In this study, we built clinical- and radiomics-based models to predict lesions/patients at low risk based on a combined clinical-genomic classification system. Eighty-three multi-parametric MRI exams from 78 men were analyzed. Several models for lesion classification were built using a minimal clinical variables subset and radiomic features from the lesion and normal tissues. The models were also evaluated for patient classification. In all cases, the radiomic features improved the performance. To the best of our knowledge, this is the first study to demonstrate that machine learning radiomics-based models can predict patients’ risk using combined clinical-genomic classification.The utilization of multi-parametric MRI (mpMRI) in clinical decisions regarding prostate cancer patients’ management has recently increased. After biopsy, clinicians can assess risk using National Comprehensive Cancer Network (NCCN) risk stratification schema and commercially available genomic classifiers, such as Decipher. We built radiomics-based models to predict lesions/patients at low risk prior to biopsy based on an established three-tier clinical-genomic classification system. Radiomic features were extracted from regions of positive biopsies and Normally Appearing Tissues (NAT) on T2-weighted and Diffusion-weighted Imaging. Using only clinical information available prior to biopsy, five models for predicting low-risk lesions/patients were evaluated, based on: 1: Clinical variables; 2: Lesion-based radiomic features; 3: Lesion and NAT radiomics; 4: Clinical and lesion-based radiomics; and 5: Clinical, lesion and NAT radiomic features. Eighty-three mpMRI exams from 78 men were analyzed. Models 1 and 2 performed similarly , but radiomics significantly improved the lesion-based performance of the model in a subset analysis of patients with a negative Digital Rectal Exam (DRE). Adding normal tissue radiomics significantly improved the performance in all cases. Similar patterns were observed on patient-level models. To the best of our knowledge, this is the first study to demonstrate that machine learning radiomics-based models can predict patients’ risk using combined clinical-genomic classification. Prostate cancer is the most common cancer in American men. In 2022, more than a quarter of a million men was diagnosed with the disease . ClinicaProstate needle biopsy carried out under multi-parametric MRI (mpMRI) guidance has gained acceptance as a key component of patient management. From the biopsy tissue, both histopathological and genomic biomarkers are used in clinical management. After prostate biopsy, clinicians have various tools for risk assessment, including the National Comprehensive Cancer Network (NCCN)  risk strActive surveillance (AS) has emerged as a safe alternative to immediate treatment in low-risk patients ,9,10. ASThe use of mpMRI for the detection and classification of prostate cancer is rapidly evolving due to its growing availability and the efforts in the radiology community to standardize the reporting of suspicious prostate lesions (Prostate Imaging Reporting and Data System (PI-RADS)   trial “MRI-Guided Biopsy Selection of Prostate Cancer Patients for Active Surveillance versus Treatment: The Miami MAST Trial“ and a phase II randomized clinical trial “MRI-Guided Prostate Boosts Via Initial Lattice Stereotactic vs. Daily Moderately Hypofractionated Radiotherapy (BLaStM)” . Both trials were approved by the Institutional Review Board at the University of Miami and all patients signed appropriate informed consent for treatment and the analysis of MRI and biopsy tissue for research purposes. Patients in both trials underwent mpMRI followed by MRI-ultrasound (MRI-US) fusion biopsies. Patients also agreed to have their tissue sent to Veracyte Inc. , and their data are included in this research. During the initial phase of the trials between 2014 and 2017, all cancer-positive biopsy cores with larger than 1 mm of cancer were sent to Veracyte for gene expression analysis. In addition, if available, positive cores from the patient’s diagnostic biopsy  were also sent.MRI sequences and sequence parameters were consistent with the recommendations for PI-RADSv2 . The exaThe image segmentation and the co-registration of the biopsy/gene expression and radiomics of the lesion are illustrated in MRI-US biopsies were carried out in UroNav . Tissue from the identified targets was obtained for pathology and gene expression analysis. For patients in BLaStM, only suspicious areas seen on mpMRI were sampled. For patients in MAST, standard template biopsies were also collected.The biopsy needle track coordinates (beginning and end) were recorded and transferred in MIM 7.2.3 . The tumor Regions of Interest (ROIs) were assigned as the volumes of HRS = 6 coinciding with the individual needle tracks . In caseFor normalization of the T2-weighted MRI intensities, a multireference normalization approach was utilized . Using tRadiomic features were extracted as described in Kwon et al.  using a In summary, 162 quantitative imaging variables  were anaTissue microdissection, RNA extraction, and amplification and microarray hybridization were performed in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory facility, as described previously in . AmplifiThe Spratt clinical-genomic risk score is calculated by assigning a numeric value of 0, 1, 2 and 3 to the low, favorable intermediate, unfavorable intermediate, and high/very high NCCN risk groups, respectively , and a nTo evaluate the contribution of radiomic variables to the predictive value of the clinical variables, we evaluated five models for predicting low-risk lesions/patients as defined by Spratt’s criteria . In FiguModel 1: A clinical model using patient’s age, PSA density (PSAD), digital rectal exam (DRE), and PI-RADS for input. Importantly, this model did not incorporate the results of biopsy tissue, as we wanted to simulate a pre-biopsy clinical scenario and limited the variables to the initial prostate exam.Model 2: Lesion-based radiomics model.Model 3: Lesion and NAPZ/NATZ radiomics model.Model 4: A combined clinical and lesion radiomics model.Model 5: A combined clinical and lesion/NAPZ/NATZ radiomics model.For Model 1, all pre-biopsy clinical variables were used. For the radiomics models, since imaging data are highly correlated and multi-dimensional, we used a penalized logistic regression model (GLMNET) to select important imaging variables that predict low-risk lesions . Radiomiwww.R-project.org (accessed on 1 May 2023)).The area under the receiver operating characteristic (ROC) curve (AUC) is reported as a performance measure for each trained model. AUC comparison is performed using the Venkatraman and Begg method . For eacA total of 231 biopsy cores from 78 men were analyzed for this study, with 46 men coming from the MAST active surveillance trial and 32 from the BlaStM primary radiation trial. . As the A total of 83 mpMRI exams were analyzed. When available, both the diagnostic and protocol biopsies were matched with their corresponding mpMRIs. Thus, for five patients two mpMRI exams were analyzed. A detailed breakdown by MRI instruments is given in In ROC curves and AUCs for the five trained models in all patients and subset analysis for patients with negative DRE (DRE = 0) are shown in Due to the high performance of the intensity’s features, we tested the value of using only first-order radiomics by re-creating models Model 1–5. There is a major advantage of using only intensities, assuming that the resultant model is not substantially underperforming relative to the full variable selection. Intensity futures are easy to compute, and they are highly reproducible between groups and software. The results from the intensities-only analysis are given in the Image-based automated prostate cancer classification is an area of active investigation. The standard underlying schema of the approach consists of feature extraction and classification. In the majority of radiomic applications, the goal is to predict the Gleason Score/Group Grade . Here, The main finding of our study is that it is feasible to build radiomics-based models that can predict the patient risk based on a clinical-genomic classifier. The performance of the lesion radiomics model  did not outperform the clinical Model 1, AUC = 0.8353. We hypothesized that the DRE results are driving the high performance of the clinical factors because of the strong association with abnormal DRE in high-risk patients. In a subsequent subset analysis, only of patients with negative findings on DRE (DRE = 0), Model 2’s AUC = 0.832 was markedly, albeit not significantly, higher than Model 1’s AUC = 0.763. In both cases, the AUCs of the lesion radiomic variables were almost the same, indicating the robustness of the model, while the exclusion of the DRE deteriorated the performance of the clinical variables. The combined models based on radiomics and clinical characteristics in all comparisons improved the predictive performance. Interestingly, radiomic features of the lesion environment, NAPZ and NATZ, contributed significantly to the overall model performance. In particular, the AUC of Model 1  increased modestly, albeit significantly, from 0.835 to 0.871 in Model 4 . However, when the radiomics of PZ/TZ was added (Model 5), the AUC markedly increased to 0.962. The same pattern was observed in the subset analysis of patients with DRE = 0. Clinical decisions, on the other hand, are made on a per-patient basis rather than per-lesion. The outlined trends in model improvement after combining radiomic and clinical variables in Model 5 is also evident in per-patient models  and radiomics, and the reported results discriminated between (i) malignant vs. benign prostate lesion (AUC = 0.889) and (ii) clinically significant prostate cancer (csPCa) vs. clinically insignificant prostate cancer (cisPCa) (AUC = 0.844)    [®)  [The associations between prostate mpMRI features and gene expression have been investigated before . We demoUT, USA)  and GenoCA, USA) . The preCA, USA)  and HectCA, USA) . Both stSimilar to our previous work , we analAnother unique aspect of our approach is the inclusion of NAPZ and NATZ in the radiomics pipeline. This was motivated by our previous gene ontology analysis that identified specific radiomic features, including from the tumor micro-environment, associated with immune/inflammatory response, metabolism, cell, and biological adhesion . Indeed,Despite the large heterogeneity in terms of magnets and manufacturers, about one-third of the variables on both lists are related to image intensities  systems are hindered by an absence of standardization for DCE-MRI analysis. The Quantitative Imaging Network (QIN) at the National Cancer Institute (NCI) conducted two challenges among premier academic medical centers, and the evaluated pharmaco-kinetic parameters Kvariable ,42. Howevariable . In addivariable . In Montvariable , radiomiOur study has several limitations, including the relatively small sample size, precluding analysis of a separate validation set. Evaluation in a larger prospective cohort would be beneficial to validate these preliminary findings. This study was conducted within a single-institution academic setting with subspecialized multidisciplinary expertise and the performance of the created models may not be generalizable to community practice. In the analysis, we included only first- and second-order radiomic features to avoid overfitting.In conclusion, our study demonstrated that a machine-learning radiomics-based model is capable of predicting novel clinical-genomic classifications. While there are several reports on the association of radiomic variables with GS/GG, to the best of our knowledge, this is the first report for predicting an integrated clinical-genomic classification.


