An increasing number of AB0-incompatible (AB0i) liver transplantations (LT) are being undertaken internationally in recent years due to organ shortages and the need for urgent transplantation. The aim of our study was establish the value of ABOi LT from available retrospective results of AB0i pediatric liver transplantations performed in European reference centers now belonging to the TransplantChild, European Reference Network (ERN). Data from medical records were analyzed, including demographic data, diagnosis, urgency of transplantation, time on the waiting list, PELD/MELD score, desensitization procedures, immunosuppression, selected post-transplant complications, and patient and graft survival. A total of 142 patients (pts) with transplants between 1986 and 2018 in 8 European transplant centers were included in the study. The indications for liver transplantation were: cholestatic diseases in 62 pts, acute liver failure in 42 pts, and other conditions in the remaining 38 pts. Sixty-six patients received grafts from living donors, and seventy-six received grafts from deceased donors. Both patient and graft survival were significantly affected by deceased donor type, urgent transplantation, and the development of vascular complications. In the multivariate analysis, vascular complications had a negative impact on patient and graft survival, while a longer time from the first AB0i LT in the study showed better results, suggesting an international learning experience. In conclusion, we believe that AB0i LT in children is now a safe procedure that may be adopted more readily in children. For more than 30 years, liver transplantation (LT) has been accepted as a major life-saving yet routine treatment for children with end-stage liver disease. This highly successful situation has led to an international situation of organ shortages that is especially critical for patients needing urgent transplantation. Therefore, a number of responses to the shortage have been adopted including marginal donors and donors with recipient-incompatible blood groups (AB0i).Starzl et al. were the first to report 11 cases of AB0i LT in 1979 ,3,4.It has been noted by several authors that the results of AB0i LT were better in the pediatric recipient population, particularly among the youngest children below 2 years of age, attributed to their immature immune system ,6.The aim of our study was to retrospectively review the experience of AB0i transplants in children in leading pediatric liver transplant centers of the TransplantChild, European Reference Network in Europe. We set out to review the indications, practices for pre- and post-transplant treatment, and the results of these transplantations with the inclusion of immunological and other complications to assess patients and graft survival as well as the factors influencing these results. We also wanted to assess if any progress has been made in the outcomes of AB0i LT in children over the study period and to consider the current situation with respect to the use of this organ source.Clinical material: data on 150 pts were collected from eight European transplant centers. Eight patients were excluded from the analysis due to a lack of sufficient data. The contributing centers were Children’s Memorial Health Institute, Warsaw, Poland (72 pts); ASST Hospital Papa Giovanni XXIII, Bergamo, Italy (2 pts); Hannover Medical School Children’s Hospital, Germany (12 pts); Karolinska University Hospital, Stockholm, Sweden (5 pts); King’s College Hospital, London, UK (23 pts); Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal (12 pts); La Paz University Hospital, Madrid, Spain (8 pts); and OspedalePediatrico Bambino Gesu, Roma, Italy (8 pts).Data from medical charts were analyzed, including demographic data, diagnosis, urgency of transplantation, time on the waiting list, PELD/MELD score, desensitization procedures, immunosuppression, vascular, biliary, rejection, CMV, PTLD and related post-transplant complications, and patient and graft survival. We also analyzed the results of AB0i LT according to recipient age (0–1 yr vs. older), and early and later periods of time were chosen on the basis of comparing equal numbers of patients in each period (1986–2010 vs. 2011–2018).t-test and Mann–Whitney U test were used to assess unpaired associations between continuous variables. The Chi-Square test was used to examine the differences between categorical variables. We also created Kaplan–Meier plots to analyze both patient and graft survival and compared them between groups using a log-rank test. A logistic regression analysis was used for the multivariate assessment of the relation between graft loss, recipient death, and the various predictor variables. Risk factors with a known or suspected clinical significance and a p-value less than 0.10 in the univariate analysis were included in the initial multivariable model. A p-value of less than 0.05 was considered statistically significant.The data were analyzed using Statistica 13.3 software, StatSoftinc . The analysis involved the assessment of baseline demographics and clinical data using median and ranges, and distributions for categorical variables. The Student This study was approved by the ethics committee at the Children’s Memorial Health Institute: decision number 30/KBE/2018 issued on 10 October 2018. All participant centers followed the required ethics requisites for transmission of anonymized data to the TransplantChild, European Reference Network.Upon analysis, 142 patients with transplants between 1986 and 2018 were included in this retrospective study. There were 67 boys and 75 girls. Their ages at transplantation ranged from 0.02 to 18 yrs (median 0.93 yrs). The indications for liver transplantation were biliary atresia and other cholestatic diseases in 62 pts (43.6%), acute liver failure in 42 children (29.6%), primary hepatic tumors in 8 pts (5.6%), other diseases in 15 pts (10.6%), and re-transplantation in 15 pts (10.6%).The transplantations were performed with grafts from 66 living and 76 deceased donors. The donor ages ranged between 0.17 and 76 yrs (median 28.2 yrs).Follow-up after transplantation in the entire study group was 1 day to 32 yrs, with a median 4.2 yrs and a mean 5.5 ± 5.4 yrs, and was limited in most cases to transition to adult care. Overall results: patient and graft survival are shown in We also compared the results of AB0i LT in infants up to one year old  and older than one year children . The demographic and clinical data of recipients and donors are presented in After transplantation, the only differences occurred in the rates of intrahepatic biliary stenosis and re-transplantation, both more common in Group 2. There was no significant difference in the rate of rejection, or patient or graft survival between the two groups, but more children survived due to re-transplantation among patients older than one year There was a clear trend towards an increased number of AB0i LT over the study period. Between 1986 and 2003, seven AB0i liver transplants were performed in the eight centers participating in the study; between 1997 and 2007, there were 36 AB0i LTs; and between 2008 and 2018, the number of AB0i transplants almost tripled, reaching 99 procedures. As the oldest group had few patients and some data are lacking, we divided the patients into two almost equal groups: 72 pts transplanted between 1986 and 2010 (Group 1) and 70 pts transplanted between 2011–2018 (Group 2) to compare if there was any change in patient and graft survival over time. The group characteristics and a comparison of the results are presented in In the multivariable analysis, only vascular complications and year since first AB0i LT were important for graft loss and patient death .The increasing success and utility of liver transplantations has been leading to increasingly more being undertaken internationally while organ donation is unchanged or falling, leading to an increasing discrepancy between the availability of grafts and the number of patients on waiting lists. Various responses have been developed: split liver transplantation, living donation, and wider acceptance of so-called marginal donors and grafts, including, as we described, grafts from AB0i donors. The acceptance of donor-recipient AB0 blood group incompatibility was initially limited largely to the extreme circumstances of patients with an urgent need for LT. The initial results were unsatisfactory, with high rates of rejection, HA thrombosis, biliary complications, sepsis, and other causes of graft and patient loss ,7,8,9,10Therefore, we aimed to consider the achievements of centers in Europe, to review current practices, and to set a benchmark for the use of this source of grafts for liver transplantation in children.During our study period, several protocols of pre-transplant desensitization were developed internationally in an attempt to prevent early or immediate humoral rejection and to improve late results after AB0i LT: splenectomy, plasma exchange, immunoadsorption, high-dose intravenous immunoglobulins (IVIG), and antiCD20 monoclonal antibodies (rituximab) ,16,17,18However, almost 30% of children were treated with IVIG postoperatively. Other methods of desensitization were used only occasionally both pre- and post-transplantation. As reported in the literature, pediatric immunosuppression protocols for AB0i liver transplant differ significantly between centers ,24,25,26When desensitization and immunosuppression between the two age groups were compared, children below 1 year of age received less immunosuppressive drugs after AB0i LT , which wIsoagglutinin levels increase with age from infancy so we expect less acute rejection episodes and severity in children below 1 year of age, particularly of the humoral type ,12,27,28It is recognized that patients receiving AB0i grafts are at increased risk of developing certain complications ,29,30,31Another common complication that may occur usually within the first 3 months after AB0i LT is damage to the intrahepatic bile ducts and development of multiple intrahepatic biliary stenosis. It may be caused by immunological insult by humoral reaction to the donor blood group antigens, which are present on the epithelium of bile ducts for 3–6 months after LT ,32,33. IThe overall patient and graft survival in our series is perhaps not as good as we wish, but our study period included children with transplants from as early as 1986. Comparing these results to those reported by the European Liver Transplant Registry (ELTR), for a similar period, the results in our series of AB0i LT are similar to all contemporaneous pediatric liver transplantations reported to the ELTR  34]..34].Although both patient and graft survival are better in younger children ,6, the dWe used a univariate analysis as a starting point for the creation of a multivariate logistic regression model to assess the relationship between graft loss, recipient death, and the various predictor variables. We showed that graft loss and recipient death were only related to two independent risk factors: vascular complications and time from first transplant, supporting the view that immunological reactions do not have a major influence on the results of AB0i LT in our particular pediatric populations.In summary, our study has shown that the outcome of AB0i liver transplantations in children has improved considerably over the last 20 years. The reasons for this improvement are probably multifactorial, including better perioperative and anesthetic management; better perioperative monitoring; increasing multidisciplinary experience and surgical skills; improved immunosuppression and understanding; and the prevention, diagnosis, and treatment of humoral rejection  ,36,37,38While there is a pressing need for expansion of the pediatric donor pool in response to a critical organ shortage, the improvement in the results of AB0i LT makes it justifiable to use this type of transplantation not only in circumstances of emergency transplantation due to acute liver failure and severe acute decompensation of chronic liver disease and semi-elective transplantation for primary hepatic tumors but also in elective transplantations, particularly from living related donors ,25,39,40


