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Supplementary Materials | The following supporting information can be downloaded at: Click here for additional data file. | PMC9961050 | ||
Author Contributions | I.V., L.R., M.P. and A.V. designed the study; I.V. enrolled participants, collected and analyzed the data and drafted and revised the manuscript; L.R. performed orthopedic evaluation; L.R. and M.P. helped revise the manuscript. All authors have read and agreed to the published version of the manuscript. | PMC9961050 | ||
Institutional Review Board Statement | This study was performed in accordance with the Declaration of Helsinki and was approved by the University of Tartu Research Ethics Committee (No. 298/T-10, 18.11.2019). This study was registered at | PMC9961050 | ||
Informed Consent Statement | Informed consent was obtained from all subjects involved in the study. | PMC9961050 | ||
Data Availability Statement | The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. | PMC9961050 | ||
Conflicts of Interest | The authors declare that they have no competing interests. | PMC9961050 | ||
Abbreviations | PTE, musculoskeletal injury | BMI, body mass index; CI, confidence interval; CON, control; EqArea, equivalent area; H/Q, hamstring to quadriceps; INT, intervention; MSI, musculoskeletal injury; PP, prevention program; PTE, peak torque in extension; PTF, peak torque in flexion; RR, relative risk; SD, standard deviation. | PMC9961050 | |
References | injuries | Flow of participants through the study.Baseline anthropometric characteristics.Data are mean ± SD; INT, intervention group; CON, control group.Injury incidence.INT, intervention; CON, control; RR, relative risk; CI, confidence interval.Number of injuries.INT, intervention; CON, control.Motor performance and psychosocial status.Data are mean ± SD. EqArea, equivalent area; PTE, peak torque in extension; PTF, peak torque in flexion; H/Q, hamstring to quadriceps. After Bonferroni correction, the necessary value for a significant difference was | PMC9961050 | |
Background | CAD | CORONARY ARTERY DISEASE, CAD | Since myocardial work (MW) and left atrial strain are valuable for screening coronary artery disease (CAD), this study aimed to develop a novel CAD screening approach based on machine learning-enhanced echocardiography. | PMC10176743 |
Methods | This prospective study used data from patients undergoing coronary angiography, in which the novel echocardiography features were extracted by a machine learning algorithm. A total of 818 patients were enrolled and randomly divided into training (80%) and testing (20%) groups. An additional 115 patients were also enrolled in the validation group. | PMC10176743 | ||
Results | CAD | CARDIAC EVENTS, CAD | The superior diagnosis model of CAD was optimized using 59 echocardiographic features in a gradient-boosting classifier. This model showed that the value of the receiver operating characteristic area under the curve (AUC) was 0.852 in the test group and 0.834 in the validation group, with high sensitivity (0.952) and low specificity (0.691), suggesting that this model is very sensitive for detecting CAD, but its low specificity may increase the high false-positive rate. We also determined that the false-positive cases were more susceptible to suffering cardiac events than the true-negative cases. | PMC10176743 |
Conclusions | CAD | CAD | Machine learning-enhanced echocardiography can improve CAD detection based on the MW and left atrial strain features. Our developed model is valuable for estimating the pre-test probability of CAD and screening CAD patients in clinical practice.
| PMC10176743 |
Keywords | PMC10176743 | |||
Introduction | CAD, death | DISEASES, CORONARY ARTERY DISEASE, CAD | Early diagnosis of coronary artery disease (CAD), a leading cause of death worldwide [The myocardial work (MW) is one of the newly developed noninvasive techniques for CAD diagnosis, which has an assessment function of deformation and afterload that provides incremental value to the evaluation of cardiac function [Although the novel noninvasive tools hold new promise for screening CAD patients, they are not perfect, because they lack the computational models that can combine these new methods to improve diagnostic performance in their clinical application. AI technology has been widely used to diagnose, treat, and manage different diseases [ | PMC10176743 |
Methods | PMC10176743 | |||
Patients | CAD, stenosis | STENOSIS, CAD | This prospective clinical trial (NCT03905200, registered on 5 April 2019) included 958 cases diagnosed as clinically suspected CAD by coronary angiography in Beijing Hospital, Beijing, China. The patients with CAD were diagnosed by coronary angiography, which showed ≥ 50% stenosis in one or more coronary arteries [ | PMC10176743 |
Echocardiography | CONTRACTION | The instruments for echocardiography included Vivid E9 and Vivid E95 ultrasound systems (GE Vingmed Ultrasound, Horten, Norway). The baseline echocardiography for the admitted patients was implemented prior to their coronary angiography. The original data of echocardiography images were stored in DICOM format. EchoPac software (EchoPAC 204, GE Vingmed Ultrasound) was used to analyze conventional, MW, LA indices offline. The performance guidelines of echocardiography were the American Society of Echocardiography guidelines [MW indices were determined by the EchoPAC software, which had a pressure–strain loop area module made from non-invasively estimated LV pressure curves and LV strain. Peak systolic LV pressure was assumed to be equal to the peak brachial cuff systolic blood pressure that was measured simultaneously at the echocardiography examination, which has been reported previously [In addition, the measurement of LA strain was performed using the instrument of AFI LA (EchoPAC 204, GE Vingmed Ultrasound), in which zero strain was defined by the automatic R-wave trigger on the electrocardiogram. EchoPac 204 is equipped with a software package for evaluating LA strain based on the strain values in three phases: reservoir strain in systole (LASr), conduit strain in early diastole (LASct), and contraction strain in late diastole (LAScd). | PMC10176743 | |