Pathogenic copy-number variants (CNVs) can cause a heterogeneous spectrum of rare and severe disorders. However, most CNVs are benign and are part of natural variation in human genomes. CNV pathogenicity classification, genotype–phenotype analyses, and therapeutic target identification are challenging and time-consuming tasks that require the integration and analysis of information from multiple scattered sources by experts.Here, we introduce the CNV-ClinViewer, an open-source web application for clinical evaluation and visual exploration of CNVs. The application enables real-time interactive exploration of large CNV datasets in a user-friendly designed interface and facilitates semi-automated clinical CNV interpretation following the ACMG guidelines by integrating the ClassifCNV tool. In combination with clinical judgment, the application enables clinicians and researchers to formulate novel hypotheses and guide their decision-making process. Subsequently, the CNV-ClinViewer enhances for clinical investigators’ patient care and for basic scientists’ translational genomic research.https://cnv-ClinViewer.broadinstitute.org and the open-source code can be found at https://github.com/LalResearchGroup/CNV-clinviewer.The web application is freely available at  One of the reasons for genetic disorders is copy-number changes of one or more genes, resulting from deletions, duplications, or other genomic rearrangements. Most disease-associated CNVs are unique, cause severe complex disorders, and are often hard to distinguish from benign CNVs frequently found in the general population .Although the average size of pathogenic/likely pathogenic CNVs in ClinVar  of 9.7 MSeveral bioinformatics tools, often fully-automated, have been developed for clinicians and researchers to facilitate large-scale CNV classification according to the ACMG guidelines  . These ghttps://shiny.rstudio.com/) which transforms regular R code into an interactive environment that can follow and “react” to remote-user instructions. The pre-processed data alongside the R/Shiny code was uploaded as a stand-alone Ubuntu image with Google Cloud services. The image was deployed into a Google Virtual Machine (VM) using the googleComputeEngineR package . The CNV-ClinViewer web server (https://cnv-ClinViewer.broadinstitute.org/) is compatible with all commonly used Internet browsers.The CNV-ClinViewer was developed with the Shiny framework of R studio software , and the interactive visualizations and tables are rendered using the ggplot2 , plotly (v.4.9.4.1 https://plotly-r.com), and DT  R packages. For the gene set enrichment analysis, the enrichr R package  that provides an interface to the Enrichr database is used.For the classification of uploaded CNVs, the clinical interpretation tool ClassifyCNV  includinhttps://github.com/LalResearchGroup/CNV-clinviewer).The CNV-ClinViewer is an open-source project, and its code will continue to grow and improve through version control in the GitHub repository  or GRCh38/hg38 (https://www.ncbi.nlm.nih.gov/data-hub/genome/GCF_000001405.40/), either by copy-pasting or by uploading a tab-separated text or Excel file (max. number of CNVs = 10 000). Minimal required information for each CNV, including whole chromosome trisomies and monosomies, is the chromosome, start, end, and CNV type (deletion or duplication). Optionally, the user can provide sample IDs, phenotype information for filtering and a score of manually assessed evidence categories of the 2019 ACMG standard guidelines (see below). Details and example files can be found in the help section and on the about page of the CNV-ClinViewer.The CNV-ClinViewer allows simultaneous analysis of single or multiple CNVs, irrespective of the technology used to identify them. It requires as input the genomic coordinates of CNVs based on the human reference genome GRCh37/hg19 , and gene dosage sensitivity scores  terms , and knon = 14)  from patients with complex developmental disorders from the literature (n = 14) . Here, tn = 14) . Next, tent CNVs . In addient CNVs  and retrent CNVs  as well ent CNVs . OverallBy aggregating more than 250 000 population and patient CNVs, annotating various gene scores and clinical annotations, and integrating useful existing bioinformatics tools, we developed a novel and user-friendly interface as a decision support tool for the clinical evaluation of CNVs and comparative visual inspection.CNV analysis and interpretation tools and, in general, clinical decision support tools can make patient care more efficient, cost-effective, and guideline concordant. However, although the prediction results from many approaches are promising, their value is limited by their lack of interpretability and human intuition. The black-box nature of some pathogenicity predictions can further exacerbate trust issues and worsen the overall experience . To addrTo ensure that a tool is easy to use and is designed for target users at each development stage, human-centered design methods and principles should be applied . Such meOn the one hand, the CNV-ClinViewer will assist clinicians, clinical geneticists, and genetic counselors in analyzing and interpreting CNV data and improving objectivity and accuracy in the clinical work-up. On the other hand, the collected and integrated knowledge combined with clinical judgment will enable clinicians and researchers to formulate novel hypotheses and guide their decision-making process.https://www.cnv-ClinViewer.broadinstitute.org/), including complete documentation on the use of the website.The current features of the tool are focused on large CNVs that intersect several genes when gene prioritization plays a role in the analysis. Future versions will increase the granularity of the tool, e.g. by providing a more detailed gene track that includes exons and introns, and different transcripts with expression data. With that, it will bring more value for interpreting intragenic deletions and duplications. Also, to integrate with existing workflows, we plan to develop an application programming interface (API) to query the system and fetch the results without using a graphical user interface. Overall, the CNV-ClinViewer is the first framework that enables interactive exploration of CNV data and semi-automated variant classification. With its scalable architecture, the web application is well suited for both genome-wide (re-)evaluations of large datasets and the small number of CNVs. The CNV-ClinViewer is an open-source tool (btad290_Supplementary_DataClick here for additional data file.


The disadvantages and complications of computed tomography (CT) can be minimized if CT is performed in rib fracture patients with high probability of intra-thoracic and intra-abdominal injuries and CT is omitted in rib fracture patients with low probability of intra-thoracic and intra-abdominal injuries. This study aimed to evaluate the factors that can identify patients with rib fractures with intra-thoracic and intra-abdominal injuries in the emergency department among patients with rib fracture.This retrospective observational study included adult patients (age ≥ 18 years) diagnosed with rib fracture on chest radiography prior to chest CT due to blunt chest trauma in the emergency department who underwent chest CT from January 2016 to February 2021. The primary outcomes were intra-thoracic and intra-abdominal injuries that could be identified on a chest CT. Multivariate logistic regression analysis was performed.p < 0.001), bilateral rib fractures were frequent , and lateral and posterior rib fracture was more frequent , and displacement was more frequent  in the group with intra-thoracic and intra-abdominal injuries than in the group with no injury. The number of rib fractures , lateral rib fracture , and posterior rib fracture  were independently associated with intra-thoracic and intra-abdominal injuries. The optimal cut-off for the number of rib fractures on the outcome was three. The number of rib fractures ≥ 3  was independently associated with intra-thoracic and intra-abdominal injuries.Among the characteristics of rib fractures, the number of rib fractures was greater (5.0 [3.0–7.0] vs. 2.0 [1.0–3.0], 2 supplementation require chest CT to identify significant intra-thoracic and intra-abdominal injuries in the emergency department.In patients with rib fractures due to blunt trauma, those with lateral or posterior rib fractures, those with ≥ 3 rib fractures, and those requiring O Rib fractures occur frequently in patients experiencing blunt chest traumas. In the United States, approximately 250,000 patients visit the emergency department annually due to rib fractures. Moreover, the number of patients visiting the emergency department is increasing in the United States , 2. CompChest radiography, ultrasonography, and computed tomography (CT) can be performed in patients with rib fractures in the emergency department –5. HowevCT is the modality of choice for evaluating rib fractures and associated organ injuries in the emergency department –5. HowevThe disadvantages and complications of computed tomography (CT) can be minimized if CT is performed in rib fracture patients with high probability of intra-thoracic and intra-abdominal injuries and CT is omitted in rib fracture patients with low probability of intra-thoracic and intra-abdominal injuries. Therefore, this study aimed to evaluate the factors that can identify patients with rib fractures with intra-thoracic and intra-abdominal injuries in the emergency department among patients with rib fracture.This retrospective observational study was conducted at Korea University Ansan Hospital, the only tertiary academic teaching hospital in Ansan-si, Korea . ApproxiThis study was approved by the Institutional Review Board of Korea University (2022AS0117). The institutional review board waived the requirement of informed consent due to the retrospective observational design of the study.In this study, diagnosis of rib fracture was based on chest radiography. Intra-thoracic and intra-abdominal injuries that could be identified on chest CT were obtained. The location of intra-thoracic injury was classified as mediastinum, aorta, diaphragm, lung, pericardium, heart, or thoracic vertebra. The locations of intra-abdominal injuries were classified as liver, spleen, kidney, adrenal gland, pancreas, gut, abdominal vessels, and lumbar vertebra.Intra-thoracic and intra-abdominal injuries were defined as injuries with an Abbreviated Injury Scale score ≥ 2 in the intra-thoracic and intra-abdominal organs. Significant intra-thoracic and intra-abdominal injuries were defined as intra-thoracic and intra-abdominal injuries except for occult pneumothorax, scanty hemothorax, and small lung contusions that can be only identified on a chest CT (not visible on chest radiography). Occult pneumothorax, scanty hemothorax, small lung contusions, and no injuries were considered nonsignificant intra-thoracic and intra-abdominal injuries.The mechanism of injury was dichotomized into high-energy and low-energy trauma. High-energy trauma comprised motor vehicle accidents, pedestrian trauma (hit by a motor vehicle), falls of more than 3 m, and industrial trauma. Low-energy trauma include falls within a height level, simple contusions, assault, and unknown trauma mechanisms.Characteristics of rib fractures include the location , displacement of more than 50% of the ribs, bilateral rib fractures, and lower rib fractures. A lower rib fracture was defined as a fracture between the 8th and 12th ribs.Adult patients (age ≥ 18 years) diagnosed with rib fracture on chest radiography prior to chest CT due to blunt chest trauma in the emergency department and who underwent chest CT between January 2016 and February 2021 were included in the study. Patients who had a penetrating chest trauma, were age < 18 years, or did not undergo chest CT were excluded. Patients with rib fractures due to cardiopulmonary resuscitation were excluded.The following data of the patients were extracted from electronic medical records: sex, age, comorbidities, trauma mechanism, administration of antiplatelet or anticoagulant drugs, and initial vital signs upon arrival