Agentic narcissism and vulnerable narcissism have been widely studied in relation to social media use. However, with research on communal narcissism in its early stages, the current study examines communal narcissism in relation to social media use. Specifically, the current study investigates whether communal narcissism is related to use and frequency of use of the popular social networking sites Instagram, Reddit and Twitter, and if communal narcissism relates to the importance of receiving feedback and to the quality-rating of self-presented content on those platforms. A total of 334 individuals were recruited from Amazon Mechanical Turk, with two-thirds being male (66.7%). A regression analysis showed that communal narcissism was related to increased use of Instagram and Twitter but not Reddit. Sharing content, the importance of feedback and better than average ratings had positive associations with communal narcissism. The relationship between communal narcissism and sharing on social media was fully mediated by wanting validation on social media and higher ratings of self-presented content. Communal narcissism had a notably strong relationship with wanting validation on all platforms and our results suggest that communal narcissism might be especially relevant in the context of social media use. Social media use has become a routine part of daily life for a large part of the population . The intNarcissism refers to entitlement, self-absorption, self-importance, grandiose expectations of oneself and a tendency for self-enhancement ,15,16,17Unsurprisingly, these shared narcissistic tendencies relate to some online behaviors . For exaTo date, agentic narcissism and online behaviors have been the most examined, followed by vulnerable narcissism , but litTherefore, as communal narcissism has been severely neglected from the literature on narcissistic tendencies and social media to date, it remains unknown if communal narcissistic behaviors and qualities apply in the online community as well. It is expected that communal narcissism will display a prominent relationship with social media use, as with other manifestations of narcissism , due to The focus of previous social media and narcissism studies has also largely been on Facebook use ,42,43,44The goal of this study was to examine the relationships between social media use and communal narcissism and assess the use of popular social media sites, which possessed visual, text-based and mixed content representation, to address previous gaps in the literature . First, Previous studies have explored narcissism and frequency of sharing ,48 and fTo demonstrate, 2f = 0.15, with statistical power (1 − β) = 0.95, and five predictors), a sample size of N = 138 was required [To find out the required sample size, a priori power analysis was conducted. Based on previous research ,29,30, arequired ,56. Participants in this study were 334 in total, with 66.7% male and 32.3% female. The age of the sample ranged from 18 to 74, with most participants reporting being aged 25 to 34 years old (48.8%). Most participants came from North America 57.5%), then Asia (19.5%), followed by Europe (9.9%), Latin America and the Caribbean (7.8%) and Middle East and Africa (5.1%). Originally, a total of 360 participants were recruited for the study, but 26 participants failed the quality control test of answering too quickly and thus were excluded, as established in previous studies .5%, then to ensurDemographic information. Participants were asked to indicate where they came from, their gender  and age, where the response options for age were 18–24, 25–34, 35–44, 45–54, 55–64, 65–74, 75–84 and 85 or older. very often) to 5 (never). Third, to determine need for validation, participants were asked how important it was for them to earn karma-points (Reddit), likes (Instagram) or likes/retweets (Twitter) on their posts, where the answers ranged from 1 (extremely important) to 5 . Lastly, participants were asked to rate the quality of their own social media content, where the answers were: far below average, moderately below average, slightly below average, average, slightly above average, moderately above average and far above average. Including the possibility to state “I do not share connect on Reddit/Instagram/Twitter”. Social media behavior. Participants were asked whether they used Reddit, Instagram or Twitter separately, and if the answer was yes (coded 1) compared to no (coded 0), more questions were displayed regarding their social media behavior on those sites. If the answer was no to use, they skipped the following question regarding that specific platform. If yes, participants were asked how frequently the platform was used. Secondly, how often they shared opinions (Reddit), self-pictures (Instagram) or images and posts (Twitter). The answer choices for the first two questions ranged from 1  to 7 (strongly disagree). The internal consistency in the current sample was good (α = 0.96). Narcissism. To measure communal narcissism, the Communal Narcissism Inventory (CNI) was used ,61. The I insist upon getting the respect that is due to me” or “I usually get the respect I deserve” [To measure agentic narcissism and control for its effects, the Narcissistic Personality Inventory 13-item scale (NPI−13) was used  which isdeserve” . The intI dislike sharing credit of an achievement with others” where answers ranged from 1 (very characteristic) to 5 (very uncharacteristic) [To measure vulnerable narcissism, the Hypersensitive Narcissism scale (HSNS) was used. The HSNS is a 10-items scale that includes statements such as: “eristic) ,65. The eristic) , narcisseristic) ,23,27. TTo analyze social media use, Pearson correlation coefficients were calculated  between The statistical package for social sciences (SPSS) was used for the analysis . Prior tTo test whether motives of using social media  mediated the relationship between narcissism and sharing on social media, we carried out a structural equation path model. The path model was tested using Mplus, version 6.12  using 50pr = 0.497, p < 0.01; between communal and vulnerable narcissism pr = 0.557, p < 0.01 and between communal and vulnerable narcissism pr = 0.480, p < 0.01. To explore the relationship between narcissism and social media use, Pearson correlation coefficients were examined. The results from the analysis are presented in A total of 87, 81, and 76% of participants responded as using Reddit, Instagram and Twitter, respectively see . The corAs To test whether communal narcissism predicted social media behaviors, in addition to agentic and vulnerable narcissism, we ran a logistic regression analysis see  and hierWhen controlling for demographics factors and agentic and vulnerable narcissism, communal narcissism was positively related to all the social media behaviors, except for Reddit use and frequency of use see . This suTo understand the mediating effects, all three narcissism variables, the motives and sharing were entered into a mediation analysis. p = 0.007) and quality . These social media motivators fully mediated the relationship between communal narcissism and sharing . In addition, there was a significant indirect effect from vulnerable narcissism to sharing through validation , which partially mediated the relationship between vulnerable narcissism and sharing . Narcissism explains a large amount of variance in validation (r2 = 0.631) and less variance in quality (r2 = 0.355). Together, narcissism and motives also explain variation in sharing well (r2 = 0.670).Significant indirect effects emerged from communal narcissism to sharing through both validation (z = 0.144, This study analyzed communal narcissism in relation to social media behavior and motives, with the intention of adding to the literature on communal narcissism within the online community. While agentic narcissism has been extensively covered in relation to online use, with vulnerable narcissism covered to some extent , communaIndividuals high on communal narcissism seemed at least as likely to use Instagram as individuals high on agentic narcissism, which might be comparable to previous studies that have found that agentic narcissists relate more strongly to visual social media ,38. In gAll things considered, communal narcissism is related to higher prosocial self-enhancement and is inherently rooted in communion . TherefoHowever, the three platforms examined possess different kinds of use, not solely related to visual or text-based representations. For example, Twitter is recognized for online activism ,71 and IThat being said, this study presented new findings regarding communal narcissism in the online community. Interestingly, as agentic narcissism has been mostly covered in the literature, these results indicated that communal narcissism displays strong relationships with social media use and specific behaviors as well, and motives for doing so. In addition, while displaying a preference for the visual platform Instagram, upon choosing another social networking site, sharing content, wanting validation and quality-ratings were just as prominent for text-based sites. Perhaps a visual format has a stronger appeal to narcissism, but narcissism does relate to certain behaviors upon choosing any platform, which is an interesting aspect for future studies. Furthermore, this study underlines the importance of properly separating the effects that different manifestations of narcissism can have on various behaviors, both online and in direct communication. More research in needed on communal narcissism in relation to social media use and other online behaviors. In addition, more research is needed to understand causal relationships of narcissism and social media use and a proper separation of different genders, age groups and cultures to generalize the overall effects.


