Acute ischemic stroke (AIS) is a most prevalent cause of serious long-term disability worldwide. Accurate prediction of stroke prognosis is highly valuable for effective intervention and treatment. As such, the present retrospective study aims to provide a reliable machine learning-based model for prognosis prediction in AIS patients. Data from AIS patients were collected retrospectively from the Second Affiliated Hospital of Xuzhou Medical University between August 2017 and July 2019. Independent prognostic factors were identified by univariate and multivariate logistic analysis and used to develop machine learning (ML) models. The ML model performance was assessed by area under the receiver operating characteristic curve (AUC) and radar plot. Shapley Additive explanations (SHAP) values were used to interpret the importance of all features included in the predictive model. A total of 677 AIS patients were included in the present study. Poor prognosis was observed in 209 patients (30.9%). Six variables, including neuron specific enolase (NSE), homocysteine (HCY), S-100β, dysphagia, C-reactive protein (CRP), and anticoagulation were included to establish ML models. Six different ML algorithms were tested, and Random Forest model was selected as the final predictive model with the greatest AUC of 0.908. Moreover, according to SHAP results, NSE impacted the predictive model the most, followed by HCY, S-100β, dysphagia, CRP and anticoagulation. Based on the RF model, an online tool was constructed to predict the prognosis of AIS patients and assist clinicians in optimizing patient treatment. The present study revealed that NSE, HCY, CRP, S-100β, anticoagulation, and dysphagia were important factors for poor prognosis in AIS patients. ML algorithms were used to develop predictive models for predicting the prognosis of AIS patients, with the RF model presenting the optimal performance. AIS imposes a very heavy burden on high-income countries with the rapid development of social economy. Furthermore, the corresponding burden is increasing rapidly in low-income and middle-income countries3. The identification of risk factors associated with poor prognosis in AIS patients could assist clinicians to provide close surveillance and timely intervention for high-risk stroke patients with poor prognosis and may guide the implementation of strategies in organized stroke care provision, thereby optimizing clinical outcomes. Machine learning (ML) algorithms can efficiently identify features highly correlated to outcomes from a large number of features, outperforming traditional statistical methods5. Consequently, ML can be used to improve the prediction accuracy of prognosis.Acute ischemic stroke (AIS), is the fifth leading cause of death in the United States8. Therefore, the goal in this retrospective study was to identify factors associated with prognosis for patients with stroke and develop an ML-based predictive model. Moreover, the proposed model was integrated in an online tool to provide clinicians and patients with visual and practical predictive assessment.ML algorithms using big data have improved and optimized the predictive performance of the prognosis prediction, as reported by prior literature9. Exclusion criteria: (1) Incomplete clinical data. (2) Patients with severe abnormal organ function. (3) Inadequate auxiliary examinations. (4) Follow-up less than one year. The diagnosis process of AIS was completed and confirmed independently by two physicians. In situations where there was diagnostic disagreement, the final diagnosis was reviewed with a senior physician to reach a consensus. This study was approved by the Ethics Committee of the Second Affiliated Hospital of Xuzhou Medical University, and all studies were conducted in accordance with relevant guidelines/regulations and the Declaration of Helsinki, and informed consent was obtained from all participants.Retrospective data were obtained from electronic health record of the Second Affiliated Hospital of Xuzhou Medical University. Patients diagnosed with AIS from August 2017 to July 2019 were enrolled in this study cohort. Inclusion criteria were: The diagnosis of AIS met the requirements of the World Health Organization with symptom onset less than 24 h10. Clinical prognosis was assessed according to the modified Rankin Scale (mRS) according to the results of 1-year follow-up. The mRS ≥ 3 was classified as poor prognosis and mRS < 3 was classified as good prognosis. All detection indexes were completed by the Second Hospital of Xuzhou Medical University. The flowchart of data collection is shown in Fig. In the data cleaning process, the information of subjects with missing value was deleted, and normality tests were performed for the continuous numerical variables to assess the presence of outliers. Subsequently, the information of subjects with outliers was deleted. Ultimately, the current study included a total of 677 subjects in the database. The data were collected by trained and qualified members of the research group using a uniformly designed questionnaire, which included living area, occupation, education level, family economic status, eating habits , lifestyle and habits, disease medication, menstrual history  and psychosocial factors. First, the purpose and significance of the survey