at the emergency department. Data on management in the emergency department, such as oxygen supplementation, use of mechanical ventilators, and transfusion, were collected. Additionally, the results of chest radiography, chest CT, and injuries to the head, neck, face, extremities, and external wounds were collected. The injury severity score was calculated.The primary outcomes were any intra-thoracic and intra-abdominal injuries that could be identified on a chest CT. The secondary outcomes were significant intra-thoracic and intra-abdominal injuries.Continuous variables are expressed as medians and interquartile ranges or means and standard deviations, according to the distribution of variables. Continuous variables were compared using the Mann − Whitney test or Student’s t-test, as appropriate. Categorical variables are expressed as numbers and percentages and were compared using the chi-square test or Fisher’s exact test.Multivariable logistic regression analyses were performed to identify independent factors associated with the outcomes. Factors that were significant at the level of 0.1 in univariable logistic regression analyses and those that were well-known risk factors in previous studies were included in the multivariable logistic regression model. Further analyses were performed to identify independent factors associated with intra-thoracic injuries. The Hosmer − Lemeshow test was performed to evaluate the goodness of fit of the models.Receiver operating characteristic (ROC) curves of the number of rib fractures and outcomes were performed. The area under the curve, sensitivity, and specificity were determined. The Youden index was used to determine the optimal cut-off point. Additional analyses were performed using categorical values according to the optimal cut-off point.Subgroup analysis was performed among patients without injuries to the head, neck, face, extremities, and external wounds (patients with trauma to the chest and upper abdomen only).p-value less than 0.05 was considered significant in all statistical analyses. Statistical analyses were performed with R version 4.0.2 software .A From January 2016 to February 2021, 499 patients were diagnosed in the emergency department with rib fractures on chest radiography prior to chest CT due to blunt chest trauma. Three patients were excluded because they were aged < 18 years, and 91 patients were excluded because chest CT was not performed. Four patients were further excluded as their rib fractures were due to cardiopulmonary resuscitation. Thus, a total of 401 patients were included in this study . Among the characteristics of rib fractures, the number of rib fractures was higher , bilateral rib fracture was more frequent , lateral and posterior rib fracture was more frequent , and displacement was more frequent  in the group with intra-thoracic and intra-abdominal injuries than in the group with no injury. Traumatic brain injury, facial bone fractures, and fractures in the extremities were more common in the group with intra-thoracic and intra-abdominal injuries than in the group with no injury . Meanwhile, comorbidities, medications, and initial vital signs were not significantly different between the groups.Table 2 supplementation, mechanical ventilation, and transfusion than the group without significant injury . Among the characteristics of rib fractures, the number of rib fractures was greater  and bilateral rib fractures were frequent  in the group with significant intra-thoracic and intra-abdominal injuries than in the group with no significant injury. Anterior, lateral, and posterior rib fractures were more frequent  in the group with significant intra-thoracic and intra-abdominal injuries than in the group with no significant injury. Moreover, displacement was more frequent  in the group with significant intra-thoracic and intra-abdominal injuries than in the group with no significant injury. Traumatic brain injury and fractures in the extremities were more frequent in the group with significant intra-thoracic and intra-abdominal injuries than in the group without significant injury . Meanwhile, comorbidities, medications, and initial vital signs, except heart rate, were not significantly different between the groups.Table 2 supplementation, number of rib fractures , lateral rib fracture , and posterior rib fracture  were independently associated with any intra-thoracic and intra-abdominal injuries. The trauma mechanism, initial vital signs, and injuries at other sites were not independently associated with any intra-thoracic and intra-abdominal injuries , posterior rib fracture , pelvic bone fracture, and extremity fracture were independently associated with significant intra-thoracic and intra-abdominal injuries. The trauma mechanism and initial vital signs were not independently associated with significant intra-thoracic and intra-abdominal injuries (Table p > 0.05).Requirement of Op < 0.001). The optimal cut-off point was 3, with a sensitivity of 62.7% and specificity of 82.0% . The optimal cut-off point was three, with a sensitivity of 71.4% and a specificity of 69.4%  , lateral rib fracture , and posterior rib fracture  were independently associated with any intra-thoracic and intra-abdominal injuries. The number of rib fractures ≥ 3  and posterior rib fracture  were independently associated with significant intra-thoracic and intra-abdominal injuries.In multivariable logistic regression analysis, the number of rib fractures ≥ 3 , lateral rib fracture , and posterior rib fracture  were independently associated with any intra-thoracic injuries.In multivariable logistic regression analysis, age, requirement of O2 supplementation, number of rib fractures , and posterior rib fracture  were independently associated with significant intra-thoracic injuries.Requirement of Op = 0.048), and posterior rib fracture  were independently associated with intra-abdominal injuries.In multivariable logistic regression analysis, age, requirement of transfusion, lower rib fracture , and posterior rib fractures  were independently associated with any intra-thoracic and intra-abdominal injuries. Requirement of O2 supplementation, requirement of transfusion, number of rib fractures , and posterior rib fracture  were independently associated with significant intra-thoracic and intra-abdominal injuries , lateral rib fracture , and posterior rib fracture  were independently associated with any intra-thoracic and intra-abdominal injuries. Requirement of O2 supplementation, mechanical ventilator use, requirement of transfusion, number of rib fractures , posterior rib fracture , and extremity fracture were independently associated with significant intra-thoracic and intra-abdominal injuries. We attempted to include patients similar to those observed in real-world conditions and performed an analysis using variables that can be easily, rapidly, and noninvasively obtained from routine clinical practice. The results of our study may help physicians in early decision-making to perform chest CT in patients with rib fractures in the emergency department.This study had several limitations. First, due to the retrospective observational study design, covariables might have been missed. Second, this study was conducted at a single center. The characteristics of patients with rib fractures may differ between hospitals or trauma centers. Further multicenter or multi-trauma center studies are warranted. Third, this study evaluated the outcomes of the initial chest CT. Delayed organ injury due to blunt trauma may have occurred later. However, we believe that the proportion of delayed significant organ injuries is minimal. In addition, since this study was conducted at only a tertiary academic teaching hospital in one region, patients with delayed significant organ injuries might have revisited our hospital, but we did not observe any such cases in this study. Fourth, laboratory data were not included in the analysis. A previous study reported that the results of arterial blood gas analysis, such as pH and base excess, may be helpful factor . In the 2 supplementation are factors that indicate the need for chest CT to identify intra-thoracic and intra-abdominal injuries in the emergency department. The results of our study may help physicians in early decision-making to perform chest CT in patients with rib fractures in the emergency department.Among blunt trauma-induced rib fracture characteristics, posterior rib fractures, lateral rib fractures, ≥ 3 rib fractures or number of rib fractures, requirement of O


Web-implemented exercise intervention is the latest and innovative method to improve people's mental health. Currently, many studies have proven that web-implemented interventions are effective to improve depression and anxiety in adults. However, the influence of different web-implemented exercise interventions on depression and anxiety in patients with neurological disorders is still unclear.The study aims to systematically summarize the type and content of web-implemented exercise interventions and quantify the effect of different web-implemented exercise interventions on depression and anxiety in patients with neurological disorders.Four literature databases  were searched. The literature search considered studies published in English or Chinese before October 13, 2022. Randomized controlled trials (RCTs) that participants accepted web-implemented interventions were included. Two authors independently extracted data and assessed the risk of bias for included studies. Standardized mean differences (SMD) with 95% CI were used to integrate the effect size.I2 = 75%; P < 0.00001) and anxiety  in patients with a neurological disorder. The subgroup analysis showed that the effectiveness of the web-implemented exercise intervention was influenced by several factors, such as web-implemented exercise intervention type, component, and intervention duration.16 RCTs  were included. The results showed that web-implemented exercise intervention had a significant effect on depression (SMD = −0.80; 95% CI, −1.09 to −0.52; Web-implemented exercise intervention has a relieving effect on depression and anxiety symptoms in patients with neurological disorders. Additionally, the intervention type, intervention duration, and component can influence the effect size.https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier: CRD42023409538. The Global Burden of Disease (GBD) shows that the impact of neurological disease on global health is grossly underestimated and the prevalence of neurological and is also on the rise . Over thMental disorders are likely to be the leading cause of disease burden worldwide by 2030 . To someAs a non-medicine and non-invasive intervention, exercise has been proven effective in relieving depression and anxiety –18. CompIn recent years, with the development of electronic technology and the lockdowns caused by COVID-19, more and more people prefer “online exercise.” The web-implemented exercise interventions which support people who do not seek help from health services because of social stigma or transport problems could prescribe a structured exercise program to be carried out at home with varying degrees of supervision, differing from interventions that focus solely on motivating people to exercise , 22. UsiWeb-implemented exercise can also play an essential role in the improvement of mental health in patients. Turner et al. have evaluated the effect of the web-implemented exercise intervention on the mental health of MS patients. They have provided the 6-month personalized exercise guidance using a remote health system to monitor exercise plans and progress for MS patients in the experimental group and a 6-month self-directed education method for MS patients in the control group. Eventually, they found that 53.3% of MS patients in the experimental group experienced a clinical improvement in depression symptoms, whereas only 9.1% of MS patients in the control group experienced a clinical improvement in depression symptoms . ObviousTherefore, the purpose of this study was to summarize various types of web-implemented exercise and integrate the effects of different