PubMed, Web of Science, Embase, CNKI, and Wanfang databases were thoroughly searched for eligible studies, in which the relationship between SPHK1 expression and cancer prognosis was evaluated. Hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled to estimate the impact of SPHK1 expression on cancer patients' survival. Odds ratios (ORs) and 95% CIs were combined to assess the association between SPHK1 expression and clinicopathological characteristics of cancer patients. The certainty of evidence was evaluated by Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria. P < 0.001) and disease-free survival (DFS) . What is more, SPHK1 overexpression was significantly correlated with certain phenotypes of tumor aggressiveness, such as clinical stage , tumor invasion , lymph node metastasis , and distant metastasis . The quality of the evidence for both OS and DFS was low.  Thirty studies comprising 32 cohorts with 5965 patients were included in this meta-analysis. The outcomes indicated that elevated SPHK1 expression was associated with worse overall survival (OS) (HR = 1.71, 95% CI: 1.45-2.01,  Increased SPHK1 expression is related to poor prognosis in human cancers and may serve as a promising prognostic marker and therapeutic target for malignant patients. However, conclusions need to be treated with caution because of lack of high quality of evidence. Cancer is a serious public health problem, leading to a severe burden of disease in the world. According to a report released by GLOBOCAN in 2018, approximately 18.1 million people were newly diagnosed with cancer and 9.6 million people died of cancer, which was based on researches performed in 185 countries , 4. TherSphingolipids are a key component of cancer development due to their role in angiogenesis and lymphangiogenesis driven by cancer stem cells . Many reSPHK1 has been shown to be significantly upregulated in a variety of cancers, such as breast cancer , lung caIn accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, we performed a systematic literature search of PubMed, Web of Science, Embase, CNKI, and Wanfang databases to find relevant articles assessing the relationship between SPHK1 expression and prognosis of various malignant tumors. The following terms and their combinations are used as search keywords: (“sphingosine kinase 1” or “SPHK1”) AND (“immunohistochemistry” or “IHC”) AND  AND , covering all articles published in English and Chinese as of July 2021. In addition, we manually screened the reference lists of the retrieved articles to seek for additional eligible studies.Eligible articles in this meta-analysis were subject to the following inclusion criteria: (1) the publication investigated the relationship between SPHK1 expression and the prognosis  and disease-free survival (DFS)) of patients with solid tumors. (2) The expression of SPHK1 was detected in the primary cancer tissue by immunohistochemistry (IHC) stain and divided into “positive” and “negative” or “high” and “low” groups; and (3) hazard ratio (HR) and 95% confidence interval (CI) were readily available or could be calculated indirectly. Studies with any of the following flaws were excluded: (1) reviews, abstracts, letters, editorials, expert opinions, case reports, or animal experiments; (2) HR and 95% CI could not be obtained by sufficient information or data; and (3) studies with a sample size of less than 50.The data extraction in this meta-analysis was independently completed by two investigators (XSS and ZCM) independently using a standardized data-extract form and any divergence was adjudicated through discussion. The following data were collected: first author's name, publication year and language, study region, duration time, cancer type, sample size, follow-up time, detection method, cut-off value, number and proportion of patients with high SPHK1 expression, survival data, analysis method, and clinicopathological characteristics. If both univariate and multivariate analyses were used to calculate the HR for OS or DFS, the latter was preferred because the result was adjusted for confounding factors and was more accurate . For theThe quality of each included cohort study was independently assessed using the Newcastle-Quality Assessment Scale (NOS). According to the NOS scale, the quality of the cohort study is judged based on three contents: selection of the exposed and unexposed cohort (4 points), comparability of the two cohorts (2 points), and outcome assessment (3 points) . Studieshttp://gradepro.org.The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method was applied to evaluate the quality of the evidence , 48. TheQ and I-squared statistical tests, in which P < 0.05 or I2 ≥ 50% was considered significant heterogeneity [P < 0.05 was considered statistically significant.HRs and their 95% CIs were combined to estimate the effect of SPHK1 expression on survival. ORs and their 95% CIs were pooled to assess the association between SPHK1 expression and clinicopathological features. The heterogeneity was evaluated using Cochran's ogeneity . If publThe literature search flow diagram is presented in The main characteristics of the 32 eligible cohorts are summarized in P < 0.001) using the random-effects model because of heterogeneity  (P < 0.001), urinary system cancers , head and neck cancers , and LC , but no significant relationship was observed in patients with reproductive system tumors  and BC . In term of sample size, SPHK1 positive expression was significantly associated with poor OS in the subgroups with large  and small  sample sizes. With regard to the proportion of patients with high SPHK1 expression, high SPHK1 expression predicted shorter OS in both high  and low  proportion subgroups. Similarly, SPHK1 overexpression was associated with poor OS in the subgroup of analysis method. Thus, almost all subgroup analyses showed that SPHK1 positive expression was associated with poor OS, which to some extent indicates the prognostic value of SPHK1 for tumors and the stability of the results of this study.As shown in < 0.001) . To furtI2 = 57.3%, P = 0.009), the random model was applied and a significant association was observed between increased SPHK1 expression and poor DFS of cancer patients   .P < 0.001). Similar results showed that high SPHK1 expression was significantly associated with tumor invasion (T1-T2 vs. T3-T4) , lymph node metastasis (negative vs. positive) , and distant metastasis (negative vs. positive) . This obvious association was not observed in age (young vs. old) , gender  , and tumor size  .The relationship between SPHK1 expression and clinicopathological features is shown in Sensitivity analysis was conducted to evaluate the influence of each cohort on the meta-analysis results of OS by omitting one cohort in turn. The results confirmed the robustness and reliability about the prognostic value of high SPHK1 expression on unfavorable OS . SimilarP < 0.001), while the P value of the Bgger's test was greater than 0.05 (P = 0.399). Thus, the trim and fill method was used. Nine missing cohorts were needed to fill into the funnel plot (P < 0.001) still showed the significant relationship between SPHK1 overexpression and worse OS, indicating the reliability of our results. In addition, there was no potential publication bias for DFS   .The GRADE method was adopted to assess the certainty of the evidence. The results indicated that the quality of the evidence for both OS and DFS was low . Thus, oP < 0.001) and DFS  in various tumors. Moreover, sensitivity analysis and publication reinforced the stableness and reliability of the meta-analysis results. However, the quality of the evidence for both OS and DFS was low due to observational studies and heterogeneity. In addition, in order to further study the prognostic value of SPHK1 in solid tumors, we analyzed the relationship between SPHK1 and clinicopathological features that are also related to the prognosis of cancer patients. The pooled results demonstrated that SPHK1 overexpression was significantly related to clinical stage, tumor invasion, lymph node metastasis, and distant metastasis. Therefore, increased SPHK1 expression may be statistically associated with poor prognosis in cancer patients, although the certainty of evidence is low.To date, some original articles have studied the prognostic significance of SPHK1 in solid tumors, and both significant and insignificant studies have emphasized the importance of SPHK1 for survival, so it is necessary to quantitatively summarize the survival results. The current meta-analysis included 32 cohorts with 5965 patients, and the systematically evaluated outcomes indicated that high SPHK1 expression was significantly associated with poor OS  is originally a developmental procedure that has been used by tumor cells to promote their migration, invasion, and eventually colonization at a distance, resulting in distant metastasis, which leads to a poor prognosis of cancer patients . Loss ofThus, this study demonstrated that high immunohistochemical expression of SPHK1 in cancer tissues may be associated with poor survival in human solid tumor patients, which will promote the development of a novel biomarker for the diagnosis and prognosis and targeted therapy of solid tumors. First of all, in addition to biopsy or surgical tissue, further research on whether this important marker is also detectable in other forms of patient samples, such as blood, will be very important for the early detection and diagnosis of tumors . Second,Apart from the inspiring results, several limitations still should be noted in this quantitative meta-analysis. First, the population of the included studies was mainly concentrated in Asia, which affected the applicability of the results to some extent. Second, the inconsistent cut-off values for distinguishing between high and low expression of SPHK1 and the different analysis methods for evaluating the correlation between SPHK1 overexpression and prognosis may lead to different results of the included studies. Third, all of the included studies were retrospective cohort studies, in which positive results are more likely to be published than negative results. Fourth, as some studies did not directly provide the HRs, we had to estimate the HRs and 95% CIs from the survival curves, which may cause some errors. Fifth, the publication bias of this study is a concern because articles with positive results are more likely to be published, which may exaggerate the connection between SPHK1 expression and adverse outcomes. Sixth, the quality of the evidence for both OS and DFS was low, which affected our confidence in the estimation of the effect. Finally, this meta-analysis was not prospectively registered in international prospective register of systematic reviews (PROSPERO) that can help reduce selective reporting of outcomes .In summary, high SPHK1 expression was associated with poor prognosis and served as a useful prognostic biomarker, which might be a promising therapeutic target for solid tumors. However, conclusions need to be treated with caution because of lack of high quality of evidence.


To summarize the safety and effectiveness of high flow extracranial to intracranial saphenous vein bypass grafting in the treatment of complex intracranial aneurysms.The data of complex intracranial aneurysms patients for high flow extracranial to intracranial saphenous vein bypass grafting from January 2008 to January 2020 were retrospectively collected and analyzed. Eighty-two patients (31 men and 51 women) with 89 aneurysms underwent 82 saphenous vein bypass grafts followed by immediate parent vessel occlusion. The aneurysm was located at the internal carotid artery, middle cerebral artery, and basilar artery in 75, 11, and 3 cases, respectively.The patency rate of bypass grafting was 100, 100, 96.3 and 92.4% on intraoperation, on the first postoperative day, at discharge and 6 months follow-up, respectively. At discharge and 6 months follow-up, 3 and 6 patients had graft occlusions. The main postoperative complications were transient hemiparesis and hemianopsia. 3 patients died due to bypass complications and poor physical condition.High flow extracranial to intracranial saphenous vein bypass grafting is safe and effective in the treatment of complex intracranial aneurysms and the saphenous vein can meet the requirements of brain blood supply. A high rate of graft patency and adequate cerebral blood flow can be achieved.A single-centre long-term retrospective study was conducted to assess the safety and effectiveness of high flow EC-IC saphenous vein bypass grafting in the treatment of complex intracranial aneurysms. The data of 82 patients from January 2008 to January 2020 were retrospectively collected and analysed.We found the patency rate of bypass grafting was 100, 100, 96.3 and 92.4% on intraoperation, on the first postoperative day, at discharge and 6 months follow-up, respectively. At discharge and 6 months follow-up, 3 and 6 patients had graft occlusions.Finally, we conclude that high flow extracranial to intracranial saphenous vein bypass grafting is safe and effective in the treatment of complex intracranial aneurysms and the selected blood supply vessels can meet the requirements of blood supply.As far as we know, this study is one of the maximum number of cases in the treatment of complex intracranial aneurysms with saphenous vein bypass. Intracranial aneurysms, as a common cerebrovascular disease in neurosurgery, when treatment is indicated, are either treated by microsurgery or endovascular techniques. Both treatment options include several techniques and strategies . HoweverIn 1969, Yasargil  performeIn this study, the safety and effectiveness of high flow EC-IC saphenous vein bypass grafting for the treatment of complex intracranial aneurysms is illustrated in a single-center retrospective cohort of patients with long-term follow-up.In this study, the data of complex intracranial aneurysm patients for high flow EC-IC saphenous vein bypass grafting from January 2008 to January 2020 were retrospectively collected and analyzed. Basic demographics, aneurysm location social, preoperative clinical presentation, surgical outcomes, complications and follow-up information were recorded.The choice of surgical technique was made by the responsible consultant. The Institutional Review Board (IRB) of Zhongnan Hospital of Wuhan University approved this study. The IRB waived the need for written consent. All patient data were anonymized and deidentified prior to analysis.Digital subtraction angiography  with 89 aneurysms underwent 82 saphenous vein bypass grafts followed by immediate parent vessel occlusion. The aneurysm was located at the internal carotid artery, middle cerebral artery, and basilar artery in 75, 11, and 3 cases, respectively. The average diameter of aneurysm was 32.3 (24–52) mm. The main preoperative clinical presentation were nervous system symptoms. The above information can be found in Table The patency rate of bypass grafting, as confirmed by CTA or DSA, was 100, 100, 96.3 and 92.4% on intraoperation, on the first postoperative day, at discharge and 6 months follow-up, respectively. At discharge and 6 months follow-up, 3 and 6 patients had graft occlusions (Table The main postoperative complications were transient hemiparesis (6/82 (7.3%)) and hemianopsia (2/82 (2.4%)). For the 6 patients with transient hemiplegia, the postoperative muscle strength was grade II-III and recovered to IV-V grade at 7–10 days later, small infarction in basal ganglia area was found by CT. 3 patients died due to bypass complications (1 patient) and poor physical condition (2 patients)  Table .For surgical clipping or endovascular coiling, complex intracranial aneurysms are unique and complex challenges. High flow EC-IC bypass grafting can solve this problem well –10. As fWe got considerable results in this study, the patency rate of bypass grafting was 100, 100, 96.3 and 92.4% on intraoperation, on the first postoperative day, at discharge and 6 months follow-up, respectively. The results of this study are similar to those of other previous studies –12. So, The indications for high flow EC-IC saphenous vein bypass grafting were these: large and complex aneurysms, aneurysms with a large and complex neck not suitable for clip reconstruction, blister aneurysms, dissecting aneurysms, dissecting aneurysms, aneurysms with an origin of branch vessel(s) from the aneurysm sac, calcification or atherosclerotic changes of the aneurysm neck, extensive thrombosis inside the aneurysm, and recurrent aneurysms that had failed endovascular or microsurgical treatment .About ruptured and unruptured aneurysm, we think whether the aneurysm is ruptured or not, we should carry out surgical treatment as soon as possible as soon as the patient’s vital signs are stable. Especially, for the huge and complex ones. And SAH or intracranial hematoma can also be cleared by surgical treatment.In the past, there has always been a question, when to isolate the aneurysm? Is it isolated directly during the operation or after CTA or DSA confirms that the blood vessels are unobstructed? However, the emergence of hybrid operating room, which has both interventional radiology and surgical equipment, has greatly solved this problem. After microsurgery, DSA was performed directly (in the same operating room) to evaluate whether the blood vessels were unobstructed or not as soon as possible. Therefore, in the future, we encourage the operation in hybrid operating room. It makes the intraoperative vascular evaluation more effective. After the establishment of the hybrid operating room in our center in 2017, the operation is carried out in it. In addition to the intraoperative DSA can be used to evaluate the patency of blood vessels, the intraoperative fluorescein angiography and ultrasound can also be used. In fluorescein angiography, indocyanine green was used to show the blood vessels under the microscope. Ultrasound uses a probe to monitor the patency of blood vessels. Actually, all three have similar functions.High flow extracranial to intracranial saphenous vein bypass grafting is safe and effective in the treatment of complex intracranial aneurysms and the saphenous vein can meet the requirements of blood supply. A high rate of graft patency and adequate cerebral blood flow can be achieved.