ML classifiers | Recently, ML-based research methods have been widely used in clinical diagnostic studies [ | PMC10176743 | ||
Model training | CAD | CAD | The tenfold cross-validation test was also applied for the model training. The CAD data set was randomly divided into two parts (80% training data set and 20% testing data set). A model for CAD prediction was built by extracting the imaging and clinical features with ML methods. | PMC10176743 |
Feature selection | The imaging and clinical features were reduced and selected using different strategies to overcome the problem of model overfitting. The importance of variables was evaluated in each classifier. For example, the correlation coefficients ( | PMC10176743 | ||
Training data set optimization | CAD | CAD | Since the randomly divided training data sets also influence the classifier accuracy, we selected a group of high-performance training data sets after hundreds of cross-validation tests. The intersection of various training data sets with an accuracy of around 80 ~ 85% was selected as a standard to build the final training data set for CAD detection. The framework of the proposed model for diagnosing CAD is illustrated in Fig. Framework of the proposed model for diagnosing CAD. A stepwise workflow to optimize the predictive learning model by screening and recomposing features, selecting superior classifiers, and identifying the convergent training data set. | PMC10176743 |
Model validation | Additional 115 patients recruited from September 2021 to July 2022 were enrolled as the validation data set (out from the cross-validation test), which was used for selecting classifiers and validating the model performance. | PMC10176743 | ||
Prognostic follow-up | death | BLIND | The follow-up information was obtained through clinical visits or telephone calls by an investigator blind to clinical factors and coronary angiography data. All-cause mortality and cardiovascular hospitalization composited the study endpoint. The death documentation was obtained from hospital medical records and phone conversations with family members. Furthermore, the cause of death was adjudicated by a review of medical records. The follow-up data were obtained up to June 2022. The overall completeness of follow-up was 74.9%. The mean follow-up time was 2.6 years (0.8–3.5 years). | PMC10176743 |
Statistical analysis | The data of the continuous variables with normal distribution were expressed as mean ± standard deviation, and those without normal distribution were expressed as median (interquartile range). Chi-square or Fisher’s exact tests was used for comparing the difference between categorical variables, while the comparison of continuous variables was performed using the | PMC10176743 | ||
Results | PMC10176743 | |||
Discussion | CAD, myocardial ischemia, obstructive CAD | CORONARY STENOSIS, MYOCARDIAL ISCHEMIA, CAD, STENOSES | This might be the first study on the diagnostic model of CAD using novel echocardiography tools (MW and LA strain) integrated with ML models. This superior CAD detection model showed a value of ROC AUC (0.852) with a sensitivity of 0.95 and specificity of 0.69 in the test group, while the ROC AUC value was 0.834 in the validation data set. Our model was very sensitive in detecting CAD patients. We found that MW and LA strain-based ML approach has great potential to screen CAD patients.The application of imaging techniques in clinics plays an important role in the diagnosis and prognosis of CAD, reducing the morbidity and mortality of CAD patients. Due to its feasibility and reliability, echocardiography is still the most commonly used imaging tool for diagnosing heart problems. Traditionally, the conventional echocardiographic parameter used to evaluate the presence or absence of CAD has mainly been segmental wall motion abnormalities by visualization using nude eye observation, which may miss some subtle abnormalities [A total of 818 patients were enrolled in this study. The median sample size in the previous reports is approximately 350 [Coronary angiography is generally considered a gold standard for CAD diagnosis. However, coronary angiography is complex, costly, and has side effects. In contrast, the echocardiography-based methods were suitable for almost all patients, but it has been rarely reported about the clinical applications of the models that can combine novel echocardiographic methods, as mentioned above, to improve diagnostic performance. To this end, our ML model provides an approach to solving this problem. Our model demonstrated its sensitivity of 0.952 and specificity of 0.691 in the test group and its AUC of 0.852. Although the accuracy of our model was similar to that of other studies, it is notable that the inclusion criteria in our study were broader than those in the most published studies, which were closer to real-world conditions, suggesting a high sensitivity of our model, which might be used for screening the CAD patients in clinics to allow early diagnosis and treatment.Coronary angiography mainly reflects anatomical stenoses, but it cannot reflect functional problems, while strain can partly reflect functional problems. Strain is mainly a reflection of myocardial function rather than the anatomic coronary stenosis itself. In clinical practice, many patients had myocardial ischemia without obstructive CAD [ML algorithms have been widely used for analyzing medical images [ | PMC10176743 |