web-implemented exercise interventions on depression and anxiety in patients with different neurological disorders. It has important value for the development of exercise interventions on mental health, especially for the future expansion of VR exergames and intelligent exercise intervention modes.http://www.crd.york.ac.uk/PROSPERO), registration number: CRD42023409538. We searched two English databases, including PubMed and Web of Science (WOS), and two Chinese databases, including CNKI and WANFANG Data. All articles were published before October 13, 2022. This search followed the Preferred Reported Items for Systematic Review and Meta-analysis (PRISMA) guidelines. The protocol was registered on the international prospective register of systematic reviews  participants were diagnosed with neurological diseases; (2) the experimental group used tele-exercise intervention or game-based exercise intervention, all exercise interventions should be based on the Internet; (3) the interventions in control group include empty, usual care, general physical therapy or exercise without web-implemented methods (offline); (4) the outcomes were the common indicators reflecting depression and anxiety, such as the scores of HADS, BDI, BAI, etc. (5) only randomized controlled trials (RCTs) were selected.Studies were excluded if they met any of the following exclusion criteria: (1) the articles were not published in English or Chinese; (2) no full-text or data was available; (3) gray literature such as conference abstracts, literature review, thesis or dissertation; (4) no web-implemented exercise intervention involved in the experimental group; (5) using web-implemented exercise interventions in the control group; (6) the intervention in the experimental group was cognitive behavior therapy or mindfulness-based intervention only.After searching the articles based on the search strategy, all studies were exported into the reference management software EndNote 20 by one researcher (HY.Z). Two researchers (R.W and M.C) independently screened the articles. After removing the duplicates and reviewing the title and abstract, the articles those are completely incompatible with the topic were deleted. Finally, two researchers (R.W and M.C) confirmed the final included studies according to the inclusion and exclusion criteria. If these two authors had an agreement and the argument was not achieved, a third arbitrator (HY.Z) would make the final determination.Two researchers (R.W and M.C) independently extracted data from the included studies. The following information was extracted into standardized data tables: (1) study details ; (2) participants ; (3) components of interventions ; (4) outcomes (the measurements of depression and anxiety).Two researchers (M.C and R.W) used the Cochrane risk of bias collaboration tool to examine the study quality independently. The bias includes: (1) random sequence generation (selection bias); (2) allocation concealment (selection bias); (3) blinding of participants and personnel (performance bias); (4) blinding of outcome assessment (detection bias); (5) incomplete outcome data (attrition bias); (6) selective reporting (reporting bias); and (7) other bias. Three levels were used to evaluate the quality of included articles . If the results did not match, a third researcher would make the final decision (HY.Z).We used Review Manager software (Review Manager 5.4) to conduct the meta-analysis. In this study, depression and anxiety were assessed using different scales. To be specific, the depression was assessed by the Hamilton depression scale (HAMD), Geriatric depression scale (GDS), Beck depression inventory (BDI), Self-rating depression scale (SDS), Depressive symptoms-9 subscale (PHQ-9), Hospital anxiety and depression (HADS) and EuroQoL (EQ-5D). The anxiety was assessed by the Hamilton anxiety scale (HAMA), beck anxiety inventory (BAI), and Self-rating anxiety scale (SAS).post−intervention ± SDpost−intervention) of the outcome and changes from baseline (Meanchanges ± SDchanges) could be applied to synthesize the effect size  to integrate the total effect size. According to the Cochrane Handbook, both the post-intervention values , cognitive impairment , stroke , and Parkinson's disease .Web-implemented exercise interventions were separated into two main categories , respectively . There are six studies (37.5%) involving tele-exercise intervention and 10 studies (62.5%) involving VR exergame . In addition, according to the concrete contents of interventions in the experimental group, 10 studies (62.5%) conducted single-component interventions (only web-implemented exercise) and six studies (37.5%) conducted multi-component interventions . In terms of outcomes, 15 studies (93.8%) involved depression and seven studies (43.8%) involved anxiety.I2 = 75%, p < 0.00001).Seventeen data points from 15 studies reported the influence of web-implemented exercise interventions on depression in patients with neurological symptoms. I2 = 75%, p = 0.0003).Eight data points from seven studies reported the influence of web-implemented exercise interventions on anxiety in patients with neurological symptoms. I2 = 77%, P < 0.0001) and VR exergame  had a significant relieving effect on depression. According to the effect size, the tele-exercise interventions appeared to have a better-alleviating effect on depression than VR exergame interventions. For contents of tele-exercise intervention, both face-to-face intervention  and offline delayed interventions  had a significant effect on reducing depression. For the components of interventions in the experimental group, both single-component (only web-implemented exercise) intervention  and multi-component (the web-implemented exercise intervention combined with other interventions) interventions  had a significant effect on reducing depression. According to the effect size, the multi-component interventions had a better effect than the single-component intervention. Based on the difference in interventions in the control group, we divided the control group into the empty control group  and the offline-exercise control group. Compared with the empty control group  and offline-exercise control group  separately, the web-implemented exercise interventions in the experimental group had a significant relieving effect on decreasing depression. However, when compared with the empty control group, the web-implemented exercise interventions in the experimental group had a better effect. When it comes to the intervention duration, the results of the sub-group analysis showed that the effect of the short-term  web-implemented exercise intervention  was better than that of the medium-term  web-implemented exercise intervention  and the long-term  web-implemented exercise intervention . For patients with different neurological diseases, the results showed that web-implemented exercise interventions had a significant effect on depression among patients with stroke , MS  and Cognitive impairment . No significant effect was observed in patients with PD .We performed subgroup analysis based on the type of interventions, type of patients, duration of interventions, and intervention components. I2 = 73%, P = 0.003) and VR exergame  had a significant relieving effect on anxiety. According to the effect size, the VR exergame interventions appeared to have a better-alleviating effect on anxiety than tele-exercise interventions. For contents of tele-exercise intervention, both face-to-face intervention  and offline delayed interventions  had a significant effect on reducing anxiety. For the components of interventions in the experimental group, both single-component (only web-implemented exercise) intervention  and multi-component (the web-implemented exercise intervention combined with other interventions) interventions  had a significant effect on reducing anxiety. According to the effect size, the multi-component interventions had a better effect than the single-component intervention. In terms of the intervention duration, the results of the sub-group analysis showed that the effect of the short-term  web-implemented exercise intervention  was better than that of the medium-term  web-implemented exercise intervention  and the long-term  web-implemented exercise intervention . For patients with different neurological diseases, the results showed that web-implemented exercise interventions had a significant effect on anxiety among patients with PD  and strokes . No significant effect was observed in patients with MS . Considering that only one study conducted the offline-exercise intervention in the control group, other studies were all blank controls, so we did not perform subgroup analyses based on the difference of interventions in the control group.This systematic review and meta-analysis has evaluated the effects of web-implemented exercise interventions on depression and anxiety in patients with neurological disorders by integrating 16 scientific studies involving a total of 963 participants. The review has shown that web-implemented exercise intervention significantly improves depression and anxiety in patients with neurological disorders. In addition, the effectiveness of the web-implemented exercise intervention is influenced by several factors, including web-implemented exercise intervention type, component, intervention duration, and patients with different neurological diseases. In terms of the type of web-implemented exercise interventions, the effect of tele-exercise is better than that of VR exergame on depression. While in relieving anxiety, the effect of VR exergame is better than that of tele-exercise. For the components of web-implemented exercise intervention, the effect of the multi-component intervention is better than that of the single-component on depression and anxiety. Additionally, based on the duration-related subgroup analysis, the effects of the web-implemented exercise intervention on both depression and anxiety were worse when the duration of interventions extends.Our result has demonstrated that web-implemented exercise interventions have a significant effect on the reduction of depression and anxiety in patients with neurological disorders. Exercise, as a non-medicine and non-invasive intervention, has been proven to reduce depression and anxiety in several RCTs , 47. It P = 0.89; anxiety: P = 0.54) and the fact that depression and anxiety may occur together make it difficult to distinguish the effect of web-implemented exercise interventions on depression and anxiety separately  has a better effect than the single-component web-implemented exercise intervention  on reducing both depression and anxiety symptoms in neurological patients. We have found that three studies involving single-exercise component intervention show no significant relieving effect on depression and anxiety symptoms in the experimental group, or even a lower effect in the experimental group than that in the control group –45. In cBased on the duration-related subgroup analysis, the result has indicated that the effect of the web-implemented exercise intervention on reducing depression and anxiety became less effective with the extension of intervention duration. This result is contrary to the results of a previous relevant meta-analysis. Huang et al.  have fouThe meta-analysis still has some limitations. First, most studies used depression and anxiety as the secondary outcomes, which might weaken the causal relationship between the web-implemented exercise intervention and depression and anxiety. Thus, further research is needed to directly prove the relationship between web-implemented exercise intervention and mental health outcomes . Second, this meta-analysis has included a variety of characteristics of web-implemented exercise interventions . The included studies involved different participant races and study designs, which may lead to moderate to high heterogeneity and lower quality. Finally, the limited number of included studies and the language restrictions may also cause bias on the integrated effect.This meta-analysis indicates that web-implemented exercise intervention can significantly relieve depression and anxiety symptoms in patients with neurological disorders. The current results suggest that short-term (≤6 weeks) and multi-component web-implemented exercise interventions have the better effect. In addition, tele-exercise has a better-relieving effect on depression, while VR exergame has a better-relieving effect on anxiety. It should be noted that the web-implemented exercise intervention is only a form of clinical therapy support. Except that, due to limitations and scarcity of studies involving the impact of web-implemented exercise interventions on mental health in neurological patients, more relevant studies are needed in the future. It is suggested to increase long-term follow-up and study biological mechanisms to further evaluate the effect of the web-implemented exercise intervention on mental health in neurological patients.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.SZ and XH: conceptualization and supervision. HZ and RW: methodology. HZ: formal analysis and writing—original draft preparation. HZ, RW, and ZK: investigation. ZK and JY: resources. HZ, RW, and XH: writing—review and editing. HZ and SZ: visualization. All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.