During recent years, the integration of technology has substantially improved self-reported dietary assessment methods, such as food frequency questionnaires (FFQ), food records, and 24-h recalls. To further reduce measurement error, additional innovations are urgently needed. Memory-related measurement error is one of the aspects that warrants attention, which is where new smartphone technologies and ecological momentary assessment (EMA) approaches provide a unique opportunity. In this article, we describe the DIASS study, which was designed to evaluate an innovative 2-h recall (2hR) smartphone-based methodology, against traditional 24-h recalls, FFQ, and biomarkers, to assess both actual and habitual dietary intake. It is hypothesized that a 2-h reporting window decreases reliance on memory and reporting burden, and increases data accuracy. We included 215 men (28%) and women (72%), with a mean ± SD age of 39 ± 19 years and a mean ± SD BMI of 23.8 ± 4.0. Most participants were highly educated (58%). Response rates for the various dietary assessment methods were >90%. Besides the evaluation of the accuracy, usability, and perceived burden of the 2hR methodology, the study set-up also allows for (further) evaluation of the other administrated dietary assessment tools. Accurate dietary assessment is one of the essential aspects of nutrition and health (behavior) research, where 24-h recalls (24hRs), food frequency questionnaires (FFQs), and food records are currently the most commonly-used dietary assessment methods ,2,3,4. HAccordingly, there is a growing interest in more technology-based dietary assessment methods, which have the potential to improve accuracy and reduce the burden on both participant and researcher ,11,12. NTo the best of our knowledge, no  recall-based dietary assessment apps exist at present . AlthougTherefore, we developed an innovative smartphone-based dietary assessment app  that canAlthough the 2hR methodology sounds promising, its validation against established methods is imperative, to judge its actual value. The DIASS study was designed to evaluate the accuracy of the smartphone-based 2hR methodology, to assess both actual and habitual intake of food groups, energy, and nutrients compared to established methods and independent biological markers. Secondary aims included the evaluation of the usability, perceived burden, and compliance of the 2hR method compared to established methods. Additionally, the DIASS study allows further evaluation of the other administrated dietary assessment tools. With this article, we aim to provide an overview of the (1) study design of the DIASS study, and (2) baseline characteristics of the study population, as a reference for future evaluation studies that will be performed using these data.The DIASS study had a cross-over design (12-weeks), with two experimental conditions; i.e., measuring actual intake and habitual intake. Dietary intake was assessed by means of the new 2hR app, as well as various established methods. In addition, information on demographics  was collected by means of an online questionnaire derived from the NQplus questionnaire . AdditioOriginally, the 215 participants were randomly allocated into six groups . Groups After randomization in week 1, each participant completed two study periods of four weeks each , during which, either actual or habitual intake was assessed, in random order. To minimize the participant burden, and as such optimize compliance, the two study periods were separated by a wash-out period of two weeks . Additionally, overall diet quality was assessed in week 12.The DIASS study was approved by the ethics committee of Wageningen University and Research (WUR) (ABR No.: NL69065.081.19) and conducted according to the guidelines laid down in the Declaration of Helsinki.Recruitment took place between June 2019 and May 2020, and aimed to include 220 Dutch adults (men and women) aged 18–70 years. Eventually, 215 men and women were included in the study. Participants were recruited via the research volunteer database of the division of Human Nutrition and Health of WUR, social media accounts of the division , and through flyers and posters. Participants had to be Dutch speaking, not visually impaired, in possession of a smartphone with internet plan, metabolically stable , willing to maintain current dietary habits for the duration of the study, not participating in another dietary intervention study, not an employee of the division, and not having any formal training in the field of nutrition. Written informed consent was obtained from all participants prior to participation.Actual food intake was assessed on random non-consecutive days over one of the four-week study periods. Within this period, participants were invited to complete three 2hR-days and three 24hRs. In addition, a random subsample of 69 participants also provided four 24-h urine samples and two fasting blood samples. The urine collections were intentionally coupled to the recall days . Blood sampling occurred following two of the urine collections while the participants were at the study center to hand in their urine containers. During the other four-week study period, habitual food intake was assessed by random 2hRs. The same number of 2hRs was used as for the 2hR-days. However, to assess habitual intake, the 2hRs were randomly distributed over the four-week period . In case of non-response, the 2hR was automatically rescheduled on the same time on another day. In addition, at the end of the study period, participants were invited to complete a FFQ. In the final study week, participants were invited to complete an additional short FFQ, to assess overall diet quality.®, a dietary assessment app developed by WUR [®, participants were able to report their food intake of the previous 2 h. The food intake report screen is supported by an extensive food list, based on the Dutch Food Composition Database [The 2hRs were sent via Traqqd by WUR . By clicDatabase . FollowiDatabase  or amounDatabase .Actual intake was measured on thee random days by means of multiple consecutive 2hRs per day . A subsaHabitual intake was measured by multiple random 2hRs. Participants received an invitation on random days and times to report their food intake during the previous 2 h . The sam®. Items can be searched for in the food list, and consumed amounts can be reported in similar household measures, standard portion sizes, or in grams [®. Moreover, participants were able to make notes for clarifications. Invites for the web-based 24hRs were sent via email at 06:00 in the morning of the recall day. The questionnaire was accessible until midnight that same day. In case of non-response, a new 24hR was randomly scheduled.A total of 168 participants were invited to complete thee random web-based 24hRs with Compl-eat™. A subsample of 38 of these participants also collected 24-h urine samples. Consequently, for this group, two of the 24hRs were randomly scheduled and then communicated to the participant to ensure 24-h urine collection on the recall day. The remaining 24hR was unannounced. Compl-eat™ is a validated self-administered web-based dietary 24hR-tool developed by WUR and is based on the automated five-step multiple-pass method . In thisin grams ,22. CompA subsample of 39 participants were asked to complete interviewer-administered telephone-based 24hRs instead of web-based 24hRs. A subsample of 28 of these participants also collected 24-h urine samples. Therefore, two of the 24hRs were randomly scheduled and then communicated to the participant to ensure 24-h urine collection on the recall day. The final 24hR remained unannounced. If needed, the dieticians made multiple attempts to reach the participant by phone on a recall day. In case of non-response, a new 24hR was randomly scheduled.Since the validation of Compl-eat™, improvements have been made to the tool that still need to be validated. Therefore, the telephone-based 24hRs were used to ensure the accuracy of Compl-eat™. The telephone-based 24hRs were conducted by trained dieticians using a standardized protocol and the five-step multiple-pass approach . HoweverData from both the 2hRs and the 24hRs were entered in the computation module of Compl-eat™ . Total iAll participants were asked to complete a validated 183-item semi-quantitative FFQ, with a reference period of four weeks . This exAll participants were asked to complete the Eetscore™ in the final study week. The Eetscore™ is a self-administered web-based screener for diet quality . It consA total of 66 participants provided four 24-h urine samples during the ‘actual intake’ period. Two of these samples were linked to 2hR-days and the other two to 24hRs. The participants were instructed on 24-h urine sampling according to a standardized protocol and were provided with three-liter containers containing the preservative lithium dihydrogenphosphate (25 g). Participants also received three 100 mg para-aminobenzoic (PABA) tablets , and were instructed to ingest one PABA tablet with each main meal. The 24-h urine collection started with the second voiding after waking up and was completed with the first voiding after waking up the next day. Participants were instructed to record the beginning and end times of the 24-h urine collection, the time of ingesting the PABA tablets, and any possible deviations from the protocol . Urine samples were handed in at the study center where they were mixed, weighed, aliquoted, and stored at −80 °C until further analysis.PABA was provided to check for completeness of the 24-h urine samples. Research has shown that providing PABA is recommended, but that it does not necessarily have to be analyzed ; often cThe 24-h urine samples were assessed on nitrogen, potassium, and sodium content, which were used to estimate absolute intakes of protein, potassium, and sodium, respectively ,31. Urinn-3 fatty acid concentrations, to estimate habitual intake of fruit and vegetables, folate, and fish, respectively [The 66 participants that provided 24-h urine samples also provided two fasting blood samples. Following a 10-h overnight fast, these participants underwent a venipuncture at the study center. The venipunctures were conducted by experienced staff members and scheduled on days that participants were already at the study center to hand in their 24-h urine samples, sparing them extra visits. Biochemical analyses were performed either on a Dimension Vista 1500 automated analyzer  or a Roche Modular P800 chemistry analyzer . The blood samples were used to assess carotenoid, folate and ectively ,33,34. TAnthropometrics were conducted by trained staff, according to a standardized protocol in study week 1. Height was measured without shoes, using a stadiometer  to the nearest 0.1 cm. Weight was measured without shoes, heavy clothing, and with empty pockets on a digital scale  to the nearest 0.1 kg. Weight measurements were repeated in study weeks 7 and 12, to determine weight stability.Total energy expenditure (TEE) is estimated by calculating basal metabolic rate (BMR) and assessing physical activity level (PAL). BMR was calculated using the Harris and Benedict equation . In addiThe raw accelerometer data was downloaded from the ActiGraph devices and thoroughly checked by an experienced data scientist. Participants were included if the devices collected accelerometer data of 7 consecutive days. Next, the data were imported into ActiLife version 6.13.4 , and participant’s percentage of time spent in sedentary, light, moderate, vigorous, and very vigorous activity using the Troiano algorithm . The dayThe baseline questionnaire acquired general participant information . This questionnaire was derived from the NQplus study, a large cohort study in the Netherlands . AdditioIn the final study week, participants completed an evaluation questionnaire on their experiences using the app and