Limitations | This study had several limitations. It was a single-center study due to its data collected from the same medical system. In this study, we enrolled patients who underwent coronary angiography with typical myocardial ischemia-related symptoms or positive results of examinations. In addition, a single echocardiogram vendor and post-processing algorithm were applied. All of those may increase the instability of the model, resulting in low generalization of the results. Therefore, further studies with multi-center data will be considered, in which the method of an adaptive learning process could be included, enabling the model to update when inputting new samples automatically. The semi-automatic speckle tracking analysis was another limitation of our study. Because of this, the different physicians' subjective opinions may also influence the final prediction. The difficulty to recognize the epicardial or endocardial border by EchoPac (in case of processing low-quality images) was also a critical issue in our model, which could bring certain biases to the results. To address this issue, it is necessary to develop an automatic image quality control and tracing technique to analyze echocardiogram data. To effectively reduce subjective errors, some efforts should be made to reduce user intervention in image feature extraction and classification analysis. Because our overall follow-up time was limited, we have only discovered a few trends thus far. We will continue to follow up with these patients. A risk stratification assessment model will be established based on the prognosis of those patients. | PMC10176743 | ||
Conclusions | CAD | CAD | Our study demonstrated the following benefits of our model in CAD diagnosis: (1) good diagnostic performance in screening CAD patients, confirmed in the validation group; and (2) the predictive function of our model only requires the non-invasive echocardiographic and some commonly used clinical features. In summary, our novel model could provide a more efficient and non-invasive method for screening and diagnosing CAD in clinics. | PMC10176743 |
Acknowledgements | The authors thank Mrs. Jiangtao Wang and Mr. Zhicheng Zhu at the GE Company for their technical support. These individuals did not influence the study management or the writing of this article. | PMC10176743 | ||
Author contributions | YG, CX, YW, and FW are the major contributors to writing the manuscript. YZ, HZ, JM, GL, and YG analyzed the echocardiograms. XW, HZ, XM, and CY collected the patient information. YW, CX, and XW revised the manuscript carefully. FW conceived the study and supervised the project. All authors read and approved the final manuscript. | PMC10176743 | ||
Funding | The study was supported by the National High-Level Hospital Clinical Research Funding (Grant No. BJ-2022–117), the National Key R&D Program of China (2020YFC2008100/2020YFC2008106), and the Key Industrial Innovation Chain Project in Shaanxi Province of China (2023-ZDLSF-21). | PMC10176743 | ||
Availability of data and materials | The data sets used and/or analyzed during the current study are available from the corresponding author upon reasonable request. | PMC10176743 | ||
Declarations | PMC10176743 | |||
Ethics approval and consent to participate | This study was approved by the ethics committee of Beijing Hospital (reference number: 2020BJYYEC-021–02). Our study is a post-hoc analysis of data from an IRB-approved prospective clinical trial (NCT03905200). Informed consent was obtained from all individual participants included in the study. | PMC10176743 | ||
Consent for publication | Not applicable. | PMC10176743 | ||
Competing interests | The authors declare that they have no competing interests. | PMC10176743 | ||
References | PMC10176743 | |||
Background | RHEGMATOGENOUS RETINAL DETACHMENT | This study evaluated the vascular changes in the macular and peripapillary regions before and after silicone oil (SO) removal in patients with rhegmatogenous retinal detachment. | PMC10053480 | |
Methods | tamponade | This single-center case series assessed patients who underwent SO removal at one hospital. Patients who underwent pars plana vitrectomy and perfluoropropane gas tamponade (PPV + C | PMC10053480 | |
Results | SO tamponade | Fifty eyes were administered SO tamponade, 54 SO tamponade(SOT) contralateral eyes, 29 PPV + C | PMC10053480 | |
Conclusions | SO tamponade | SVD and SPD are decreased during SO tamponade and increased in the macular region of eyes that underwent SO removal, suggesting a possible mechanism for reduced visual acuity during or after SO tamponade. | PMC10053480 | |
Trial registration | Registration date: 22/05/2019; Registration number, ChiCTR1900023322; Registration site, Chinese Clinical Trial Registry (ChiCTR). | PMC10053480 | ||
Supplementary Information | The online version contains supplementary material available at 10.1186/s12886-023-02868-7. | PMC10053480 | ||
Keywords | PMC10053480 | |||
Introduction | tamponade, RRD, ocular trauma, SPD, retinal detachment, macula-off rhegmatogenous | PROLIFERATIVE VITREORETINOPATHY, RETINAL TEARS, RETINAL DETACHMENT, RETINA | The combination of vitrectomy and silicone oil (SO) tamponade is widely used for treating complex retinal detachment accompanied by proliferative vitreoretinopathy, large retinal tears, and ocular trauma [Changes in macular and peripapillary microcirculation can affect vision through impaired oxygen metabolism in the retina [OCT angiography (OCTA) represents a new, noninvasive visualization technique that provides vascular information on macular and peripapillary microcirculation with good repeatability and reproducibility [Therefore, the present study aimed to evaluate the changes in early superficial vessel density (SVD) and superficial perfusion density (SPD) in the macular and peripapillary regions by OCTA before and after SO removal in patients with macula-off rhegmatogenous retinal detachment (RRD). | PMC10053480 |
Materials and methods | PMC10053480 | |||