Key FeaturesThe British Regional Heart Study (BRHS) consists of an all-male cohort of 7735 participants aged 40–59 years, first recruited in 1978–80 and followed up over 40 years to 2018.The original focus of the BRHS was to investigate regional variations in cardiovascular disease (CVD) mortality across Britain, but the objectives widened to examine other key health outcomes related to CVD and associated with healthy ageing, such as physical function, disability, frailty, dental health, malnutrition and sarcopenia.The latest physical examination (40-year follow-up) of the cohort, conducted in 2018, hosted 667 men and another 1009 responded to postal questionnaires, all aged 78–99 years. This follow-up enhances prospective data at very advanced ages by building on the previous examination in 2010–12 at 71–92 years.The new measures conducted within this cohort’s 40-year follow-up include extended objective and subjective oral health measures, subjective appetite and malnutrition measures, and anthropometric measures associated with lower body extremity muscle mass.l.lennon@ucl.ac.uk] for more details.The BRHS has maintained existing collaborations and remains open to new collaborative projects. Please contact Lucy Lennon .The BRHS has over 600 peer-reviewed publications and has extensively published on areas of cardiovascular health and mortality, including established and novel risk factors. Recent publications include conditions and morbidity related to CVD and older age, such as frailty,The newly collected 40-year follow-up data in the 2018 cohort demonstrates a high level of self-reported ill health and disease, including CVD, as the cohort has advanced into very old ages (78–99 years). Moreover, the number of individuals that have edentulism (no teeth) and wear dentures is similar to national data from England’s Adult Dental Health Survey,The strengths and limitations of the BRHS 40-year follow-up cohort remain broadly similar to those previously highlighted.https://www.ucl.ac.uk/british-regional-heart-study]. In addition, new collaborations continue to be welcomed and data sharing enquiries should be directed to Lucy Lennon [l.lennon@ucl.ac.uk].Study details and accessibility to questionnaires, data collection document, and relevant publications can be found on [Ethical approval for this study has been obtained from National Research Ethics Service (NRES) Committee London—Central, reference number: MREC/02/2/91. Participants provided informed written consent to the investigation, which was performed in accordance with the Declaration of Helsinki.


Introduction: We aimed to evaluate the associations of sports participation with self-rated health and depressive symptoms in a nationally representative sample of Japanese adolescents.Methods: A questionnaire survey was conducted with 1,658 adolescents aged between 12 and 21 years. Sports participation levels were divided into high-frequency, moderate-frequency, low-frequency, and no-participation groups. Self-rated health was evaluated using a four-grade scale. Depressive symptoms were assessed using the Japanese version of the Patient Health Questionnaire-8. Other lifestyle behaviors were also surveyed. The associations of sports participation with self-rated health and depressive symptoms were examined using multiple logistic regression analysis.Results: The participants in the high- (odds ratio (OR), 0.45) and moderate-frequency  groups were less likely to self-report poor health than those in the non-participation group. By contrast, a U-shaped association was found between sports participation and depression, in which the participants in the moderate-frequency group  were less likely to have depressive symptoms. The OR for the high- (0.89) and low-frequency (0.91) groups were not significant. Furthermore, eating regular breakfasts, six or more days/week, and having shorter screen times of less than two hours/day were negatively associated with poor self-reported health and depressive symptoms.Conclusion: Moderate- to high-frequency sports activities are associated with a reduced risk of poor self-rated health among Japanese adolescents. However, only moderate-frequency activities were associated with a reduced risk of depression. Participation in optimal sports activities may effectively lower the risk of poor health in adolescents. Maintaining adolescent health is gaining attention because adolescents are exposed to health risk factors alongside the changes in social relations and exposure to online interactions . MoreovePhysical activity is associated with physical and mental health benefits in adolescents . In partPrevious studies in this field have had several limitations. First, they surveyed either self-rated health or mental health as the outcome, although the impact of sports participation may vary depending on health outcomes of interest . The difIn order to address these issues, we aimed to examine the associations among sports participation, self-rated health, and depressive symptoms among Japanese adolescents using a nationally representative sample.Data collectionThe Research Ethics Committee of the Graduate School of Medicine, Chiba University, approved this study . Anonymized data were obtained from the 2021 Sasakawa Sports Foundation National Sports-Life Survey of Children and Young People, which is a cross-sectional survey of a nationally representative sample of Japanese adolescents. We obtained only anonymous, data; therefore, informed consent was not required. The inclusion criterion was individuals aged 12-21 years living in Japan. There were no specific exclusion criteria. The participants were selected using a two-stage stratified random sampling method. Municipalities throughout Japan were stratified into 225 regions based on geographic areas and population sizes. The sample size for each region was allocated proportionally, according to the target age population. The participants from each region were selected using a Basic Resident Register and systematic random sampling. Data were collected using a self-reported questionnaire. Surveyors visited 3,000 participant homes and distributed paper-based questionnaires between June and July 2021. The participants were informed that the questionnaire was voluntary and anonymous. The surveyors revisited the homes and collected the questionnaires, after which consent was obtained by answering the questionnaire.Health statusSelf-rated health was measured using the question “How do you feel about your health?” The answers were “very healthy,” “healthy,” “not so healthy,” and “not healthy.” In the analysis, the four categories were dichotomized into healthy  and unhealthy  . DepressSports participationThe participants indicated the type and frequency of up to five sports activities performed over the past year. Sports activities included extracurricular school and club activities but did not include activities in school classes or events, such as field days. The type of sports participation was described in an open-ended manner. The frequency of each sports activity was reported as numbers per year, month, or week, depending on the frequency. The number of activities per year was then summed to calculate the total number of sports participants. The sports participation levels were classified into four categories: high frequency (≥seven times/week (corresponding to ≥364 times/year)), moderate frequency ), low frequency ), and non-participation (zero times/week (0 times/year)). The classification in this study followed the literature and physical activity recommendations for adolescents ,19.Participant demographicsSex, age, number of siblings, household income, breakfast consumption, screen time, and sleep duration were surveyed. The participants ages were divided into ≤17 years and ≥18 years. Answers to the number of siblings were dichotomized into 0 (single children) and ≥1 (those with siblings) . The queStatistical analysisCategorical variables are expressed as numbers and percentages. Continuous variables are shown as median and quartile values owing to the non-normal distribution of the data. The association between self-rated health and sports participation was examined using univariate logistic regression analysis, wherein self-rated health was the objective variable and sports participation was the explanatory variable. The odds ratios (ORs) for varying participation levels were calculated using the non-participation group as a reference. Associations between self-rated health and other demographics were also assessed. Furthermore, multivariate logistic regression analysis was performed to examine independent association, with self-rated health as the objective variable and sports participation and all demographics as explanatory variables. Similarly, the associations among depressive symptoms, sports participation, and other participant demographics were assessed using univariate and multivariate logistic regression analyses. Statistical significance was set at P < 0.05.The questionnaires were returned by 1663 adolescents (return rate: 55%). Of these, five were excluded because of incomplete answers regarding health status and sports participation. Data from the remaining 1,658 adolescents were used for analysis.Only 38 (2%) answered “not healthy,” while approximately one in five were classified in the unhealthy  category Table . The medAmong the four sports-participation groups, the proportion of unhealthy participants was the highest  in the non-participation group  in the non-participation group Table . A U-shaIn a nationwide survey of Japanese adolescents, this study showed that moderate- to high-frequency sports participation was associated with lower odds of poor self-rated health. Moderate-frequency sports participation was also associated with lower odds of depressive symptoms, whereas high-frequency sports participation was not. Furthermore, the participants with shorter screen times and regular breakfasts were less likely to report poor health. The results of our study highlight that optimal sports activities may vary depending on the target health outcomes. In addition, a multidimensional approach can effectively reduce the risk of poor health.In this study, the proportions of participants in the unhealthy category were lower than participants engaging in sports activities ≥three times/week than in those with no sports activities. However, the participation of <three times/week did not have a positive effect. Using general physical activity as the predictor, a recent meta-analysis showed that even a low frequency of physical activity had a small positive effect . HoweverWe found a U-shaped relationship between sports participation and depression, in which the proportions of participants in the unhealthy category were lower in the moderate-frequency groups but not lower in the high-frequency groups. Our study was similar to one done on Canadian adolescents, which highlighted the differential effects of sports participation on self-rated health and depression . AccordiThis study showed that shorter screen time and regular breakfast consumption were associated with reduced odds of poor self-rated health and depressive symptoms. Screen time is linked to sedentary time, visual problems, mental health, and communication skills and is one of the major determinants of adolescent health . BreakfaThe strength of this study is that participants were recruited using a nationwide random sampling method. Therefore, the results likely reflect the health statuses of overall Japanese adolescents. Another strength is that we surveyed both self-rated health and depressive symptoms, enabling evaluation of the differential associations between sports participation and the health outcomes. However, this study also had several limitations. First, a causal association between sports participation and health status could not be determined because of the cross-sectional nature of this study. Nevertheless, other longitudinal studies have shown that participation in sports during early adolescence predicts lower depressive and anxiety symptoms in late adolescence and young adulthood because it offers an opportunity for physical activity and community involvement . Second,Approximately 20% of the participants reported poor self-rated health. Furthermore, 10% had depressive symptoms. Moderate-to high-frequency sports activities are associated with a reduced risk of poor self-rated health among Japanese adolescents. However, only moderate-frequency activities were associated with a reduced risk of depression. Participation in optimal sports activities may effectively lower the risk of poor health in adolescents.