various commonly-used conventional dietary assessment methods. The evaluation questionnaire was based on previous studies and assessed aspects such as ease of use, convenience, perceived reporting burden, perceived accuracy, likelihood of future use, and overall experience ,41. Respn) with percentages (%). The SUS score was calculated with a predefined formula (range 0–100). A SUS score of >68/100 indicates an above-average usability and a score of >80/100 indicates an excellent usability [Baseline characteristics are presented as means with standard deviations (SD) and frequencies (sability . Data an2. According to the accelerometer data the participants had a sedentary lifestyle (mean ± SD PAL of 1.46 ± 0.02). The majority of the participant were either <25 years (42%) or ≥50 years (38%), most of the participants were highly educated (58%), the majority of the participants were either married/registered partners (32%) or single (42%), over half of the participants (52%) had a paid job, and the majority of the participants did not follow a diet regimen (71%). Overall, response rates for the dietary assessment methods were high (>90%). The completeness of the urine collections was 86%, and 100% of the fasting blood samples were collected. Finally, mean SUS score of the app was 72 ± 14.In total, 215 men (28%) and women (62%) were included in the DIASS study . The parWe have described the design of the DIASS study, which aimed to evaluate a newly developed smartphone-based dietary assessment methodology against established methods and objective markers. A total of 215 men and women were included (18–70 years); mainly women and highly educated. The overall response rates were high with >90% for the dietary assessment approaches and >86% for the collection of biological samples.®, most of these apps rely on text entry for food identification and quantification; respondents select consumed foods from a fixed food list and quantify amounts by weights or household measures [Various dietary assessment apps have been developed for research purposes, all based on the food record approach. Similarly to Traqqmeasures ,46,47,48measures ,49,50,51measures ,43,48. Tmeasures . Howevermeasures ,43,48. Dmeasures ,31, biommeasures . Therefomeasures . MoreoveThe SUS score of 72 indicates that the app Traqq® has a good usability. This SUS rating was slightly lower compared to our prior usability test (mean SUS of 79) . HoweverThe DIASS study may be considered limited by the fact that about 70% of the participants were highly educated women, which may limit the generalizability of the results. However, this validation study was designed to assess the accuracy of the 2hR-based dietary intake estimates. Therefore, the lack of generalizability may not be as much of a limitation as it would have been in research into diet–disease relationships. However, acceptability and usability levels might be lower for individuals with a lower educational level ,56. TherUnfortunately, the COVID-19 pandemic forced us to cancel the final blood and urine collections, to safeguard the participants’ health. This decreased the number of participants that collected independent biomarkers, from 100 to 69 participants. However, the data from the remaining participants in this subsample still provide valuable insights into the relation between true and assessed intake. Although this last sample of participants were in lockdown for the entire study duration, the self-reported dietary assessment and additional measures could proceed as planned.In conclusion, the most important feature of the DIASS study is its elaborate study design. The results consist of actual dietary intake data obtained by multiple 2hR-days, multiple web-based or telephone-based 24hRs, and biochemical markers. This allows validation of actual intake assessment with the 2hR-days against both established methods and independent urinary biomarkers. Moreover, the same data can also be used to validate the most recent version of Compl-eat™. In contrast, the habitual dietary intake data obtained by multiple random 2hRs, FFQ, and, again, biochemical markers allows for validation of habitual intake assessment. This data also allow for further validation of the FFQ. Finally, the results of the Eetscore™ can be validated against the results of the FFQ and the 24hRs, as the diet quality score used in the Eetscore™ can also be calculated from these more extensive approaches. Additionally, the collected data can also be used to evaluate all administered methods, in terms of usability, response time, and perceived burden. As such, we believe that the DIASS study offers a unique opportunity for extensive evaluation of a variety of dietary assessment methods and contributes to the further improvements of these methods.


Background: A major source of noise pollution is traffic. In Germany, the SARS-CoV-2 lockdown caused a substantial decrease in mobility, possibly affecting noise levels. The aim is to analyze the effects of the lockdown measures on noise levels in the densely populated Ruhr Area. We focus on the analysis of noise levels before and during lockdown considering different land use types, weekdays, and time of day. Methods: We used data from 22 automatic sound devices of the SALVE  project, running since 2019 in Bochum, Germany. We performed a pre/during lockdown comparison of A-weighted equivalent continuous sound pressure levels. The study period includes five weeks before and five weeks during the SARS-CoV-2 induced administrative lockdown measures starting on 16 March 2020. We stratified our data by land use category (LUC), days of the week, and daytime. Results: We observed highest noise levels pre-lockdown in the ‘main street’ and ‘commercial areas’ (68.4 ± 6.7 dB resp. 61.0 ± 8.0 dB), while in ‘urban forests’ they were lowest (50.9 ± 6.6 dB). A distinct mean overall noise reduction of 5.1 dB took place, with noise reductions occurring in each LUC. However, the magnitude of noise levels differed considerably between the categories. Weakest noise reductions were found in the ‘main street’ (3.9 dB), and strongest in the ‘urban forest’, ‘green space’, and ‘residential area’ (5.9 dB each). Conclusions: Our results are in line with studies from European cities. Strikingly, all studies report noise reductions of about 5 dB. Aiming at a transformation to a health-promoting urban mobility can be a promising approach to mitigating health risks of noise in cities. Overall, the experiences currently generated by the pandemic offer data for best practices and policies for the development of healthy urban transportation—the effects of a lower traffic and more tranquil world were experienced firsthand by people during this time. The World Health Organization (WHO) declared the global spread of SARS-CoV-2 causing the coronavirus disease COVID-19) a pandemic on 11 March 2020 9 a pande. AccordiDespite the dire consequences of the pandemic, however, the deeply profound measures happened to allow for natural experiments that would otherwise simply not be feasible. One of these options is the possibility to measure the effects of reduced mobility, in particular road, railway, and air traffic, on noise levels in urban areas. As environmental noise is one of the most important environmental health risks, with many people being affected ,6, noiseIn Germany, the reduction of economic, human, and social activity has been reflected in a reduced volume of car, rail, and air traffic ,8,9, whiFirst studies using recorded sound pressure levels could demonstrate on average a decrease of 5 dB(A), reflecting the generally perceived noise reduction ,14,15,16The aim of our study is to describe the effects of the societal lockdown in Germany on noise levels in the city of Bochum, located in the densely populated and highly trafficked metropolitan Ruhr Area. Here, we focus on the analysis of noise levels before and during lockdown measures considering (i) different land use types in Bochum, (ii) weekdays and weekends, and (iii) time of day.For our analyses, we used the comprehensive data sets of the SALVE  project . The SALwww.rki.de/EN/Home/homepage_node.html, accessed on 22 April 2021). However, as these were recommendations, travel to work was still permissible  provided by the Regional Association for the Ruhr Area . To bettAhead of our analyses, we checked our data for plausibility. We investigated the sound pressure levels for outliers, checking manually for definitive methodical failures that clearly distort the sound analyses. In these cases, we excluded parts of the dataset accordingly. Aeq, using the software Kaleidoscope Pro [Aeq of all devices by day . Using the LAeq,24h we describe the mean course of the noise levels for each day over the observation period as well as patterns of specific weekdays. Calculating the mean LAeq of all devices for each of the two five-week periods pre- and during lockdown , we conduct this pre–during comparison. To compare weekdays with weekends, we calculated the mean LAeq of all devices separately for weekdays (Monday to Friday), Saturdays, and Sundays . Lastly, we calculated the daily mean LAeq per hour for all devices  to analyze specific daytime differences. Unless otherwise noted, we performed statistical analyses using IBM SPSS Statistics 27.0.0.0.We performed descriptive analyses calculating means and respective standard deviations. Differences between the pre- and during lockdown phases were calculated as Δ = cope Pro . We calcAeq,24h during the observation period. Despite a high variance of the recordings, the course depicts a clear drop of the mean overall LAeq, interestingly already starting before the administrative resolve. This early drop of the noise levels might be explained by press releases and intensive discussions on social media and TV about upcoming lockdown measures as already performed in other countries, i.e., in China. Furthermore, the health department of the city of Bochum recommended contact reductions as early as on 26 February 2020. Concerns of being infected and subsequent voluntary measures such as staying at home or using a home office started to reduced mobility prior administrative measures  of 58.0 dB pre-lockdown and 52.9 dB during lockdown  and weekdays (58.3 dB), whereas Saturdays were found to be the quietest days of the week (56.6 dB). In contrast, a different pattern emerges during lockdown, with Sundays being the quietest day of the week with low 51.5 dB (SD ± 8.3), followed by Saturdays (52.8 dB) and weekdays (53.2 dB). Overall, strongest reductions of the overall noise level between pre- and during lockdown are measured on Sundays (6.5 dB) and the weakest on Saturdays (3.8 dB).Aeq,1h) is presented in The overall course of mean noise levels of the pre- and during lockdown observation period by hourly time of day  and 5.3 dB(A). Noise reductions in neighborhoods turned out to be even higher, ranging between 6–20 dB(A). The “Observatoire de l’environnement sonore de la Métropole de Lyon” reports results of 21 recording stations in five French cities . They compared recordings 54 days during lockdown  and 69 days during a reference period lasting from 6 January 2020, to March 13, 2020 [DEN ranging on average between 4 and 6 dB(A); however, detailed descriptions of the time frame and the types of the selected locations are not provided. Data of 31 recording stations provided by the city council of Madrid, Spain revealed an average LDEN reduction of around 5 dB(A) during the lockdown period  compared to the reference period  [Aeq reduction of 5.4 dB at 11 measurement points during lockdown in spring 2020 compared to recordings at the same locations from spring 2019 [Aeq levels ranging between 1 to 10 dB. In Dublin, Ireland, Basu et al. (2020) [DEN reduction of about 6 dB(A) compared to the same period in 2019 [Aeq reduction in the city of Stockholm, Sweden, of 2–3 dB, depending on the