Study design and patients | viral retinitis, keratopathy, retinal atrophy, opacity, hypotony, SO tamponade, cataract, PD, retinal redetachment, glaucoma | DIABETIC RETINOPATHY, CHRONIC UVEITIS, KERATOPATHY, RETINAL ATROPHY, OPACITY, RETINAL TEAR, RETINA, CATARACT, MAY, SECONDARY, HIGH MYOPIA, LENS, RETINAL DETACHMENT, GLAUCOMA, GIANT, MACULAR EDEMA, EYE | This single-center case series prospectively included consecutive patients who underwent SO removal from June to December 2019 at Chongqing Aier Eye Hospital. Patients who underwent SO removal combined with phacoemulsification and intraocular lens implantation were included. The inclusion criteria were (1) intravitreal SO tamponade in one eye for primary macula-off rhegmatogenous retinal detachment and normal macular morphology of the attached retina, (2) PVR grade A or B, (3) macular involvement, (4) hole size < 2 PD, (5) best-corrected visual acuity (BCVA) in the eye administered SO tamponade > 0.1 using the international standard visual acuity chart, (6) no SO emulsification, (7) clear media in both eyes, (8) without hypotony, (9) without viral retinitis, and (10) without chronic uveitis. The exclusion criteria were: (1) keratopathy, severe cataract, or diabetic retinopathy, (2) macular edema or hole, (3) giant retinal tear, (4) high myopia or retinal atrophy caused by high myopia, (5) glaucoma, (6) secondary epiretinal membrane (ERM), (7) retinal redetachment during follow-up, (8) optical media opacity overtly interfering with OCT imaging, or (9) pediatric retinal detachment. Patients with suspected drug toxic side effects were not excluded because the causality could not be determined with certainty. Eyes with SO tamponade that met the above criteria were selected as the SO tamponade eye group. Contralateral eyes with BCVA (LogMAR) < 0.1 and OCTA signal strength above 8 were selected as control eyes.When the current study was first designed, there was no perfluoropropane (CThe study was performed according to the Declaration of Helsinki. It was approved by the Ethics Committee of Chongqing Aier Eye Hospital (EC approval number: IRB2019009). All participants provided signed informed consent. Clinical trial registration: Registration date: May 22, 2019; Registration number, ChiCTR1900023322; Registration site, Chinese Clinical Trial Registry (ChiCTR). | PMC10053480 |
Surgical procedures | cataract | CATARACT, LENS | SO removal was performed under retrobulbar anesthesia by associate chief physicians (L.L. and G.W.) using the 23-G Constellation device (Alcon, Fort Worth, TX, USA) and trocars in the inferotemporal and superior quadrants 3.5 mm from the limbus. Infusion liquid was used for oil exchange. An infusion line was inserted into the inferotemporal port, and all the SO was removed using a supratemporal approach with the vacuum set at 450–600 mmHg. Phacoemulsification and intraocular lens implantation through a 2.75-mm micro-coaxial incision were performed when needed (n = 3 patients in the SO group). SO removal was carried out by the pars plana approach upon confirmation of retinal attachment. Following silicone oil removal, the trocars were removed, and the sclerotomies were closed with an 8 − 0 vicryl suture. After SO removal, the patients did not need to follow any position.Among the 50 patients treated with high-density SO (5000 centistokes, Carl-Zeiss, Germany), three also underwent cataract surgery; none of the patients administered C | PMC10053480 |
Examinations | cataract, retinal detachment, SO tamponade | CATARACT, RETINAL DETACHMENT, INTRAOCULAR PRESSURE | The diagnosis of retinal detachment was initially confirmed by slit lamp biomicroscopy and indirect ophthalmoscopy. Perioperative data were obtained from the medical records, including age, sex, axial length, and duration of SO tamponade. BCVA (LogMAR) and intraocular pressure (IOP) in every patient were measured daily during hospitalization. The Lens Opacities Classification III System (LOCS III system) was used to specify cataract classification. | PMC10053480 |
Assessment of visual acuity | The BCVA assessment was performed using an international standard visual acuity chart, and data were transformed into the logarithm of the minimum angle of resolution (LogMAR) units. | PMC10053480 | ||
OCTA and analysis | SPD, tamponade | In this study, 6 × 6 mm
OCT angiography (OCTA) in a 50-year-old male with an eye administered silicone oil (SO) tamponade. The central area (1-mm diameter central circle), the mean and sector values of the inner ring between the 1-mm and 3-mm diameter circles, the outer ring between the 3-mm and 6-mm diameter circles, and the full area (6-mm diameter outer circles) were assessed. Superficial vessel density (SVD) of the macular and peripapillary regions (A and C) and superficial perfusion density (SPD) of the macular and peripapillary regions (B and D) were automatically determined | PMC10053480 | |
Statistical analysis | Data are shown as means ± standard deviation (SD). Data analysis was performed With SPSS 23.0 (SPSS, USA). One-way analysis of variance (ANOVA) followed by the Bonferroni post hoc test was performed to analyze the differences among multiple independent samples. SVD, SPD and BCVA before and 1 day, 7 days, 1 month, and 3 months after SO removal were compared using repeated measures analysis of variance. Correlations between BCVA and SVD or SPD were assessed using Pearson’s correlation test. | PMC10053480 | ||
Results | PMC10053480 | |||
Characteristics of the patients | vitreous hemorrhage | RETINA, VITREOUS HEMORRHAGE, MACULAR HOLE, MACULAR EDEMA, INTRAOCULAR PRESSURE | Ninety-four patients were enrolled initially, among whom 54 SOT contralateral eyes with BCVA (LogMAR) < 0.1 and OCTA signal strength > 8 were selected as control eyes. Among the treated eyes, 44 were excluded due to loss to follow-up (n = 21), scans with signal strength < 6 in OCTA (n = 13), ERM (n = 3), macular edema (n = 4), macular hole (n = 1), vitreous hemorrhage (n = 1), and retina redetachment (n = 1). Therefore, 50 eyes from 50 patients (27 males and 23 females; 53.6 ± 10.9 years of age) successfully treated by SO removal between June 2019 and December 2019 were assessed. The participants’ demographic features and preoperative information are shown in Table
Demographic and presurgical features of the patients with SOTBCVA, LogMARBCVA (Snellen)0.69 ± 0.2920/79 ± 20/1100.05 ± 0.06720/22 ± 20/1500.434 ± 0.34720/44 ± 20/800.026 ± 0.04520/21 ± 20/250< 0.001< 0.001Data are shown as means ± SD unless otherwise stated. Pre-op, preoperative; BCVA, best-corrected visual acuity; logMAR, the logarithm of the minimum angle of resolution; SOT, silicone oil tamponade; IOP, intraocular pressure; SOR, silicone oil removal | PMC10053480 |