In terms of the postoperative functional outcomes assessed by the “Oswestry Disability Index” (ODI) functionality score, the model tends to favor the FL-guided injections over the US-guided injections . Finally, the US-guided and FL-guided injections did not show significantly different results in terms of postoperative complications . The subgroup analysis also did not demonstrate differences between the US-guided and FL-guided techniques in the following outcomes: vasovagal reaction, transient headache, and facial flushing. There was no significant difference between the US-guided and FL-guided injections for treating back pain in terms of postoperative pain intensity and complications. Still, the model tends to favor the FL-guided injections over the US-guided injections in terms of functionality.The objective of this study was to compare the outcomes of the ultrasound- and fluoroscopy-guided techniques in the management of back pain. Using PubMed, Scopus, and the Cochrane Library, we searched randomized controlled trials (RCTs) published before May 2023, which reported relevant data on the topic. The effectiveness of the ultrasound-guided (US-guided) and fluoroscopy-guided (FL-guided) approaches for back pain management was compared in terms of postoperative pain intensity, postoperative functional outcomes, and postoperative complications. Subgroup analyses were conducted for different postoperative periods. Eight studies were included in the analysis. There was no significant difference in post-procedural pain relief at one week, two weeks, one month, two months, and three months between the US-guided and FL-guided interventions for back pain management ,  Back pain is extremely common in the adult population, and it is one of the most frequent causes for patients to seek medical care ,2,3. TheThe success rate of fluoroscopy-guided injections is generally higher compared to blind techniques and can vary depending on several factors, including individual patient factors, underlying cause and mechanism of pain, location of pain generators, specific injection technique, skill, and experience of specialists performing this procedure . Howeverhttps://doi.org/10.17605/OSF.IO/CBQ82. We searched for RCTs, which studied the effects of the US-guided and FL-guided injections for back pain management, published before May 2023 in Scopus, PubMed, and the Cochrane Library  study design: “randomized controlled trials” (RCTs); (b) age: 18 years and older; and (c) procedures: interventions for back pain management performed either under US and/or fluoroscopic guidance. We considered studies published in the English language. We excluded studies if they included (a) pediatric patients; (b) study designs other than RCT; or (c) poorly described methodology or inadequately reported findings. The primary outcome of our meta-analysis is post-procedural pain intensity. The secondary outcomes were functional outcomes (ODI/NDI) and postprocedural complications.2 statistic was used to estimate the heterogeneity.Data extraction disputes were resolved via discussion among the authors. In case of further disagreements, an author not involved in data extraction was consulted. We extracted the following data from RCTs in the data table : 1st autWe used the Cochrane Risk of Bias tool 2  to checkWe initially identified 380 articles that matched our search criteria . Eight aThe included studies were published between 2012 and 2018. The studies presented the results of pain measurements before the injection, at one and two weeks, and one, two, and three months post-operation, while ODI/NDI functionality scores were measured at baseline, two weeks, and one and three months. Immediate post-injection complications such as vasovagal reaction, transient headache, and facial flushing were the common reactions encountered by a minority of patients. We found one publication that studied this procedure . The “USIt was found that “US-guided epidural steroid injections” demonstrated a similar analgesic effect compared with “FL-guided injections” . There wThe authors found significant improvements in pain and disability index within both groups compared to the baseline scores and no difference between the groups . It was One study assessed US and “FL-guided caudal steroid injection” for the management of post-laminectomy pain . “CaudalThere was no difference in pain reduction between the US and FL groups. The success rate of the US-guided interventions was 85%. The procedural time was shorter in the US than in the FL group, and the radiation dosage in the US group was lower than in the FL group. There were no serious complications reported in any of the patients in either group. Therefore, US guidance might be a safe, feasible method that requires less time and is associated with less radiation to reach the same results as the FL-guided method .It was shown that there were no significant improvements in pain and ODI scores at 2 weeks and 3 months in both groups, and the intergroup difference in scores . The neeThe study conducted by Soneji did not find any notable differences in accuracy, efficacy, or patient satisfaction between these two image-guided techniques for SIJ injections .p = 0.91, I2 = 0%.Pain intensity is shown in the forest plot below . The modp = 0.02, I2 = 0%   anda (2016) ) did notGiven the nature of the procedure, a certain degree of risk of bias was present due to the lack of double blinding. This has seriously affected the methodological quality of the studies. Based on the Cochrane risk of bias assessment, three studies had “some concerns” about the risk of bias, and four had a “high” risk of bias . Five ouIn this SR&MA, we included eight RCTs, which compared ultrasound-guided and fluoroscopy-guided techniques for back pain management. Using ultrasound guidance alongside fluoroscopic confirmation could be a viable option for visual guidance for various interventions in back pain management ,17,18,19There were no significant differences found in the reduction in back pain at one week, one month, and three months following the interventions. Regarding postoperative functional outcomes assessed by the ODI and NDI, there was no difference between the two groups at one month, and three months after intervention. The rate of postoperative complications also did not differ significantly between US-guided and FL-guided techniques. Subgroup analysis that was performed for various outcomes  did not differ significantly between US-guided and FL-guided injections ,17,18,19A recent meta-analysis compared US-guided injections (intervention group) with fluoroscopy- or computer tomography (CT)-guided injections (control group) in the spinal nerves . SimilarObservational studies showed similar results. Thus, a study comparing “US-guided selective nerve root block”, “FL-guided interlaminar epidural block”, and “FL-guided transforaminal epidural block” for the management of radicular pain in the lower cervical spine demonstrated that although both the VNS and “neck disability index” improved within the groups at 1, 3, and 6 months in all groups, there were no differences between the groups. Moreover, the treatment success rate at all time points was not significantly different between the groups. US-guided interventions required a shorter duration and resulted in similar pain reduction and functional improvement. Thus, a US-guided technique might be considered for epidural steroid injection .Similar results were yielded by another retrospective observational study of 54 patients with facet syndrome . One monAnother observational study comparing US- and FL-guided caudal epidural steroid injection for the management of unilateral lower lumbar radicular pain also yielded similar results . The stuUltrasound could be used with fluoroscopic confirmation for guiding sacroiliac joint injections in patients with SIJ arthritis. Both FL-guided and US-guided approaches for different methods of SIJ innervation are well described in a review article . Even ifHartung et al. found that using ultrasound for sacroiliac joint (SIJ) arthropathy resulted in 40% of injections being administered intraarticularly . RemarkaGiven the absence of radiation exposure, lower cost, and convenience, US-guided techniques might be preferred for patients, doctors, and healthcare in general. The current guidelines for interventional management of chronic back pain recommend using fluoroscopic guidance. A qualitative review of studies on intradiscal injections for low back pain management revealed that almost 62% of the studies on the topic had performed the procedure under FL guidance (with or without comparators), and another 8.8% combine the FL and CT approaches . AnotherThis systematic review has several major limitations. Only eight studies with relatively small sample sizes matched the inclusion criteria and were meta-analyzed. There was heterogeneity in the patient populations, the anatomical localization of back pain, and interventions included in the meta-analysis. Additionally, some studies employed an “ultrasound-assisted” approach, where ultrasound was used to locate the injection site, while others utilized dynamic guidance during the procedure. Given the nature of the intervention, there was a serious risk of bias in the included studies due to the lack of blinding. Finally, while there was no statistically significant difference observed between the two techniques, none of the included studies had a no-intervention arm to assess the effectiveness of the injections for low back pain. Despite these limitations, there was no evidence that US-guided techniques were overall inferior to FL-guided techniques. The advantages of the US include relative simplicity of performance, absence of radiological exposure, and continuous real-time needle guidance. However, while ultrasound guidance can decrease radiation exposure and enhance the visualization of soft tissues and vascular structures, there are a few disadvantages . The quaThere were no significant differences between US-guided and FL-guided injections in reducing back pain intensity and complications at one month and three months after intervention. However, the model tends to favor the FL-guided injections over the US-guided injections in terms of functionality. Given the limitations of this meta-analysis, future RCTs are warranted to establish solid evidence on relevant outcomes for using these two techniques for back pain management.


