High Respiratory and Cardiac Drive Exacerbate Secondary Lung Injury in Patients With Critical Illness.

The high respiratory and cardiac drive is essential to the host-organ unregulated response. When a primary disease and an unregulated secondary response are uncontrolled, the patient may present in a high respiratory and cardiac drive state. High respiratory drive can cause damage to the lungs, pulmonary circulation, and diaphragm, while high cardiac drive can lead to fluid leakage and infiltration as well as pulmonary interstitial edema. A "respiratory and cardiac dual high drive" state may be a sign of an unregulated response and can lead to secondary lung injury through the increase of transvascular pressure and pulmonary microcirculation injury. Ultrasound examination of the lung, heart, and diaphragm is important when evaluating the phenotype of high respiratory drive in critically ill patients. Ultrasound assessment can guide sedation, analgesia, and antistress treatment and reduce the risk of high respiratory and cardiac drive-induced lung injury in these patients.

Local palliative therapies for unresectable malignant biliary obstruction: radiofrequency ablation combined with stent or biliary stent alone? An updated meta-analysis of nineteen trials.

BACKGROUND: Recently, there has been a burgeoning interest in radiofrequency ablation combined with stent (RFA + Stent) for unresectable malignant biliary obstruction (MBO). This study aimed to perform a meta-analysis to evaluate the efficacy and safety of RFA + Stent compared with biliary stent alone. METHODS: We searched PubMed, Cochrane Library, Embase, and Web of Science databases from their inception dates to June 20, 2021, for studies that compared RFA + Stent and stent alone for unresectable MBO. The main outcomes were survival, patency, and adverse effects. All meta-analyses were calculated using the random-effects model. RESULTS: A total of 19 studies involving 1946 patients were included in this study. Compared with stent alone, RFA + Stent was significantly associated with better overall survival (HR 0.55; 95% CI 0.48, 0.63; P < 0.00001), longer mean survival time (SMD 2.20; 95% CI 1.17, 3.22; P < 0.0001), longer mean stent patency time (SMD 1.37; 95% CI 0.47, 2.26; P = 0.003), higher stent patency at 6 months (OR 2.82; 95% CI 1.54, 5.18; P = 0.0008). The two interventions had similar incidence of postoperative abdominal pain (OR 1.29; 95% CI 0.94, 1.78; P = 0.11), mild bleeding (OR 1.28; 95% CI 0.65, 2.54; P = 0.48), cholangitis (OR 1.09; 95% CI 0.76, 1.55; P = 0.65), pancreatitis (OR 1.39; 95% CI 0.82, 2.38; P = 0.22). Furthermore, the serum bilirubin levels and stricture diameter after operations were significantly alleviated than before operations, but the degree of alleviation between the two groups were not significantly different (all P > 0.05). CONCLUSION: Although the alleviation of serum bilirubin and stricture diameter did not differ between the two interventions, RFA + Stent can significantly improve the survival and stent patency with comparable procedure-related adverse events than stent alone. Thus, RFA + Stent should be recommended as an attractive alternative to biliary stent alone for patients with unresectable MBO.

Clinical efficacy and safety of robotic distal gastrectomy for gastric cancer: a systematic review and meta-analysis.