weekday. The other one from the United States measured an overall reduction of about 2.6 dB(A). However, this study used the data of individual noise exposures assessed by smartwatches and headphones of 5894 participants [Comparing previous studies from different European cities investigating the effects of lockdown measures on noise levels, it is striking that all studies report noise reductions in a very similar order of magnitude of 5 dB(A). Thus, our result fits well into this surprising observation. For instance, Bruitparif (2020) compared a 15-week lockdown lasting from 16 March 2020, to 28 June 2020, with a 14-month pre-lockdown reference period lasting from 1 January 2019, to 29 February 2020, in Paris, France . They re in 2019 . To our icipants . The stuOn the other hand, to date there is only one study reporting distinctly higher noise reductions ranging between 20 and 30 dB(A) at four tourist locations in Granada, Spain . HoweverOur results reveal an interesting temporal course of the overall noise decrease. The noise levels obviously started to drop as early as mid-February, however, with further decreasing levels when the lockdown measures come into force. This early decrease might be due to the situation that, in Germany, discussion about the new SARS-CoV-2 started as early as February, and voluntary restrictions, like increased use of home offices, were successively carried out by parts of the population even before the official measures were taken. The marked reductions in noise during lockdown measures in Germany may be caused by a substantial decrease in mobility. Dance and McIntyre (2021)  observedNoise reduction due to the dramatically reduced air traffic is, however, another important effect of the measures. In Germany, air traffic has experienced a reduction of up to 60% . The numA further noise source in Germany is railway traffic. Probably, this type of source is not decisive for the noise reduction observed in our study, as restrictions were less limited. The regional railways of the main German railway provider decreased to 66% of the normal level and to 75% for the long-distance railways as of 22 April 2020 .As we also analyzed our data according to temporal differences, we found interesting results. For instance, considering weekdays and weekends, the highest noise reductions occurred on weekends, strictly speaking on Sundays. This result is in line with results from Asensio et al. (2020) , who fouAs with all research, this study has several strengths and limitations. The spatially high-resolution measurements using 22 recordings from different urban land use types proved to be a strength. Differently to many other studies of urban soundscapes, our approach also includes residential areas where people most frequently reside, giving us valuable information about associations between the built and acoustic environment. The high temporal resolution as well as the long-term measurements are further strengths of this research. The systematic approach to gathering data from a wide range of urban acoustic environments while taking into account possible seasonal variances deserves mention. Additionally, the implementation of a quality management procedure, including the application of a study protocol, qualification and training of the field staff, plausibility checks of assessed sound recordings, and calculated indices increases the plausibility of the results. One of the limitations is that currently we do not have small-scale meteorological data. Therefore, we could not account for meteorological conditions. Especially, wind gusts directly impact the recording microphone. Furthermore, wind can cause noise on building façades as well as modify sound propagation, which changes sound pressure levels accordingly ,33,34. WThe data collection for our automatic audio recordings started in May 2019, which is why a seasonal comparison between 2019 and 2020 is not possible. However, we do not believe that our data are mainly biased by seasonal effects for several reasons: in our data set, the seasonal differences between the time period February–April seem negligible, as for instance tree budding is still low or not yet pronounced. Furthermore, as already mentioned above, most studies to date investigating the impact of Sars-CoV-2 on noise levels have measured decreases in very similar ranges (3–5 dB), regardless of comparing the same seasonal periods between 2019 and 2020 or the weeks before and during lockdown measures. Overall, as this is an observational study, the aim is not to report causal relationships, but to describe noise levels during two very interesting periods, taking into account different land uses in an urban area.It is tempting to assume that the measured noise reductions are mainly due to the reduced traffic volume. Although it seems reasonable to expect that the nationwide reported decreases of traffic volume are of corresponding size in Bochum, it would be desirable to have more accurate, small-scale traffic data to evaluate the effects of individual and public traffic reductions on noise levels in more detail. Our 22 recording sites already cover a wide range of urban land use types. Still more recording sites are desirable to represent the most specific places of a city available to achieve a comprehensive understanding of the urban acoustic environment.The results presented may have implications for future urban public health measures and urban design. A reduction in traffic noise, as one main source of noise pollution , as well


The aim of the study is to develop artificial intelligence (AI) algorithm based on a deep learning model to predict mortality using abbreviate injury score (AIS). The performance of the conventional anatomic injury severity score (ISS) system in predicting in-hospital mortality is still limited. AIS data of 42,933 patients registered in the Korean trauma data bank from four Korean regional trauma centers were enrolled. After excluding patients who were younger than 19 years old and those who died within six hours from arrival, we included 37,762 patients, of which 36,493 (96.6%) survived and 1269 (3.4%) deceased. To enhance the AI model performance, we reduced the AIS codes to 46 input values by organizing them according to the organ location (Region-46). The total AIS and six categories of the anatomic region in the ISS system (Region-6) were used to compare the input features. The AI models were compared with the conventional ISS and new ISS (NISS) systems. We evaluated the performance pertaining to the 12 combinations of the features and models. The highest accuracy (85.05%) corresponded to Region-46 with DNN, followed by that of Region-6 with DNN (83.62%), AIS with DNN (81.27%), ISS-16 (80.50%), NISS-16 (79.18%), NISS-25 (77.09%), and ISS-25 (70.82%). The highest AUROC (0.9084) corresponded to Region-46 with DNN, followed by that of Region-6 with DNN (0.9013), AIS with DNN (0.8819), ISS (0.8709), and NISS (0.8681). The proposed deep learning scheme with feature combination exhibited high accuracy metrics such as the balanced accuracy and AUROC than the conventional ISS and NISS systems. We expect that our trial would be a cornerstone of more complex combination model. Since the 1970s, the injury severities have been classified through an anatomical-based coding system named the abbreviated injury scale (AIS). The AIS classifies individual injuries by body region from one to six. The system has been constantly revised and improved, and the latest revision (AIS 2005—Update 2008 and AIS 2015), including 1999 injury descriptors, was recently announced1.Traumatic injuries have long been scaled to assess the severity of patients and especially to predict mortality. To quantify the severity of such injuries, various metrics using anatomic and physiologic elements have been established based on conventional statistical tools such as logistic regression (LR)2. Similarly, the new ISS (NISS), which is designated to replace the ISS, pertains to the squares of the three highest AIS scores regardless of the body region5. Using the ISS and NISS, mortality has been predicted based on a certain score; however, the associated mortality prediction accuracy is low for patients with multiple injuries in different areas7.The most popular model to assess the trauma severity is the injury severity score (ISS), which pertains to the sum of the squares of the three highest AIS scores8. In addition, other combination models, such as A Severity Characterization of Trauma (ASCOT)9, the Harborview Assessment for Risk of Mortality (HARM)10, the Trauma Risk Adjustment Model (TRAM)11, and the Kampala Trauma Score (KTS)12 were developed. However, these scoring systems are overly complex to be applied in actual practice. Thus, the anatomic injury scoring systems based on ISS and NISS are still widely used despite their low prediction accuracy, and it is necessary to develop a simple and accurate prediction method.As a more complex combination model including the physiological status, the trauma and ISS (TRISS) has been widely used15. However, in the trauma field, an effective AI prediction model has not been established yet. Therefore, this study was aimed at developing an AI model to accurately predict mortality as an alternative to ISS and NISS.Recently, artificial intelligence (AI) technologies have been applied in various medical domains to predict the patients’ outcome with a high accuracy16. However, among the patients satisfying the above conditions, patients with only a superficial injury, first-degree burn and corrosive injury, frostbite, or intoxications are not registered in the KTDB. For this study, we considered the following inclusion criteria: (1) trauma patients registered in the KTDB, (2) adult patients aged over 19, (3) patients who stayed more than 6 h in the trauma center.This study was approved by the four institutional review boards of Wonkwang University Hospital (WKUH), Chonnam National University Hospital (CNUH), Wonju Severance Christian Hospital (WSCH), and Gachon University Gil Hospital (GUGH). Informed consent was waived. All methods were performed in accordance with the relevant guidelines and regulations. These four hospitals include the regional trauma centers of South Korea, corresponding to the level-1 trauma centers in the United States. In each regional trauma center, three or more dedicated trauma coordinators and surgeons review the medical records of the trauma patients to be input to the Korean trauma data bank (KTDB). To be registered in the KTDB as a trauma patient, the following eligibility criteria must be satisfied: (1) discharged with hopelessness, died in the trauma bay, or transferred to other hospitals, and (2) admitted in a trauma center17 registered in four trauma centers  are available. We excluded the data of patients aged less than 19 (n = 4562) or those who spent less than 6 h in the hospital (n = 648). The patient information, including age, gender and the AIS scores, is summarized in Table In the KTDB, the AIS 2005—Update 2008 data of 42,933 patientsThe data of 37,762 patients were considered and divided into the training and testing cohort in a 9:1 ratio in a stratified fashion according to the trauma center and survival status. As presented in Table The original AIS codes have 1999 injury codes, which are excessively complex to be used as input features in AI models and may lead to model overfitting. Consequently, we established new anatomical categories named Region-46 and Region-6 by reducing the AIS codes into 46 categories and six categories, respectively, based on the organ locations.To generate Region-46, we reduced the 1999 AIS codes to 46 features through organization according to the organ location, clinical significance, and frequency. The complete list of Region-46 is presented in Supplementary Table When using the Region-46 categories as input