OCTA parameters of the macular region before SO removal | SO tamponade | Compared with the SOT contralateral eyes, eyes with SO tamponade showed reduced SVD and SPD in the macular region (all | PMC10053480 | |
OCTA parameters of the peripapillary region before SO removal | SO tamponade | The SVD and SPD in the central area of the peripapillary region in the eyes with SO tamponade and SOT contralateral eyes were not significantly different ( | PMC10053480 | |
OCTA parameters of the macular region of eyes administered SO tamponade and SO removal | After SO removal, both SVD and SPD in the central area, inner ring, outer ring, and full area of the macular region showed significant improvements compared with the preoperative values (repeated measures analysis of variance,
Line charts illustrating SVD and SPD in the macular region before and after SO removal. (A) SVD in the central area, inner ring, outer ring and full area of the macular region. (B) SPD in the central area, inner ring, outer ring and full area of the macular region | PMC10053480 | ||
OCTA parameters of the peripapillary region of eyes administered SO tamponade and SO removal | There were significant differences in SVD and SPD in the peripapillary region among the groups (pre-operation and postoperative 1 day, 7 days, 1 month, and 3 months), as shown in Supplementary Table | PMC10053480 | ||
Visual acuity of eyes administered SO tamponade | SO tamponade | The average BCVA (LogMAR) was higher during SO tamponade (0.69 ± 0.27) compared with the SOT contralateral control eyes (0.05 ± 0.07,
Line chart illustrating BCVA (LogMAR) before and after SO removal. BCVA (LogMAR) showed a trend of time-dependent decrease from postoperative 1 day to 3 months ( | PMC10053480 | |
Pearson correlation analysis of BCVA (LogMAR), SVD, and SPD | SPD | In the eyes with SO removal, BCVA (LogMAR) was significantly correlated with SVD and SPD in the central area, inner ring, outer ring, and full area of the macular region. The Pearson correlation test showed that SVD and SPD in the central area, inner ring, outer ring, and full area of the macular region were negatively correlated with BCVA (LogMAR) from pre-operation to 3 postoperative months (all
Correlation analysis of BCVA (LogMAR), SVD and SPD in the central area, inner ring, outer ring, and full area of the macular region from pre-operation to 3 postoperative months. (A) BCVA and SVD in the central area of the macular region. (B) BCVA and SPD in the central area. (C) BCVA and SVD in the inner ring. (D) BCVA and SPD in the inner ring. (E) BCVA and SVD in the outer ring. (F) BCVA and SPD in the outer ring. (G) BCVA and SVD in the full area. (H) BCVA and SPD in the full area | PMC10053480 | |
Discussion | neuronal damage, might damage retinal structures, ischemia, SO tamponade, avascular | ISCHEMIA, STILL, RETINA | The SVD and SPD in the central area, inner ring, outer ring, and full area were lower in the eyes with SO tamponade compared with the control eyes. It is unclear whether the decrease in macular microcirculation was due to RRD damage or SO tamponade duration. Agarwal et al. [The present study showed that SO might have a negative long-term effect on retinal microcirculation, as suggested by Kubicka-Trzaska et al. [Our results also showed no significant differences in SVD and SPD of the macular and peripapillary regions between the SOT contralateral and PPV + CIt should be noted that the exact mechanism underlying the increased macular capillary VDs observed after SO removal was not determined. OCTA utilizes optical measurements, and the waterproofing effect of SO seemed to have little impact on the current data. Still, it is worth further discussing this issue with expert physicists. SO filling and removal could affect OCTA data in multiple ways. Firstly, SO exerts pressure on the retina in the sitting, lateral, and prone positions. The pressure of SO on the fovea in the prone position might damage retinal structures and cause ischemia and neuronal damage [The present study had limitations. First, DCP and choriocapillaris were not assessed in the macular and peripapillary regions. Further investigation based on swept-source- and projection-resolved OCTA is required to confirm the current findings. In addition, other diagnostic parameters, including retinal thickness, foveal avascular zone (FAZ) area, contrast sensitivity, retinal sensitivity, and ETDRS letter scores, could be included in future studies to analyze the associations among various parameters. Furthermore, the present OCTA study only analyzed 6 × 6-mm | PMC10053480 |
Conclusion | SO tamponade, tamponade | RETINA | This research indicated that SVD and SPD were lower in eyes with SO tamponade than in contralateral eyes. SVD and SPD were increased in the macular region of the eyes with SO tamponade and removal. BCVA (LogMAR) decreased while SVD and SPD increased in the macular region after SO removal; BCVA (LogMAR) was negatively correlated with macular SVD and SPD values, suggesting an improvement in visual acuity after SO removal. Gas tamponade may not significantly affect early vascular changes, but more data are needed to support this notion. Future studies are warranted to explore the mechanism underlying retina microcirculation changes in eyes administered SO tamponade. | PMC10053480 |
Acknowledgements | The authors acknowledge all patients who participated in this study, as well as all individuals who helped perform examinations but are not listed as authors. | PMC10053480 | ||
Authors’ contributions | Conceptualization, YN H and Y W; Methodology, YN H and L L; Formal analysis and investigation, L L and G W; Writing - original draft preparation, YN H and JW X; Writing - review and editing, Y W and G W; Funding acquisition, Y W; Resources, YN H and Y W; Supervision, Y W. | PMC10053480 | ||
Funding | EYE | This study was funded by the Clinic Research Foundation of Aier Eye Hospital Group [grant number AF2018007]. | PMC10053480 | |
Data availability | All data relevant to the study are included in the article. | PMC10053480 | ||
Declarations | PMC10053480 | |||