BACKGROUND: Robotic distal gastrectomy (RDG) is a new technique that is rapidly gaining popularity and may help overcome the limitations of laparoscopic distal gastrectomy (LDG); however, its safety and therapeutic efficacy remain controversial. Therefore, this meta-analysis was performed to evaluate the safety and efficacy of RDG. METHODS: We searched PubMed, EMBASE, the Cochrane Library, and Web of Science for studies that compared RDG and LDG and were published between the time of database inception and May 2021. We assessed the bias risk of the observational studies using ROBIN-I, and a random effect model was always applied. RESULTS: The meta-analysis included 22 studies involving 5386 patients. Compared with LDG, RDG was associated with longer operating time (Mean Difference [MD] = 43.88, 95% CI = 35.17-52.60), less intraoperative blood loss (MD = - 24.84, 95% CI = - 41.26 to - 8.43), a higher number of retrieved lymph nodes (MD = 2.41, 95% CI = 0.77-4.05), shorter time to first flatus (MD = - 0.09, 95% CI = - 0.15 to - 0.03), shorter postoperative hospital stay (MD = - 0.68, 95% CI = - 1.27 to - 0.08), and lower incidence of pancreatic fistula (OR = 0.23, 95% CI = 0.07-0.79). Mean proximal and distal resection margin distances, time to start liquid and soft diets, and other complications were not significantly different between RDG and LDG groups. However, in the propensity-score-matched meta-analysis, the differences in time to first flatus and postoperative hospital stay between the two groups lost significance. CONCLUSIONS: Based on the available evidence, RDG appears feasible and safe, shows better surgical and oncological outcomes than LDG and, comparable postoperative recovery and postoperative complication outcomes.

Immune checkpoint blockade in the treatment of malignant tumor: current statue and future strategies.

After being stagnant for decades, there has finally been a paradigm shift in the treatment of cancer with the emergence and application of immune checkpoint inhibitors (ICIs). The most extensively utilized ICIs are targeting the pathways involving programmed death-1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4). PD-1, as an crucial immune inhibitory molecule, by and large reasons the immune checkpoint response of T cells, making tumor cells get away from immune surveillance. Programmed cell death ligand-1 (PD-L1) is exceptionally expressed in most cancers cells and approves non-stop activation of the PD-1 pathway in the tumor microenvironment. PD-1/PD-L1 inhibitors can block the combination of PD-1 and PD-L1, inhibit hostile to regulatory signals, and restore the activity of T cells, thereby bettering immune response. The current researchers assume that the efficacy of these drugs is related to PD-L1 expression in tumor tissue, tumor mutation burden (TMB), and other emerging biomarkers. Although malignant tumors can benefit from the immunotherapy of PD-1/PD-L1 inhibitors, formulating a customized medication model and discovering biomarkers that can predict efficacy are the new trend in the new era of malignant tumor immunotherapy. This review summarizes the mechanism of action of PD-1/PD-L1 inhibitors, their clinical outcomes on various malignant tumors, their efficacy biomarkers, as well as predictive markers of irAEs.

PCAT6 may be a new prognostic biomarker in various cancers: a meta-analysis and bioinformatics analysis.

BACKGROUND: LncRNA prostate cancer-associated transcript 6 (PCAT6) has been reported to be dysregulated in several cancers and is associated with tumor progression. Here, we have performed a meta-analysis to assess the general prognostic role of PCAT6 in malignancies. METHODS: Four public databases (Embase, Pubmed, Web of Science, Cochrane Library) were used to identify eligible studies, then data was extracted and associations between prognostic indicators and clinical characteristics were combined to estimate hazard ratio (HR) or odds ratio (OR) with a 95% confidence interval (CI). Publication bias was measured using the Begg's test, and the stability of the combined results was measured using sensitivity analysis. Subsequently, results were validated using Gene Expression Profiling Interactive Analysis (GEPIA) and the National Genomics Data Center (NGDC). RESULTS: Ten studies were considered eligible for inclusion. In total, 937 patients and eight types of cancer were included. Our results revealed that overexpression of PCAT6 was significantly associated with a shorter OS (HR = 1.82; 95% CI, [1.40, 2.38]; P < 0.0001) and progression-free survival (PFS) (HR = 1.66; 95% CI, [1.22, 2.25]; P < 0.0001) in cancer patients, and that PCAT6 overexpression was significantly associated with individual tumor clinicopathological parameters, including TNM stage (OR = 0.29; 95% CI, [0.09, 0.94]; P = 0.04), gender (OR = 1.84; 95% CI, [1.31, 2.59]; P = 0.0005), and whether the tumor was metastatic (OR = 5.02; 95% CI, [1.36, 18.57]; P = 0.02). However, PCAT6 overexpression was not correlated with patient age and tumor differentiation. PCAT6 expression was significantly up-regulated in four types of cancer, which was validated using the GEPIA cohort. Combining OS and disease-free survival (DFS) of these four types of cancer revealed a shorter OS and DFS in patients with PCAT6 overexpression. PCAT6 expression in various types of cancer was also validated in NGDC. A total of eight cancers were analyzed and PCAT6 was highly expressed in all eight cancers. Further functional predictions suggest that PCAT6 is correlated with tumor prognosis, and that PCAT6 may be useful as a new tumor-specific marker. CONCLUSIONS: LncRNA PCAT6 is highly expressed in multiple cancer types and its upregulation was significantly associated with patient prognosis and poorer clinical features, thereby suggesting that PCAT6 may be a novel prognostic factor in multiple cancer types.