features, each input feature was the sum of the squares of the AIS scores for the same feature. For instance, if two AIS scores  corresponded to the neck among the Region-46, the AI model input for the neck feature was 2 + 42 + 22).Region-6 was considerably simpler than Region-46, as it scored the body regions identical to the six regions of the ISS . ISS takes the highest AIS severity code in each of the three most severely injured body regions. Each three AIS score is squared and added  DNN (Region-46) with 46 input features, (2) DNN (AIS) with the original 1999 AIS codes, and (3) DNN (Region-6) with six body regions.Furthermore, up to five hidden layers were examined, along with each layer depth (node) up to the previous layer depth (node). For the fully connected layers (FCs), the dropout rate was varied from 0 to 0.5 in 0.1 increments. The last FC layer was fed to a sigmoid layer, providing the probabilities for the patient mortality. We implemented and trained the models using TensorFlow and Keras. Moreover, model training was realized using the ADAM optimizer and a binary cross-entropy cost function with a learning rate of 0.0001 and batch size of 64 on an NVIDIA GeForce GTX 1080 Ti GPU.n = 33,986) were randomly shuffled for each trauma center and partitioned into 10 equal folds in a stratified manner: Each fold included 3284 survived and 114 deceased data. The process was repeated 10 times, with each of the 10 folds used once as the validation data. Because the amount of survived data overwhelmed the deceased data, we randomly downsampled the survived data. By matching the amount of data in the two groups, the model bias toward survived data could be minimized.For the hyperparameter search and cross-validation, a grid search with a 10-repeated tenfold cross-validation was performed. Among the 10 folds, a single fold was retained as the validation data, and the remaining nine folds were used as the training data. Specifically, the training data  is illustrated in Fig. By repeating this stratified tenfold cross-validation process 10 times, 100 models from the five-layer DNN were derived. Based on these models, we ensembled the results by averaging the final outputs associated with the mortality probabilities.n = 3776) and by applying the sensitivity, specificity, accuracy, and balanced accuracy metrics, defined asThe prediction performance of the DNN models was evaluated using the isolated testing dataset , and support vector machine (SVM). The models were separately trained to perform cross-validation and determine the optimal hyperparameters.ISS-16: mortality declared if ISS-25: mortality declared if NISS-16: mortality declared if NISS-25: mortality declared if Finally, we compared the results from the conventional ISS and NISS techniques, as follows:n = 12,280) was the highest, followed by upper extremity , face (n = 8310), head (n = 7200), rib (n = 6147) and thorax (n = 4763). Note that each patient may belong to multiple features due to multiple injuries.For all 37,762 patients, we counted the number of patients associated with each of the Region-46 features and summarized the counted numbers in Supplementary Table The results of the cross-validation accuracy with the metrics of sensitivity, specificity, accuracy and balanced accuracy are presented in Supplementary Table n = 3776) are summarized in Table The prediction performances of the DNN models evaluated using the independent testing dataset n = 776 are sThe prediction performances of the external AI models  and traditional prediction models  are presented in Table The highest balanced accuracy pertained to DNN (Region-46) (85.05%) and that of the other AI models ranged from 79.40 to 83.62%. Among the input features based on the DNN, the highest AUROC values pertained to Region-46 (0.9084), followed by those of Region-6 (0.9013), and AIS (0.8819); the corresponding values of ISS and NISS were 0.8709 and 0.8681, respectively  than AI models based on LR, RF, SVM, and DNN .We proposed a DNN model with 46 features, DNN (Region-46) as the AI prediction model to predict the in-hospital mortality of trauma patients, based on a comparison with DNN (AIS), DNN (Region-6), other AI models based on the LR, RF, and SVM methods, and traditional prediction models based on the ISS and NISS. In the independent testing datasets, DNN (Region-46) outperformed the ISS-16 as follows: sensitivity (83.46% vs. 80.32%), specificity (86.63% vs. 80.68%), accuracy (86.52% vs. 80.67%), balanced accuracy (85.05% vs. 80.50%), and AUROC (0.9084 vs. 0.8709).18. Most subsequent systems such as the NISS19, exponential ISS (EISS)20, and anatomic profile score (APS)21 could not supplant the ISS4. Nevertheless, the ISS system based on the AIS involves several limitations23. First, a major severe injury may be underestimated because only the single highest score is selected in the same region. Second, the severity may differ if a different combination of injuries has the same ISS. Third, the ISS and mortality do not have a linear association, and a negative relationship may also occur in certain ranges. Finally, the AIS has the same weighting for different organs even though all organs have a different prognosis.The AIS-based ISS has been widely used to evaluate the severity of trauma patients since its introduction in the 1970s24. The DNN model can assign different weights to each input data. Thus, we fragmented the conventional ISS system and used the AI methodology to overcome the problem of nonlinearity and weights for each AIS score. In this study, a key challenge was to decide the predictors and features, as the input variables significantly affect the results of machine learning20.These limitations of the ISS can be alleviated by using AI modelsn = 37,762) with highly comprehensive data involving a reasonable number of AIS score data points. The Ministry of Health and Welfare established up to 17 regional trauma centers in Korea (by 2021). All the regional trauma centers were mandated to register severe trauma patients in the KTBD. Numerous variables, including the demographics, pre-hospital and in-hospital information, time factors, clinical characteristics, vital signs, trauma scores, and final outcome information, were recorded. Therefore, the quantity and quality of the KTDB data were satisfactory25.A key advantage of DNN (Region-46) is that it was trained with a large training cohort  required only 59.52 s for training and 2.19 ms for instance testing, indicating its suitability for practical mortality prediction. Moreover, DNN (Region-6) provided accurate prediction results, requiring only 50.39 s for training and 2.11 ms for instance testing. Thus, if Region-46 is not promptly available, DNN (Region-6) can be used as an alternative method.The original AIS codes have 1999 injury codes, which are overly complex to be used as input features in AI models and may lead to model overfitting in the current training dataset involving 37,762 patients. The number of features considerably influences the performance of deep learning. The presence of excessively few or many features does not ensure high performance. In general, many data points are required for numerous features. Consequently, we established a new anatomical category, Region-46, by fragmenting the individual AIS codes and aggregating them into 46 anatomic regions. Our proposed Region-46 (46 input variables) could provide more accurate prediction results using more subdivided features than ISS (six input variables). In addition, it minimizes the overfitting issues using reasonably fewer features than AIS (1999 input variables). The better performance of the Region-46-based AI model was possible because 1999 AIS codes were with a sparse matrix, which contains very few non-zero values.Another advantage of Region-46 is that we derived it from the conventional AIS coding system. It indicates that the Region-46-based AI model enables us to train the model accurately within the existing coding system, without significant changes in the system such as the coding method. Nevertheless, the advantages of Region-46 are based on the assumption that there is no massive data. It is obvious that we can train AI models more accurately using more features from 1999 AIS codes if we have massive data. We postulate that a considerably larger dataset is required to utilize 1999 AIS codes as input features without overfitting. Thus, future research will proceed in the direction of increasing the number of features by collecting more data, and the ultimate goal is to use all 1999 AIS codes.8, ASCOT9, HARM10, TRAM11, and KTS12 use physiologic and demographic parameters to improve the performance. Although these complex combination models have not provided sufficient accuracy to replace the ISS, they have the potential to provide personalized prediction information of trauma severity. Thus, in our future work, we will extend our model to include the physiologic and demographic parameters towards personalized severity prediction. Finally, in this study, we considered mortality as an indicator of the severity of trauma patients as a conventional scoring system focused on mortality. However, regarding survivors, we also should be able to predict other outcomes such as morbidity, prevention effectiveness, or burden of cost. By developing new indicators that predict these outcomes, we could provide guidelines for entire trauma system including heath care provider, agencies, and institutions.In addition to the data sample size, this study involves several limitations to be solved. First, this study is retrospective, although the database was collected prospectively. In this study, we performed a retrospective study to investigate the potential of AI models based on our proposed new anatomical injury score. We believe that new prospective studies will be able to minimize the biases and establish the clinical impact of the prediction model. In addition, the prospective study should be able to update AI models in real-time in more regional trauma centers. For future work, we plan to develop a framework that can use real-time data in connection with all the regional trauma centers in Korea, which will improve the model for better generalization. Second, we excluded the patients who died within six hours from arrival because we assumed that the patients were likely not comprehensively evaluated owing to the insufficient time. This aspect may contribute to selection bias. Thus, our future work would include the patients irrespective of the time of death, which may provide a more robust AI model to predict the severity of trauma patients. Third, the input data did not include the physiologic and demographic parameters such as blood pressure, heart rate, mental status, respiration, age, sex, and comorbidities, while likely leading to an inherently limited accuracy. However, we noted the inherent potential of solely AIS code analysis that would be a basis of the future complex models. In particular, this study highlights the substantial scope for improvement in terms of the injury scale. Compared to ISS, more complex combination models such as TRISSIn conclusion, we developed a five-layer DNN model with an input layer involving 46 new trauma severity features (Region-46), which exhibited a higher prediction performance than the conventional ISS and NISS systems. To the best of our knowledge, this study represents the first attempt to employ AI prediction models using anatomic injury severity information. Furthermore, this study emphasizes the need for reinvention of a new injury severity scoring system. We expect that this research can provide reference to incorporate AI techniques in trauma care and improve our understanding of the determinants of injury severity. We believe our endeavor will contribute to reducing the societal burden of injury.Supplementary Information 1.Supplementary Information 2.