Ethics approval and consent to participate | EYE | All procedures were performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. This study was approved by the Ethics Committee of Chongqing Aier Eye Hospital (EC approval number: IRB2019009). All participants provided signed informed consent. All methods were carried out in accordance with relevant guidelines and regulations. | PMC10053480 | |
Consent for publication | Not applicable. | PMC10053480 | ||
Competing interests | The authors have no conflicts of interest to declare that are relevant to the content of this article. | PMC10053480 | ||
References | PMC10053480 | |||
Keywords | Based on the premise that physical activity/exercise impacts hippocampal structure and function, we investigated if hippocampal metabolites for neuronal viability and cell membrane density (i.e., N-acetyl aspartate (NAA), choline (Cho), creatine (Cr)) were higher in older adults performing supervised exercise compared to following national physical activity guidelines. Sixty-three participants (75.3 ± 1.9 years after 3 years of intervention) recruited from the Generation 100 study (NCT01666340_date:08.16.2012) were randomized into a supervised exercise group (SEG) performing twice weekly moderate- to high-intensity training, and a control group (CG) following national physical activity guidelines of ≥ 30-min moderate physical activity ≥ 5 days/week. Hippocampal body and head volumes and NAA, Cho, and Cr levels were acquired at 3T with magnetic resonance imaging and spectroscopic imaging. Sociodemographic data, peak oxygen uptake (VOOpen access funding provided by NTNU Norwegian University of Science and Technology (incl St. Olavs Hospital - Trondheim University Hospital) | PMC10400748 | ||
Introduction | dementia | MRS, CORTEX | Physical activity and/or exercising are suggested as avenues to preserve brain function and structure in older adults and even to stave off dementia [Investigations into the molecular characteristics of the hippocampus might provide new insight into mechanisms through which physical activity and/or exercise impact both brain structure and function. While structural MRI of the hippocampus is widespread and well known, the measurement of cerebral metabolite levels NAA/Cr or Cho/Cr levels are hence considered biomarkers of neuronal health and neural cell membrane density, respectively. Even though MRSI is available on clinical scanners, this technique is seldom employed compared to structural MRI. MRSI in the hippocampus, a core region of interest in the study of the effects of exercise and physical activity on the brain, has not been performed. So far, only one observational study has investigated the effect of exercising on brain metabolite levels in cortex using single-voxel magnetic resonance spectroscopy (MRS) [The aim of this study was to assess NAA/Cr and Cho/Cr in the hippocampal head and body in older adults taking part in the Generation 100 study, a randomized clinical trial (RCT) of supervised exercise versus following national physical activity guidelines [ | PMC10400748 |
Methods | PMC10400748 | |||
Ethics | The RCT and the substudy were approved by the Regional Committee for Medical Research Ethics (REK 2012/381 B and REK 2012/849, respectively). Both studies adhered to the Helsinki Declaration and participants gave their written informed consent to both. | PMC10400748 | ||
The RCT study | MRS | Participants were from the RCT Generation 100 study (NCT01666340, ClinicalTrials.gov registry) which originally set out to evaluate the effect of 3 years of supervised exercise training versus following the national physical activity guidelines on morbidity and mortality in older adults. The MRS acquisition was planned to be an outcome after end of the intervention at 3 years. At 3 years, the study period was extended to 5 years due to lower mortality in the cohort than anticipated based on national numbers [All inhabitants of Trondheim, Norway, born between 1936 and 1942 registered in the National Population Registry (Participants were stratified by sex and cohabitation status before being randomized into a supervised exercise group performing either high-intensity interval training (HIIT) ( | PMC10400748 | |
The Generation 100 MRI study | DISORDERS | A total of 111 (55 men, 56 women) agreed to participate. Six were excluded due to MRI contraindications or previous neurosurgical disorders, leaving 105 participants (53 men, 52 women). The participants underwent a standardized structural MRI protocol [Flowchart describing inclusion of participants. Number ( | PMC10400748 | |
Interventions | Participants in the SEG were randomized to twice weekly MICT or HIIT sessions. The MICT sessions consisted of 50 min of continuous exercise at about 70% of peak heart rate corresponding to a rating of perceived exertion of about 13 on the Borg scale [ | PMC10400748 | ||
Sociodemographic, health, fitness, and exercise variables | Date of birth, sex, and level of education (primary school, high school, and university) were obtained at baseline [Clinical measurements, including body mass index (BMI), blood pressure, and resting heart rate, were acquired at baseline and after 3 years of intervention using standard practices [Cardiorespiratory fitness was assessed objectively as VOA physical activity questionnaire including questions on frequency and duration of exercise was used to calculate weekly exercise duration (min/WK) at 3 years (for details, see [ | PMC10400748 | ||
Brain MRI and MRSI | MRI/MRSI data were acquired on 3T Magnetom Skyra scanner (Siemens AG, Erlangen, Germany) equipped with a 32-channel head coil for homogenous signal-to-noise ratio (SNR) due to radio frequency (RF or BMagnetic resonance spectroscopic imaging (MRSI) acquisition and representative spectra. | PMC10400748 | ||