Comparison of intraoperative endoscopic retrograde cholangiopancreatography and laparoscopic common bile duct exploration combined with laparoscopic cholecystectomy for treating gallstones and common bile duct stones: a systematic review and meta-analysis.

BACKGROUND: This study aimed to compare the efficacy and safety of laparoscopic cholecystectomy combined with intraoperative endoscopic retrograde cholangiopancreatography (LC-IntraERCP) and laparoscopic cholecystectomy combined with laparoscopic common bile duct exploration (LC-LCBDE) to determine which one-stage therapeutic strategy provides better outcomes for patients with gallstones and common bile duct stones. METHODS: Cochrane Library, EMBASE, PubMed, and Web of Science databases were searched to identify eligible articles from the database inception to September 2020. The revised Cochrane risk of bias tools for randomized trials (RoB-2) and non-randomized interventions (ROBINS-I) was used to assess the quality of the included studies. The overall quality of evidence was assessed through the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool. The primary outcomes consisted of surgical success, retained stones, and overall postoperative complications, while secondary outcomes included postoperative bleeding, postoperative pancreatitis, postoperative bile leakage, conversion to laparotomy, and operative time. RESULTS: Eight studies (four RCTs and four Non-RCTs with high quality) with 2948 patients were included. No significant difference was seen between the two groups regarding surgical success, overall postoperative complications, conversion to laparotomy, and operative time. The meta-analysis demonstrated that in the LC-IntraERCP group, the rate of retained stones (OR 0.51, 95% CI 0.28-0.91) and postoperative bile leakage were lower (OR 0.25, 95% CI 0.09-0.69), while in the LC-LCBDE group, postoperative bleeding (OR 5.24, 95% CI 1.65-16.65) and postoperative pancreatitis (OR 4.80, 95% CI 2.35-9.78) decreased. CONCLUSIONS: LC-IntraERCP and LC-LCBDE exhibited similar efficacies when surgical success rate, overall postoperative complications, conversion to laparotomy, and operative time were compared. However, LC-IntraERCP is probably to be more effective in terms of lowering the rate of retained stones.

Reduction of risk of infection during elective laparoscopic cholecystectomy using prophylactic antibiotics: a systematic review and meta-analysis.