Cefiderocol (FDC) is a siderophore cephalosporin now recognized as a new weapon in the treatment of difficult-to-treat-resistant (DTR) Gram-negative pathogens, including carbapenemase-producing enterobacterales and non-fermentative Gram-negative bacilli (GNB). This article reports our experience with an FDC-based regimen in the treatment of 16 extremely severe patients  infected with DTR GNB. Our case series provides detailed insight into the pharmacokinetic profile and the microbiological data in real-life conditions. In the narrative review, we discuss the interest of FDC in the treatment of non-fermentative GNB in critically ill patients. We reviewed the microbiological spectrum, resistance mechanisms, pharmacokinetics/pharmacodynamics, efficacy and safety profiles, and real-world evidence for FDC. On the basis of our experience and the available literature, we discuss the optimal FDC-based regimen, FDC dosage, and duration of therapy in critically ill patients with DTR non-fermentative GNB infections. Pseudomonas aeruginosa (CR-Pa), Acinetobacter baumannii (CR-Ab), and Stenotrophomonas maltophilia (Sm), also called difficult-to-treat-resistant (DTR) GNB  for qualitative and quantitative variables respectively.VAP: ventilation-associated pneumonia; SSTI: skin and soft tissue infection; c-UTI: catheter-related urinary tract infection; CR: carbapenem-resistant; CR-Ab: carbapenem-resistant The median duration of FDC treatment was 8 days [7–13.5] . Source The MIC for FDC was tested whenever possible throughout the relapses . We obseA. baumannii and cefiderocol-resistant P. aeruginosa. In Case 16, a prolonged treatment course was decided (more than seven days) with nebulized colistin as a third antibiotic.A combination therapy was used in 11 out of 30 episodes of infection (37%). Colistin was administered (nebulized or intravenously) in 7 episodes, whereas tigecyclin and ciprofloxacin was administered in 3 episodes . In patiC. difficile-associated colitis, were also observed. Fever was observed in two patients, which may have been related to FDC but did not require premature discontinuation. A hypersensitivity reaction was suspected in one patient (Case 6), who had a rash without hypereosinophilia, which was unlikely to be due to FDC (it appeared just before treatment initiation), and it disappeared after EOT. Neurological complications were observed in nine patients. As this occurred in sedated patients, the severity could not be clearly established, but it could have resulted in persistent hyporeactive delirium (Case 16). We did not observe seizures.The most frequent adverse events were hepatobiliary and neurological complications . They wen = 4) or IHD (n = 4) (TDM was performed at least once in 12 patients (75%), 8 of whom were placed under RRT using either CVVHD ( (n = 4) . The med (n = 4) . Two patA. baumannii, P. aeruginosa, S. maltophilia, and P. putida. The conditions of the treated patients were extremely severe, with a median ICU stay of 60 days. Although clinical cure at EOT was approximately 70% (11/16), relapses and superinfections were common (9/11). Relapse required a new antimicrobial regimen including FDC. Patients survived for at least one year from hospital stay in 62.5% (10/16) of cases. Despite a large variation in kidney function between glomerular hyperfiltration and renal replacement therapy with or without ECMO, the trough concentrations were within the usual range, which suggests that the recommended doses were adapted to the most severe patients. We report here the results of FDC treatment on a cohort of very severe ICU patients treated for severe late-onset nosocomial infections, mainly VAP, due to difficult-to-treat Nevertheless, our data suggest that reliance on TDM remains paramount because of large intra- and interindividual variability to optimize therapy, especially in the most severe patients  under RRA. baumannii, has been found in vitro to be associated with bacterial regrowth after FDC exposure [The particularly high incidence of persistent colonization and relapse in our FDC-treated patients raises the question of the emergence of resistance mechanisms during treatment . As descexposure . In our The toxicity of FDC has been widely assessed in randomized controlled trials and preclinical studies ,44, withConsidering the high rate of relapses/superinfections, FDC-based regimens should be optimized. FDC heteroresistance with frequent bacterial regrowth after FDC exposure presents a sound argument for combination therapy . HoweverP. aeruginosa [In our cases, relapses and superinfections were not influenced by the use of combination therapy or adjunctive nebulized colistin. A firm conclusion is limited by the small number of patients enrolled and requires further studies. The mean duration of therapy was 8 days, in accordance with the guidelines. The high rate of persistent colonization and relapse may suggest that the treatment was stopped too early. Indeed, in a randomized controlled trial, Bouglé et al. failed to demonstrate the non-inferiority of an 8-day antimicrobial regimen over a 15-day antibiotic regimen on mortality or recurrence in patients with VAP due to ruginosa . On the This narrative review and personal experience focused on the use of FDC-based regimens for the treatment of infections caused by DTR Gram-negative non-fermentative bacilli in critically ill patients. The use of FDC as a last resort option appeared to be safe in the most critically ill patients, with a high rate of clinical success and a good survival rate but a significant risk of relapses and superinfections. The dosing recommendations allow acceptable tolerability and acceptable concentrations to be achieved in routine practice, although the risk of neurotoxicity needs further investigation. Further data are needed on the optimal duration of therapy and the use of combination antibiotic therapy or adjunctive nebulized antibiotics.


