantly and can shorten the duration of postoperative ileus in patients undergoing abdominal surgery compared with conservative therapy alone.

Hydrogen sulfide preconditioning protects rat liver against ischemia/reperfusion injury by activating Akt-GSK-3ß signaling and inhibiting mitochondrial permeability transition.

Hydrogen sulfide (H2S) is the third most common endogenously produced gaseous signaling molecule, but its impact on hepatic ischemia/reperfusion (I/R) injury, especially on mitochondrial function, remains unclear. In this study, rats were randomized into Sham, I/R, ischemia preconditioning (IPC) or sodium hydrosulfide (NaHS, an H2S donor) preconditioning groups. To establish a model of segmental (70%) warm hepatic ischemia, the hepatic artery, left portal vein and median liver lobes were occluded for 60 min and then unclamped to allow reperfusion. Preconditioning with 12.5, 25 or 50 µmol/kg NaHS prior to the I/R insult significantly increased serum H2S levels, and, similar to IPC, NaHS preconditioning decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the plasma and prevented hepatocytes from undergoing I/R-induced necrosis. Moreover, a sub-toxic dose of NaHS (25 µmol/kg) did not disrupt the systemic hemodynamics but dramatically inhibited mitochondrial permeability transition pore (MPTP) opening and thus prevented mitochondrial-related cell death and apoptosis. Mechanistic studies revealed that NaHS preconditioning markedly increased the expression of phosphorylated protein kinase B (p-Akt), phosphorylated glycogen synthase kinase-3 beta (p-GSK-3ß) and B-cell lymphoma-2 (Bcl-2) and decreased the release of mitochondrial cytochrome c and cleaved caspase-3/9 levels. Therefore, NaHS administration prior to hepatic I/R ameliorates mitochondrial and hepatocellular damage through the inhibition of MPTP opening and the activation of Akt-GSK-3ß signaling. Furthermore, this study provides experimental evidence for the clinical use of H2S to reduce liver damage after perioperative I/R injury.