BACKGROUND: Whether perioperative administration is required in elective laparoscopic cholecystectomy (LC) in patients with low risk of infection remains controversial. OBJECTIVE: To investigate whether perioperative use of prophylactic antibiotics during elective LC can reduce the incidence of postoperative infection using a meta-analysis. METHODS: Pubmed, Cochrane Library, Embase, and reference lists were searched up to October 26, 2020, for randomized controlled trials (RCTs) of the perioperative use of antibiotics during LC. A systematic review with meta-analysis, meta-regression, and GRADE (Grading of Recommendations Assessment, Development and Evaluation) of the evidence was conducted. The Cochrane (RoB 2.0) tool was used to assess the risk of bias. RESULT: A total of 14 RCTs were ultimately included in the meta-analysis, involving a total of 4360 patients. The incidence of surgical site infections, distant infections, and overall infections was investigated and the relationship with the perioperative use of prophylactic antibiotics during LC analyzed. The results indicated that in low-risk patients undergoing elective LC, prophylactic antibiotics reduce the incidence of surgical site infections (RR 0.66; 95% CI 0.45-0.98), with a moderate GRADE of evidence, distant infections (RR 0.34; 95% CI 0.16-0.73), with a low GRADE of evidence and overall infections (RR 0.57; 95% CI 0.40-0.80), with a moderate GRADE of evidence. CONCLUSIONS: The present meta-analysis demonstrates that the perioperative use of antibiotics in LC is effective in low-risk patients, possibly reducing the incidence of surgical site infections, distant infections, and overall infections. However, in view of the limitations of the study, it is recommended that studies with a more rigorous design (for downgraded factors) and larger sample size should be conducted in the future so that the conclusions above can be further verified through key result indicators.

Assessment of Pulmonary Circulation of Critically Ill Patients Based on Critical Care Ultrasound.

Pulmonary circulation is crucial in the human circulatory system, facilitating the oxygenation of blood as it moves from the right heart to the lungs and then to the left heart. However, during critical illness, pulmonary microcirculation can be vulnerable to both intrapulmonary and extrapulmonary injuries. To assess these potential injuries in critically ill patients, critical point-of-care ultrasound can be used to quantitatively and qualitatively evaluate the right atrium, right ventricle, pulmonary artery, lung, pulmonary vein, and left atrium along the direction of blood flow. This assessment is particularly valuable for common ICU diseases such as acute respiratory distress syndrome (ARDS), sepsis, pulmonary hypertension, and cardiogenic pulmonary edema. It has significant potential for diagnosing and treating these conditions in critical care medicine.

Yes-associated protein inhibition ameliorates carbon tetrachloride-induced acute liver injury in mice by reducing VDR.

Carbon tetrachloride (CCl4) has a wide range of toxic effects, especially causing acute liver injury (ALI), in which rapid compensation for hepatocyte loss ensures liver survival, but proliferation of surviving hepatocytes (known as endoreplication) may imply impaired residual function. Yes-associated protein (YAP) drives hepatocytes to undergo endoreplication and ploidy, the underlying mechanisms of which remain a mystery. In the present study, we uncover during CCl4-mediated ALI accompanied by increased hepatocytes proliferation and YAP activation. Notably, bioinformatics analyses elucidate that hepatic-specific deletion of YAP substantially ameliorated CCl4-induced hepatic proliferation, effectively decreased the vitamin D receptor (VDR) expression. Additionally, a mouse model of acute liver injury substantiated that inhibition of YAP could suppress hepatocytes proliferation via VDR. Furthermore, we also disclosed that the VDR agonist nullifies CCl4-induced ALI alleviated by the YAP inhibitor in vivo. Importantly, hepatocytes were isolated from mice, and it was spotlighted that the anti-proliferative impact of the YAP inhibitor was abolished by the activation of VDR within these hepatocytes. Similarly, primary hepatic stellate cells (HSCs) were isolated and it was manifested that YAP inhibitor suppressed HSC activation via VDR during acute liver injury. Our findings further elucidate the YAP's role in ALI and may provide new avenues for protection against CCl4-drived acute liver injury.

Activated PARP1/FAK/COL5A1 signaling facilitates the tumorigenesis of cholesterol-resistant ovarian cancer cells through promoting EMT.