There is a bidirectional effect between sleep disorders and Mediterranean diet (MED), but the joint effect of MED and sleep disorders on mortality is unclear. The aim of this study was to investigate whether there is a synergistic effect of adherence to MED and sleep disorders on all-cause and cause-specific mortality.The study included 23,212 individuals in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2014. A 9-point evaluation score, alternative Mediterranean diet (aMED) index was used to assess adherence to MED. Sleep disorder and hours of sleep were assessed by structured questionnaires. Cox regression models were used to assess the relationship between sleep disorders, aMED and all-cause mortality, cause-specific mortality . The interaction effect of sleep disorders with aMED on mortality was further assessed.Results showed that participants with lower aMED and presence of sleep disorders had significantly higher risk of all-cause mortality and cardiovascular-related mortality . A significant interaction effect was found between aMED and sleep disorders on cardiovascular mortality (p for interaction = 0.033). No significant interaction existed between aMED and sleep disorders on all-cause mortality (p for interaction = 0.184) and cancer-related mortality (p for interaction = 0.955).Poorer adherence to MED and sleep disorders synergistically increased long-term all-cause mortality and cardiovascular mortality in NHANES population.The online version contains supplementary material available at 10.1186/s12889-023-15870-x. Numerous studies have confirmed that poor dietary habits may increase the risk of chronic diseases and mortality risk in the long term . The potOn the other hand, there are growing evidences on the relationship between sleep disorders and all-cause mortality, but the conclusions are controversial. The general opinion is that both shorter and longer sleep duration increase the risk of mortality and that sleep duration shows a U-shaped relationship with long-term mortality  In additIn summary, the effect of MED and sleep on death in the whole population needs to be further clarified. Furthermore, given that diet and sleep can affect each other, it is unclear if lower adherence level to MED can interact with sleep disorders for long-term mortality. Therefore, the article investigated whether there is a synergistic effect of adherence to MED and sleep disorders on all-cause and cause-specific mortality in U.S. population.https://www.cdc.gov/nchs/nhanes/irba98.htm) and informed consent was obtained from all participants before enrollment (https://www.cdc.gov/nchs/nhanes/genetics/genetic_participants.htm#print). The study was conducted in accordance with the Declaration of Helsinki. Data obtained from five cycles (every two years) from 2005 to 2014 were included in this study. Follow-up data on death status, death date and causes of death were linked to the National Death Index (NDI) (https://www.cdc.gov/nchs/ndi/about.htm). The NDI, maintained by NCHS, is published annually and provides epidemiologists with complete population-wide mortality data for the U.S.[NHANES is a national, cross-sectional survey that assesses the health and nutritional status of the U.S. population. Based on a complex sampling design, the population included in this survey is representative of the U.S. population of all ages. The survey includes interview questionnaires, standardized physical examinations, and laboratory tests  The surv the U.S. The inclRelevant dietary information was collected from the 24-h dietary recall questionnaires in the NHANES database. The first 24-h dietary recall questionnaires were completed in a mobile examination center (MEC) (Day 1), and the second 24-h dietary recall within 10 days of the MEC assessment was completed by telephone follow-up (Day 2). We used the two days of 24-h dietary recall data to assess the average dietary intake over 2 days. Adherence to the MED was calculated by two steps. First, 24-h dietary recall data was linked to United States Department of Agriculture, Food Patterns Equivalents Database to convert different foods, beverages into equal amounts of food pattern components . In the Baseline and sociodemographic data, laboratory tests, medical condition data, and other dietary recall data were collected from the population. Baseline and sociodemographic data included age, sex, race, education level, marital status, annual household income, family poverty income ratio (PIR), smoking status, body mass index (BMI), and mean systolic/diastolic blood pressure (SBP/DBP). PIR was a ratio of monthly family income to the poverty threshold specific to family size, released by Health and Human Services poverty guideline. Smoking was defined as smoking fewer than 100 cigarettes in life or smoking at the time of survey. Laboratory tests included triglycerides (TG), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), fasting glucose, glycated hemoglobin A1c (HbA1c), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), and estimated glomerular filtration rate (eGFR). History of previous hypertension, diabetes mellitus, congestive heart failure (CHF), coronary heart disease (CHD), and stroke were included from medical condition questionnaires. Previous hypertension was defined as self-reported physician diagnosis of hypertension, or oral antihypertensive drugs or elevated mean blood pressure (systolic ≥ 130 and/or diastolic ≥ 85 mmHg). Diabetes was defined as meeting any of the following items: self-reported physician diagnosis of diabetes, self-reported use of insulin or oral hypoglycemic drugs, a fasting glucose concentration > 126 mg/dL, HbA1c ≥ 6.5%, and Oral Glucose Tolerance Test (OGTT) ≥ 200 mg/dL. The rest of the medical history was directly collected through questionnaires. Other dietary intake variables included total calorie intake, carbohydrate intake, protein intake, fat intake, dietary fiber intake, added sugar intake, monounsaturated fatty acid, polyunsaturated fatty acid, saturated fatty acid intake, electrolytes intake, caffeine intake, and fresh water intake.Enrolled patients were followed up until December 31, 2015. Mortality status, causes of death, and follow-up time were determined based on the NDI, which can be downloaded from NCHS website. Causes of death were coded according to ICD-10.The study outcomes included mortality from all causes, cancer (codes C00-C97), and CVD . The median follow-up time for all patients was 111.6 months.http://www.R-project.org, R Foundation). The statistical analyses followed the criteria from NHANES, which takes into account the complex sampling design . All analyses needed to be weighted to represent the U.S. population. We calculated the weighted estimates according to NHANES analytic guidelines . Baseline information was described among three aMED groups. Continuous variables are expressed as survey-weighted means (95% CI). Categorical variables were expressed as survey-weighted percentage (95% CI). Differences in continuous variables among groups were analyzed by survey-weighted linear regression (svyglm). Differences in categorical variables were analyzed by survey-weighted Chi-square test (svytable). Cox proportional risk regression models were used to calculate HRs and 95% CIs for sleep disorder, and aMED on all-cause, cardiovascular mortality and cancer mortality. Model I was adjusted for age, sex, and race ; model II was further adjusted for education level , marital status , and family PIR; model III was further adjusted for BMI, smoking status, total energy intake, and comorbidities including diabetes mellitus, hypertension, CHF, CHD, and stroke. Patients were further grouped according to aMED and sleep disorder (presence or absence), and Cox proportional risk regression was performed to analyze the relationship with mortality. Interaction effect of sleep disorder with aMED on mortality outcomes was inspected by likelihood ratio test, and two-sided P for interaction of 0.1 were considered statistically significant. Survival curves for the aMED and sleep disorder subgroups were plotted using the Kaplan Meier method and examined by the log-rank test. In addition, restricted cubic spline (RCS) plots were used to assess the dose-response relationship between aMED score and mortality risk. Multiple imputations with chained equations were applied to impute missing values. All analyses were repeated with the complete data to examine the robustness of the results. Two-sided P values of 0.05 were considered statistically significant.All analyses were performed with the statistical package R  were of cardiovascular causes and 722 (23.4%) were due to cancer. Cox proportional risk regression models were used to calculate the association of aMED, sleep disorders with all-cause mortality, and cause-specific mortality. After fully adjusting for covariates (model III), it suggested that lower aMED significantly increased the risk of all-cause mortality  and cardiovascular mortality , compared with higher aMED group. When further analyzing aMED as a continuous variable, a lower aMED score was associated with a higher risk of all-cause mortality . The presence of sleep disorders significantly increased the risk of all-cause death and cardiovascular mortality . However, lower aMED did not significantly increase the risk of cancer mortality , and sleep disorders did not significantly increase the risk of cancer mortality either   (Fig. The dose-response relationship between aMED and all-cause mortality and cardiovascular mortality was further assessed by RCS curves Fig. , and a mThis study confirms for the first time that the combined presence of poor adherence to the MED and sleep disorders synergistically increases all-cause and cardiovascular mortality, and there was a significant interaction effect between aMED and sleep disorders on cardiovascular mortality, with a higher relative risk of mortality among those with poor adherence to the MED and sleep disorders.A large number of studies have examined the correlation between diet habits, sleep disorders, and mortality. Poor dietary habits are strongly associated with the risk of developing chronic diseases and long-term mortality . Poor diMeanwhile, MED and sleep disorders are closely related and influence each other. Our analysis found a significant interaction between aMED and sleep disorders for cardiovascular mortality. For people with sleep disorder, the risk of cardiovascular death was significantly higher with decreased aMED scores, while this trend was not found in the population without sleep disorders. The MED may have a more prominent role in contributing to cardiovascular events in the sleep-disordered population. A previous cohort study also confirmed that adequate sleep, in addition to maintaining a traditional healthy lifestyle such as a healthy diet and regular physical activity, can additionally reduce the risk of cardiovascular disease . This maOur study further explored which dietary components play a key role in the relationship between the MED, sleep disorders, and mortality outcomes. Fruits, whole grains, legumes, and alcohol consumption significantly interacted with sleep disorder for cardiovascular mortality. Studies confirmed that people with sleep disorders are often deficient in tryptophan, melatonin, B vitamins, calcium, and trace elements such as selenium and magnesium , 50. WhoThe strengths of the study can be summarized as follows: This is the first study investigating the joint effect between adherence to MED and sleep disorders on long-term mortality. To strengthen the reliability of the findings, potential covariates were adjusted, and the aMED was treated as continuous and categorical variables. By applying a quantified score to assess the adherence of MED, we explored the non-linear relationship between aMED and mortality outcomes, and found that in the population with sleep disorders, the risk of death significantly increases when aMED is less than 4.Our study has some limitations. Limited by the study design of NHANES, the assessment of sleep disorders was only from self-reported questionnaires, without investigating objective sleep patterns, and medical records were lacking, which may have introduced risk of misclassification of sleep disorders, and hindered further analysis of sleep disorder-related parameters, such as insomnia severity, excessive daytime sleepiness, and sleep apnea. In addition, despite efforts to minimize data collection bias, there may have been some discrepancies between the reported dietary information and participants’ actual habits, which could have potentially influenced our results. Meanwhile, information about medical treatment for sleep disorder was lacking. which was not adjusted for in our analyses.Poor adherence to the MED and sleep disorders jointly increased long-term all-cause mortality and cardiovascular mortality in the U.S. population. There was a significant interaction effect between aMED and sleep disorders on cardiovascular mortality.Below is the link to the electronic supplementary material.Supplementary Material 1