Statistics | MRS | Mean, standard deviation (SD), 95% confidence intervals (CI), and % were used as appropriate to display the distribution of variables. Statistical comparisons of sociodemographic, health, fitness, and exercise variables were performed with Group differences in NAA/Cr and Cho/Cr in the hippocampal head and body were assessed in general linear models including the covariates sex, age, education, and volume of the hippocampal head or body, respectively.Since increasing VOTo investigate potential associations between variables related to exercising at time of MRS, we assessed the relationships between NAA/Cr and Cho/Cr and weekly exercise duration and intensity across all subjects in general linear models including sex, age, education, and volume of the hippocampal head or body as covariates.Finally, we investigated if HADS and MoCa scores were associated with NAA/Cr or Cho/Cr in the body or head of the hippocampus across all subjects (SEG&CG) using one general linear model for NAA/Cr and one for Cho/Cr with sex, age, education, and hippocampal volume at 3 years, to evaluate the potential clinical impact of these MRSI biomarkers.Based on the group sizes in the only previously published exercise and brain metabolite study, SPSS (IBM Corp. Released 2010. IBM SPSS Statistics for Windows, Version 28.0. Armonk, NY: IBM Corp) was used for all analyses. The statistical significance threshold was set to | PMC10400748 | |
Results | Usable spectral data were obtained in 63 (32 SEG/31 CG) of the 79 participants in whom MRSI scans were conducted. Motion, small hippocampal volumes, and technical processing/analysis issues were reasons for lack and exclusion of MRSI data. There were no significant differences in sociodemographic variables or VOSociodemographic variables and VOContinuous measures are presented as mean with standard deviation in parentheses. Categorical data is reported as percentages. Significance threshold was set to | PMC10400748 | ||
Sociodemographic, health and fitness, and exercise variables | An overview of the sociodemographic and health characteristics of the included participants in the two groups at baseline and after 3 years is presented in Table Sociodemographic and clinical variables for the supervised exercise (SEG) and control groups (CG) at inclusion and after 3 years of interventionThe continuous measures are shown as mean and standard deviation in the parentheses. Categorical data is reported as percentages. Significant threshold was set to Both CG and SEG adhered similarly well to their respective regimes, with an adherence of 87.5% and 84.4%, respectively, at 3 years (Table Adherence, exercise intensity, and duration for the supervised exercise (SEG) and control group (CG) at 3 yearsAdherence and exercised per HIIT protocol are reported in percentages, while exercise intensity and duration as mean with standard deviation in parenthesis. | PMC10400748 | ||
Hippocampal metabolite ratios, intervention groups, VO | The observed mean, SD, 95% CI, and Cohen’s Mean, standard deviation (SD), and 95% confidence interval for the raw observations of NAA/Cr and Cho/Cr ratios in the hippocampal body and head in the control group (CG) and supervised exercise group (SEG)CGThe general linear model revealed a significant effect of group on NAA/Cr ratio in the hippocampal body with lower levels in SEG compared to CG after controlling for age, sex, education, and hippocampal body volume. No significant group effect was uncovered for Cho/Cr in hippocampal body or for NAA/Cr or Cho/Cr in the hippocampal head (Table Effect of intervention group on and associations of exercise measures with NAA/Cr and Cho/Cr levels in the hippocampal body and head as outcome variables#Group effect, control group > supervised exercise group, decreasing VOThere were no associations between change in VOAcross all participants (SEG&CG), weekly exercise duration was not associated with NAA/Cr or Cho/Cr in neither the hippocampal head nor body, correcting for age, sex, education, and hippocampal head or body volume. Higher exercise intensity at 3 years was associated with lower Cho/Cr level in the hippocampal body correcting for age, sex, education, and hippocampal body volume. No other associations were present for exercise intensity (Table | PMC10400748 | ||
Hippocampal metabolite ratios and associations with HADS and MoCA scores | A significant negative association was present between HADS score and NAA/Cr in the hippocampal body but not hippocampal head, with lower NAA/Cr associated with poorer psychological health (Fig. Scatter plot of rawHADS and MoCA scores versus raw NAA/Cr level in the hippocampal body and headGeneral linear model results with MoCA and HADS scores as outcomes and NAA/Cr in the hippocampal body and head, or Cho/Cr levels in the hippocampal body and head as predictorsGeneral linear models with MoCA or HADS as outcomes variable across all participants (SEG&CG). NAA/Cr or Cho/Cr from MRSI voxels in the hippocampal head and body were included as predictors in the same model corrected for sex, age, education, and right hippocampal volume. Performance on MoCA was associated with NAA/Cr in the hippocampal body but not in the head, with a lower level of NAA/Cr linked to slightly higher scores, correcting for age, sex, education, and hippocampal volume in the same model (Fig. | PMC10400748 | ||
Discussion | hippocampal head volume, dementia | STILL | This is the first exercise RCT in older adults examining metabolites in the hippocampus, a region considered highly modifiable by training and physical activity and a key structure in dementia. Opposed to our predictions, the CG had a higher NAA/Cr in the hippocampal body than the SEG after 3 years of intervention. Likewise, neither change in VOThe CG and SEG were well-matched at baseline, and both trained according to their specification with the SEG exercising at a higher intensity as intended. Still, the CG had a significantly higher level of NAA/Cr in the hippocampal body compared to the SEG. NAA/Cr is considered a marker of neuronal viability as it is located to neuronal mitochondria which are enriched in the synapses [There was no relationship between change in VOAll significant findings related to effects of exercising on hippocampal metabolites were uncovered in the hippocampal body only, but not its head. The hippocampal head volume has previously been suggested as linked to higher levels of cardiorespiratory fitness [Higher psychological distress, as measured with HADS, was associated with lower NAA/Cr in the hippocampal body across both groups. As can be seen in Fig. The lower NAA/Cr level uncovered in the SEG group could have cognitive implications [Medial temporal lobe NAA/Cr has been suggested as a potential marker of dementia [ | PMC10400748 |