Cancer cells require plentiful cholesterol for membrane biogenesis and other functional needs due to fast proliferating, leading to the interaction of cholesterol or its metabolites with cancer-related pathways. However, the impact of long-lasting high cholesterol concentrations on tumorigenesis and its underlying mechanisms remains largely unexplored. To the best of our knowledge, this study is the first to establish a cholesterol-resistant ovarian cancer cells, whose intracellular total cholesterol level up to 6-8 mmol/L. We confirmed that high cholesterol facilitated the progression of ovarian cancer in vitro and in vivo. Notably, our findings revealed significant upregulation of collagen type V alpha 1 chain (COL5A1) expression in cholesterol-resistant ovarian cancer cells and human ovarian cancer tissue, which was depended on FAK/Src activation. Mechanistically, PARP1 directly bound to FAK in response to activate FAK/Src/COL5A1 signaling. Intriguingly, COL5A1 depletion significantly impeded the tumorigenesis of these cells, concomitant with a decrease in epithelial-mesenchymal transition (EMT) progression. In conclusion, PARP1/FAK/COL5A1 signaling activation facilitated progression of cholesterol-resistant ovarian cancer cells by promoting EMT, thereby broadening a new therapeutic opportunity.

Comparative efficacy and safety of local palliative therapeutics for unresectable malignant biliary obstruction: a Bayesian network meta-analysis.

BACKGROUND: Both radiofrequency ablation (RFA), photodynamic therapy (PDT), and biliary stent alone are common local palliative therapies for unresectable malignant biliary obstruction (MBO), but the best modality is uncertain. RESEARCH DESIGN AND METHODS: Embase, Cochrane Library, PubMed, and Web of Science were systematically searched up to 30 January 2022, for eligible studies that compared either two or all modalities in unresectable MBO. RESULTS: Thirty-three studies with 2974 patients were included in this study. The PDT+Stent and RFA+Stent groups had better overall survival and longer mean survival time than Stent alone (all P < 0.05). Moreover, patients with RFA+Stent demonstrated better mean duration of stent patency (MD: 2.0, 95%CI,1.1 to 2.8, P < 0.05) than Stent alone. The three modalities had similar postoperative mild bleeding, cholangitis, and pancreatitis (all P ≥ 0.05). According to network ranking, PDT+Stent was most likely to provide better survival, RFA+Stent was most likely to maintain stent patency. CONCLUSIONS: RFA or PDT plus biliary stent is effective and safe local palliative therapy for unresectable MBO, but the current studies cannot absolutely determine which modality is the best. We should offer patients the most appropriate treatment according to the advantage of each therapy and the patient's performance status.

Early predictive value of circulating biomarkers for sorafenib in advanced hepatocellular carcinoma.

INTRODUCTION: Sorafenib is currently the first-line therapeutic regimen for patients with advanced hepatocellular carcinoma (HCC). However, many patients did not experience any benefit and suffered extreme adverse events and heavy economic burden. Thus, the early identification of patients who are most likely to benefit from sorafenib is needed. AREAS COVERED: This review focused on the clinical application of circulating biomarkers (including conventional biomarkers, immune biomarkers, genetic biomarkers, and some novel biomarkers) in advanced HCC patients treated with sorafenib. An online search on PubMed, Web of Science, Embase, and Cochrane Library was conducted from the inception to 15 August 2021. Studies investigating the predictive or prognostic value of these biomarkers were included. EXPERT OPINION: The distinction of patients who may benefit from sorafenib treatment is of utmost importance. The predictive roles of circulating biomarkers could solve this problem. Many biomarkers can be obtained by liquid biopsy, which is a less or noninvasive approach. The short half-life of sorafenib could reflect the dynamic changes of tumor progression and monitor the treatment response. Circulating biomarkers obtained from liquid biopsy resulted as a promising assessment method in HCC, allowing for better treatment decisions in the near future. ABBREVIATIONS: Alpha-fetoprotein (AFP); American Association for the Study of Liver Diseases (AASLD); Angiopoietin (Ang); Barcelona Clinic Liver Cancer stage (BCLC); Circulating endothelial progenitor (CEP); Circulating free DNA (cfDNA); Complete response (CR); Des-γ-carboxy prothrombin (DCP); Endothelium-derived nitric oxide synthase (eNOS); Hepatocellular carcinoma (HCC); Hepatocyte growth factor (HGF); Hepatoma arterial-embolization prognosis score (HAP); High mobility group box 1 (HMgb1); Interferon-gamma (IFN-γ); Long non-coding RNA (lncRNAs); Micro RNAs (miRNAs); Monocyte-to-lymphocyte ratio (MLR); National Comprehensive Cancer Network (NCCN); Neutrophil-lymphocyte ratio (NLR); Newcastle-Ottawa Scale (NOS); Nitric oxide (NO); Overall survival (OS); Partial response (PR); Platelet-lymphocyte ratio (PLR); Prediction of survival in advanced sorafenib-treated HCC (PROSASH); Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA); Prognostic nutritional index (PNI); Progression-free survival (PFS); Progressive disease (PD); Randomized controlled trials (RCTs); Response Evaluation Criteria in Solid Tumors (RECIST); Single nucleotide polymorphisms (SNPs); Sorafenib advanced HCC prognosis score (SAP); Stable disease (SD); Time to progression (TTP); Transcatheter arterial chemoembolization (TACE); Vascular endothelial growth factor (VEGF).