Central retinal vein occlusion (CRVO) is one of the most common retinal vascular diseases, which is closely related to systemic diseases like hypertension, diabetes and arteriosclerosis. Due of its blinding, it will seriously reduce the quality of life. Macular edema (ME) caused by CRVO is one of the serious complications of visual impairment. We found that the severity of ME in CRVO was positively associated with vascular endothelial growth factor (VEGF) in the anterior chamber. With the accelerated pace of modern life and the changed dietary structure, the incidence of this disease will continue to rise. Therefore, it is of great practical significance to seek effective treatment methods. Intraocular injection of anti-VEGF can effectively alleviate ME and improve visual acuity, showing excellent clinical application prospects. In recent years, there have been some new understandings and advances on the etiology and treatment methods of the present disease, such as the deepening into the molecular biology and gene level. Clinical studies on the efficacy of the disease have emerging. Therefore, a network meta-analysis (NMA) of anti-VEGF treatment for CRVO is particularly necessary to systematically compare its efficacy.The two reviewers will comprehensively retrieved electronic databases such as PubMed, The Cochrane Library, Wanfang database, Web of Science, Chinese Scientifific Journals Database, EMBASE, China National Knowledge Infrastructure, and China BioMedical Literature. A randomized controlled trial for CRVO against VEGF between January 2010 and June 2021 was included according to the relevant content of the study. In addition, 2 researchers will screen the literature to assess the risk bias for the included articles. We will evaluate the collected evidence and data using a Bayesian NMA method, and analyzed it with STATA and WinBUGS software.Anti-VEGF is one of the effective methods for ME in CRVO patients, accordingly, this study will evaluate its efficacy and safety using a Bayesian NMA system.This study can provide an effective rationale for the clinical application of anti-VEGF for CRVO, contribute to the treatment of CRVO and patient condition rehabilitation in clinical work.Do not require.INPLASY2021110073. The common vessel of retinal vein occlusion is CRVO. A study shows that there are about 2.5 million CRVO patients worldwide.At present, there are still many controversies on the classification, etiology, and treatment of CRVO, because of the severity of ME caused by CRVO. But some results have also been achieved. Studies on its etiology have shown that the severity of ME in CRVO is closely associated with vascular endothelial growth factor (VEGF) in the anterior chamber and positively with ME severity. Among these, VEGF levels were higher in the vitreous and anterior chambers than the nonischemic CRVO, ischemic CRVO. Expression of VEGF facilitates the clinical assessment of macular oedema severity in CRVO patients. Anti-VEGFs drugs are the primary means of treatment, which have a significant effect in solving ME and improving vision.Neovascularization is a common pathological change of many common eye diseases, and VEGF is an important promoter in the process of neovascularization. In recent years, intravitreal injection of anti-VEGF drugs has opened up a new direction for the treatment of neovascular eye diseases, and achieved good results. It has been verified in numerous systemic reviews and clinical trials that, anti-VEGF is the main method in the treatment of CRVO. However, its safety and effectiveness have not been compared. Network meta-analysis can take full advantage of clinical data and compare the efficacy of more than 3 treatments, with greater superiority over traditional meta-analyses. Therefore, we will use it to compare the safety and efficacy of anti-VEGF treatment of CRVO.22.1https://inplasy.com/inplasy-2021-11-0073/).We will follows the PRISMA-P guidelines, and register on the international platform of registered systematic review and meta-analysis protocols. The registration number is INPLASY2021110073 The best-corrected visual acuity changes at 1, 6, and 12 months, represented by ETDRS characters.(2)The central retinal thickness changes at 1, 6, and 12 months, represented by μm.(3)Best-corrected visual acuity improved or deteriorated by 15 or more ETDRS characters  at 6 months.(4)At 6 months, the cases of best corrected visual acuity was ≥20/40 or ≤20/200 Snellen.(5)The number of cases with ME in 6 months.(6)The number of cases with neovascular complications in 6 months.(7)The change of Nei VFQ-25 in 6 months.Safety data: the number of cases with intraocular or systemic adverse events, and counted by disease type.2.5The risk of literature bias was assessed using the Cochrane collaborative network quality evaluation tool, which is generated from the random number series, distributed and hidden, and whether the blind method is adopted or not. The results were divided into high-risk bias, low-risk bias, and unknown risk bias. After the evaluation, 2 researchers conducted the study Crosscheck.2.6P ≤ .05, the difference between the 2 groups was statistically significant. The analysis results are expressed in the form of a forest map.Revman 5.2.3 software was used for statistical analysis and processing of the data, and the entered data was checked repeatedly before the analysis to ensure accuracy. The effect model used in the analysis depends on the heterogeneity among the studies. When Measurement data or continuous value: The results were expressed as mean value ± mean difference and 95% confidence interval between the 2 groups.Count data or dichotomous data: it is expressed numerically, and the combined risk ratio is used as the effect scale. The analysis results, risk ratio and 95% confidence interval are expressed.2.72. Heterogeneity test ≥ 50%, P ≤ .1, indicating significant heterogeneity between studies. The random effect model was used when I ≤ 50%, P ≥ .01, indicating no significant heterogeneity, Fixed effect model was used for analysis.The heterogeneity among the studies was evaluated by I2.8We will consider the grouping analysis with sufficient data. Because some clinical trials do not provide complete standard deviation, the reliability of analysis results may be reduced by using the standard deviation of other clinical studies instead. Secondly, there are excellent clinical differences between ischemic and nonischemic CRVO in the course of disease and prognosis. Some clinical trials exclude or contain very few patients with ischemic CRVO, which may affect the overall analysis results. Therefore, the following 2 screening conditions were used for sensitivity analysis:(1)Clinical trials without standard deviation were excluded.(2)Clinical trials excluding patients with ischemic CRVO, <5% of patients with ischemic CRVO and an unknown proportion of patients with ischemic CRVO were excluded.2.9We will establish a coordinate system with the change of the best-corrected vision, central retinal thickness, the proportion of patients with vision change of 15 or more ETDRS characters, the proportion of patients with vision better than 20/40 Snellen or worse than 20/200 Snellen, the regression rate of ME, the proportion of patients with neovascular complications, and the change of NEI VFQ-25 score as indicators, and draw an inverted funnel diagram in it. Determine whether the raw materials have a publication bias according to whether the inverted funnel map is symmetrical.2.10The grading of recommendations assessment, development and evaluation framework[Evaluation parameters:(1)Best-corrected visual acuity.(2)Central retinal thickness.(3)Number of cases with best-corrected visual acuity not less than 15 ETDRS characters.(4)The number of cases with neovascular complications.(5)NEI VFQ-25.3CRVO is one of the most common retinopathy. Tortuous dilated retinal vein and retinal haemorrhage are the main ocular manifestations of retinal vein occlusion It's a record. Visual results are closely related to the ischemic state and integrity of capillaries around fovea. ME and neovascularization are the causes of severe visual loss, and the main complication of the loss of blood pressure. The pathogenesis is still unclear. However, the retinal vessels are anatomically narrowed, especially at the arteriovenous junction, at the cribriform plate The crowding effect of the layer, and many intravascular lesions that cause thrombosis Inflammatory diseases of trauma may lead to vascular occlusion.[Anti-VEGF drugs have been shown to improve visual and anatomical results significantly. After retinal vein occlusion, the expression level of VEGF increased significantly, and enhanced the exudation of the vascular wall. The possible mechanismCRVO is a common retinal vascular disease. ME caused by it is one of the serious complications of visual impairment. Intraocular injection of anti-VEGF can effectively alleviate ME and improve patients’ visual acuity, showing a great clinical application prospect. However, there is still a lack of sufficient evidence-based medical evidence in terms of safety and efficacy. Therefore, we will use network meta-analysis to compare the efficacy of anti-VEGF drugs for CRVO, so as to provide a credible theoretical basis for the clinical application of anti-VEGF drugs for CRVO.Conceptualization: Zhigao Liu.Data curation: Zhigao Liu, Shuya Wang.Formal analysis: Zhigao Liu, Aihua Ma, Bojun Zhao.Funding acquisition: Shuya Wang.Investigation: Zhigao Liu.Methodology: Zhigao Liu, Aihua Ma, Bojun Zhao.Project administration: Zhigao Liu.Resources: Zhigao Liu.Software: Zhigao Liu, Aihua Ma, Bojun Zhao.Supervision: Zhigao Liu.Validation: Zhigao Liu.Visualization: Zhigao Liu.Writing – original draft: Zhigao Liu, Shuya Wang.Writing – review & editing: Zhigao Liu, Shuya Wang.