Strengths and Limitations | RECRUITMENT, STILL | The main strength was the study design with recruitment from the general population into an RCT, the detailed clinical assessment from baseline, objective VOAll statistical models were corrected for variables known to be connected to hippocampal size such as age [A limitation of the study was the low number of participants in whom we were able to obtain acceptable MRSI data. Still, the final number was similar to the The lack of longitudinal MRSI data is a shortcoming of this study. It is possible differences existed in hippocampal metabolites between groups already at baseline, but given the lack of SEG and CG differences on other variables, this is likely not to be a serious problem. The results at the 3-year timepoint would have been even stronger if repeated at 5 years. | PMC10400748 | |
Acknowledgements | RECRUITMENT | The authors thank all the participants for taking part in this study, and Torill E. Sjøbakk for help with the recruitment. We thank Hanne Nikkels, Stine Bjøralt, and the radiographers at the 3T scanner for help with the MRI/MRSI data collection. We also thank those involved with the clinical testing, including VO | PMC10400748 | |
Author contribution | Line Skarsem Reitlo contributed to the data quality control, statistical analysis, figures, drafting, and revision of the manuscript. Jelena Mihailovic performed the MRSI data analyses, wrote methods, and revised the manuscript. Dorthe Stensvold and Ulrik Wisløff supervised the RCT Generation 100 study; were responsible for exercise, health, and clinical data collection; and revised the manuscript. Fahmeed Hyder supervised MRSI analyses and revised the manuscript. Asta Håberg supervised the MRI substudy in Generation 100, organized the data collection, collected data, performed statistical analysis, and drafted and revised the manuscript. | PMC10400748 | ||
Funding | Open access funding provided by NTNU Norwegian University of Science and Technology (incl St. Olavs Hospital - Trondheim University Hospital) The Generation 100 study was supported by the Research Council of Norway; The K.G. Jebsen Foundation for medical research, Norway; Norwegian University of Science and Technology (NTNU); Central Norway Regional Health Authority; St. Olavs Hospital, Trondheim, Norway; and the National Association for Public Health, Norway. The brain MR acquisition was supported by Norwegian Advisory Unit for fMRI, Department of Radiology and Nuclear Medicine, St. Olavs Hospital, Trondheim. | PMC10400748 | ||
Data Availability | Data used in this manuscript can be accessed by contacting the corresponding author. Access to data by qualified investigators will be subject to ethical and scientific review (to ensure the data is being requested for valid scientific research) and must comply with the European Union General Data Protection Regulations (GDPR), Norwegian laws and regulations, and NTNU regulations. The completion of a material transfer agreement (MTA) signed by an institutional official will be required. | PMC10400748 | ||
Declarations | PMC10400748 | |||
Conflict of interest | The authors declare no competing interests. | PMC10400748 | ||
References | PMC10400748 | |||
Abstract | PMC10417045 | |||
Introduction | NSCLC | LUNG CANCER, NSCLC | Cisplatin plus pemetrexed followed by pemetrexed is an efficacious platinum combination regimen for advanced non‐squamous, non‐small cell lung cancer (NSCLC). Data regarding the addition of bevacizumab, especially in maintenance treatment, are insufficient. | PMC10417045 |
Methods | NSCLC | NSCLC | Eligibility criteria included: no prior chemotherapy; advanced, non‐squamous, NSCLC; performance status ≤1; and epidermal growth factor receptor mutation‐negative. Patients ( | PMC10417045 |
Results | Thirty‐five patients each were randomized to the pemetrexed/bevacizumab group and the pemetrexed alone group. PFS was significantly better in the pemetrexed/bevacizumab group than in the pemetrexed alone group (7.0 vs. 5.4 months, hazard ratio: 0.56 [0.34–0.93], log‐rank | PMC10417045 | ||
Conclusions | NSCLC | NSCLC | Addition of bevacizumab to pemetrexed as maintenance therapy prolonged PFS in patients with untreated, advanced, non‐squamous NSCLC. Furthermore, an early response to induction therapy and pretreatment M‐MDSC counts may be related to the survival benefit of the addition of bevacizumab to the combination of cisplatin and pemetrexed.
| PMC10417045 |
INTRODUCTION | NSCLC, death, non‐squamous cell lung cancer, (PD‐1)/programmed cell death, Non‐small cell lung cancer, PD‐L1 | LUNG CANCERS, NSCLC | Non‐small cell lung cancer (NSCLC) has been one of the most common causes of cancer‐related death.NSCLC accounts for 80%–90% of all lung cancers, and non‐squamous cell lung cancer accounts for 70%–80% of all NSCLC cases.Bevacizumab is a monoclonal antibody that targets vascular endothelial growth factor (VEGF).Recently, immune checkpoint‐inhibitors targeting the programmed cell death 1 (PD‐1)/programmed cell death ligand 1 (PD‐L1) have been shown to improve survival in advanced NSCLC.Thus, a randomized, Phase II study comparing maintenance therapies of pemetrexed plus bevacizumab versus pemetrexed alone after treatment with cisplatin, pemetrexed, and bevacizumab was conducted. The main objectives of the study were to determine the efficacy of the addition of bevacizumab in maintenance therapy for previously untreated advanced non‐squamous NSCLC. This randomized, Phase II study was reported in accordance with the CONSORT (Consolidated Standards of Reporting Trials) Statement. In addition, this study was conceived and initiated before the widespread use of immune checkpoint inhibitors as part of first‐line treatment. The numbers of immunocompetent cells in peripheral blood were analyzed in some patients. | PMC10417045 |
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