Proximal Gastrectomy Versus Total Gastrectomy for Siewert II/III Adenocarcinoma of the Gastroesophageal Junction: a Systematic Review and Meta-analysis.

BACKGROUND: The incidence of adenocarcinoma of the esophagogastric junction (AEG) has rapidly increased in recent years. Popular surgical approaches for AEG are proximal gastrectomy (PG) and total gastrectomy (TG), but it is controversial as to which approach is superior. Therefore, we conducted a systematic review and meta-analysis to evaluate the short- and long-term clinical outcomes of PG and TG for AEG. METHODS: PubMed, Embase, Web of Science, and Cochrane Library were searched from inception to 1 June 2021. The Newcastle-Ottawa scale was used to conduct quality assessments, and RevMan (Version 5.4) was used to perform the meta-analysis. RESULTS: In all, 1,734 patients with Siewert II/III AEG in 12 studies were included in the meta-analysis. PG was associated with less number of harvested lymph nodes (WMD = - 9.00, 95% CI - 12.61 to - 5.39, P < 0.00001), smaller tumor size (WMD = - 1.02, 95% CI - 1.71 to - 0.33, P = 0.004), shorter hospital length of stay (WMD = - 3.99, 95% CI - 7.27 to - 0.71, P = 0.02), and better long-term nutritional status compared with TG. Overall complications, other complications, and overall survival were not significantly different between the two groups. Moreover, subgroup analysis revealed that the occurrence of anastomotic strictures and reflux esophagitis was associated with the use of novel gastrointestinal tract (GI) anastomoses (double-tract reconstruction, jejunal interposition, and semi-embedded valve anastomosis) after PG. CONCLUSIONS: Based on the available evidence, we recommend that surgeons accept PG combined with multiple novel anastomoses as an optimal surgical approach in patients diagnosed with resectable Siewert type II/III AEG.

The efficacy and safety of 5-fluorouracil based adjuvant therapy in resected biliary tract cancer: A systematic review and meta-analysis.

OBJECTIVES: The adjuvant therapy (AT) for biliary tract cancer (BTC) patients after surgery has always been controversial. More therapeutic regimens and high-quality evidence were needed to evaluate AT's survival benefit further. Thus, this study was performed to investigate the efficacy and safety of the 5-fluorouracil (5-FU) regimen in resected BTC patients. METHODS: PubMed, Cochrane Library, Web of Science, and the Embase were systematically searched from inception to Feb.3, 2021, for eligible studies. The pooled analyses were performed using Review Manager, Stata, and SPSS software. RESULTS: A total of 9 trials involving 1339 participants were included in the meta-analysis. Resected BTC patients could significantly benefit from a 5-FU regimen (HR:0.51, 95%CI, 0.38-0.69, P<0.0001), regardless of gallbladder carcinoma (GBC) or cholangiocarcinoma (CCA). Moreover, both adjuvant chemotherapy (HR:0.61, 95%CI, 0.47-0.79, P=0.0003) and chemoradiotherapy (HR:0.35, 95%CI, 0.14-0.83, P=0.02) could significantly improve clinical survival of resected BTC patients than the surgery alone group. In the subgroup analyses, patients with node-positive (P=0.02) or vascular invasion disease (P=0.002) could better benefit from postoperative AT. CONCLUSION: This study provides the latest evidence to support the 5-FU regimen in resected BTC patients regardless of GBC or CCA. Furthermore, high-risk patients are more likely to benefit from it, such as node-positive or vascular invasion disease.

Clinical efficacy and safety of robot assisted surgery for choledochal cysts excisions: a systematic review and meta-analysis.

BACKGROUND: This study aimed to evaluate the safety and therapeutic effect of Robot-assisted surgery (RAS) for choledochal cysts (CCs) excisions. RESEARCH DESIGN AND METHODS: PubMed, EMBASE, Cochrane Library, Web of Science, CNKI, WanFang, VIP, and CBM were searched from database inception to 1 May 2022. The Newcastle-Ottawa scale (NOS) was used to conduct quality assessments, and RevMan (Version 5.4) was used to perform the meta-analysis. RESULTS: In all, 9 studies, involving 623 patients, were analyzed. RAS compared with LAS was associated with less intraoperative blood loss, shorter time to start solid diets, shorter postoperative hospital stay, and lower complications. There was no significant difference in operative time between the two groups, but the total costs were higher in RAS. Our subgroup analysis showed that RAS had significant advantages over LAS in the child group: minor bleeding, shorter length of hospital stay, and fewer postoperative complications. CONCLUSIONS: The available evidence indicates that the RAS system has the advantages of less intraoperative blood loss, minor tissue damage, quick recovery, and sound healing in treating choledochal cyst, which proves that the RAS is safely feasible. Especially in children, RAS tends to be a better choice.

Cost-Effectiveness of Dual Bronchodilator Indacaterol/Glycopyrronium for COPD Treatment in China.

BACKGROUND: Indacaterol/glycopyrronium (IND/GLY) is a once-daily dual bronchodilator for long-term treatment of patients with chronic obstructive pulmonary disease (COPD). The efficacy and safety of IND/GLY have been proved before, but the cost-effectiveness is unknown in China. PURPOSE: This study assessed cost-effectiveness of IND/GLY comparing with salmeterol/fluticasone (SAL/FLU) and tiotropium. METHODS: A patient-level simulation model was established from Chinese payer perspective. Patient parameters were randomly simulated through resampling from parameter distributions based on clinical trials and China-specific cost data to represent individual level health state and health state transitions in the model. We simulated patient-level health state, costs, life years (LYs) and quality-adjusted life years (QALYs) of whole life horizon to evaluate the cost-effectiveness of IND/GLY comparing with SAL/FLU and tiotropium respectively. RESULTS: Comparing with SAL/FLU, IND/GLY resulted in 0.384 LYs and 0.255 QALYs gained. The incremental cost-effectiveness ratio (ICER) is -35,822 CNY/LY and the incremental cost-utility ratio (ICUR) is -53,834 CNY/QALY for IND/GLY versus SAL/FLU. Comparing with tiotropium, IND/GLY resulted in 0.232 LYs and 0.146 QALYs gained. The ICER is 39,729 CNY/LY and the ICUR is 63,246 CNY/QALY for IND/GLY versus tiotropium. CONCLUSION: This study found that dual bronchodilator IND/GLY is cost-effective for stable COPD treatment in China from Chinese payer's perspective.

Efficacy and safety of preoperative biliary drainage in patients undergoing pancreaticoduodenectomy: an updated systematic review and meta-analysis.

OBJECTIVES: This study aimed to evaluate the effect of preoperative biliary drainage (PBD) on outcomes of pancreaticoduodenectomy (PD) in patients with biliary obstruction. METHODS: We searched PubMed, EMBASE, Cochrane library, and Web of Science from database inception to 11 March 2021. We used the ROBINS-I tool and Cochrane risk of bias tool 2.0 to assess the risk of bias. The data were statistically analyzed using the RevMan software (Version 5.4). RESULTS: In all, 43 studies, including 23,076 patients, were analyzed, of which 13,922 patients were treated with PBD and 9154 were treated with no preoperative biliary drainage (NPBD). The morbidity     , infection morbidity      , and postoperative pancreatic fistulae (POPF)       in patients undergoing PBD, were significantly higher than those in patients undergoing NPBD. Further, PBD may lead to a significantly worse 2- and 3-year overall survival (OS) rates           . In subgroup meta-analysis, the differences in morbidity, POPF, and OS outcomes lost significance between the PBD and NPBD groups when the mean total serum bilirubin (TSB) concentration was below 15 mg/dl. CONCLUSIONS: Routine PBD still cannot be recommended because it showed no beneficial effect on postoperative outcomes. However, in patients with < 15 mg/dl TSB concentration, PBD tends to be a better choice.

Incisional negative pressure wound therapy for clean-contaminated wounds in abdominal surgery: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: The role of incisional negative-pressure wound therapy (iNPWT) in preventing surgical site infections (SSIs) in clean-contaminated abdominal wounds is still controversial. This meta-analysis was performed to evaluate whether the use of iNPWT could reduce SSIs and other complications in clean-contaminated abdominal surgery. METHODS: The authors searched PubMed, EMBASE, Cochrane library, and Web of Science from database inception to 23 January 2021 for randomized controlled trials (RCTs). They assessed the risk of bias using the Cochrane Collaboration risk of bias tool and conducted a meta-analysis using RevMan 5.4. RESULTS: Eleven RCTs, including 4112 patients, were analyzed, of which 2057 were treated with iNPWT and 2055 with standard dressings. The SSI rates (OR = 0.76, 95% CI = 0.61-0.94, P = 0.01), in patients undergoing an iNPWT intervention were significantly lower than those in patients receiving standard dressings. There was no statistically significant difference between the rates of incision dehiscence, seroma, and readmission between groups. CONCLUSIONS: Application of iNPWT for clean-contaminated wounds in abdominal surgery reduced SSI rates but showed similar rates of wound dehiscence, seroma, and readmission compared with standard dressings.

T-tube or no T-tube for biliary tract reconstruction in orthotopic liver transplantation: an updated systematic review and meta-analysis.

Objectives: Biliary tract reconstruction with or without T-tube is commonly used in orthotopic liver transplantation (OLT). However, the efficacy and safety of T-tube usage remain controversial. This meta-analysis was conducted to assess the latest evidence of clinical outcomes.Methods: Embase, Cochrane Library, PubMed, and Web of Science were systematically searched from inception to 20 January 2021 for eligible studies. The analyses were performed using Review Manager and Stata.Results: A total of 24 trials involving 3320 participants were included in the meta-analysis. Compared with the no T-tube group, there was a higher incidence of overall biliary complications (OR:1.54; 95%CI, 1.06-2.24; P = 0.02), bile leaks (OR:2.34; 95%CI,1.57-3.48; P < 0.0001), cholangitis (OR:2.78; 95%CI,1.19-6.51; P = 0.002), and longer cold ischemia time (MD:22.27; 95%CI,0.80-43.74; P = 0.04) in the T-tube group. Furthermore, the no T-tube group had significantly higher odds of biliary strictures than the T-tube group (OR:0.60; 95%CI, 0.47-0.78; P = 0.0001).Conclusion: T-tube is still not routinely recommended, but is a good choice for OLT patients at high risk of biliary strictures. Notably, the higher rate of biliary complications in the T-tube group did not translate into an increase in endoscopic or re-operative interventions.