were explained to the patients. On the basis of patients fully understanding, informed consent forms were signed, and the patients were asked to read the guidance on the questionnaire carefully and fill it in. Patients with reading difficulties, such as illiteracy or poor eyesight, were aided by members of the research group and the contents of the questionnaire were read to them to help them fill it in. The type and severity of stroke were evaluated by clinical symptoms, head CT, MR, and angiography results. Blood lipid, blood glucose, homocysteine, and other data were obtained by laboratory tests. Blood pressure, weight, height, time of onset, and baseline National Institutes of Health Stroke Scale (NIHSS) score were also recorded. Drug use, stroke recurrence and clinical prognosis were recorded during follow-up. Dysphagia was assess by water swallowing test according to the criteriaBinary categorical features were encoded with 0 and 1; for example, the gender of patients was encoded as 0 or 1 . A total of 30 demographic and clinical variables were included as baseline variables for analysis. All parameter data were retrieved from inpatient electronic medical records. Univariate logistic analysis was performed to identify impactful clinical variables, and then statistically significant variables were included in multivariate logistic analysis.This dataset was randomly split into a training cohort (70%) and a validation cohort (30%). The training cohort was used to construct and perform cross-validated ML models to avoid overfitting, and the validation database was used to validate the predictive power of models.12.Based on the results of multivariate logistic analysis, the identified statistically significant variables were used to construct ML models. Six ML algorithms were employed to develop predictive models based on the training cohort, the performance of all candidate models was assessed using tenfold cross-validation within the training cohort, the final model was identified according to the highest mean AUC and the performance was further validated on the validation cohort. During tenfold cross-validation, the training cohort was divided into ten sets, nine of them were used for model testing and one for model assessment. Meanwhile, radar plots were drawn and the accuracy, sensitivity and specificity were calculated to evaluate performance. Due to the “black-box” nature of ML algorithms, the Shapley Additive explanations (SHAP) metric was used to interpret the models and assist doctors understand the findings of the models. The contribution of each variable to the model prediction was evaluated by SHAP valueswww.r-project.org/). Python (version 3.8) was used to develop ML predictive models and a web risk calculator.Continuous and categorical variables were expressed as mean ± SD and frequency, respectively. P-Values < 0.05 were considered statistically significant with 95% confidence intervals (CIs) applied for all analyses. Statistical analyses of the demographic and clinical characteristics of all included patients were performed in R , and all studies were conducted in accordance with relevant guidelines/regulations, informed consent was obtained from all participants, and all studies were conducted in accordance with the Declaration of Helsinki.A total of 713 AIS patients were included in this study, and 36 patients with missing value were deleted. Finally, 677 patients diagnosed as AIS were enrolled in the present study, and 209 patients had poor prognosis (30.9%). The differences between AIS patients with good and poor prognosis are described in Table A total of 474 patients were assigned to the training cohort . In the training cohort, univariable regression was used to identify fifteen significant risk factors, including Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Homocysteine (HCY), Myoglobin (MB), C-reactive protein (CRP), Neuron-Specific Enolase (NSE), S100β, treatment history , and complicates (dysphagia and stroke-associated pneumonia) Table . SubsequBased on the six significant risk factors identified through multivariable Cox regression analysis on the training cohort, the following six machine learning algorithms were used to develop predictive models: Naive Bayesian classification (NBC), extreme Gradient Boosting (XGB), Random Forest (RF), Decision Tree (DT), Gradient Boosting Machine (GBM), and Logistic Regression (LR). For internal validation, tenfold cross-validation was employed to compare the performance of all models. ROC curves were plotted, and the AUCs of all established models are illustrated in Fig. . In the final RF model, feature importance rankings of six predictors are shown in Fig. . Based on the SHAP summary plots for poor prognosis in AIS patients, the related features ranked from highest to lowest importance were NSE, HCY, S-100β, dysphagia, CRP and anticoagulation. Figure This study analyzed the independent validation set in the RF model through the SHAP package, as shown in Fig. 5https://mlmedicine-prog-prog-stroke-ysnamt.streamlitapp.com/. By entering the patient's clinical data, doctors and patients can obtain the estimated probability of poor prognosis immediately. Readers can also use these detailed parameter settings to reproduce the proposed model in Python. The model_parameter_settings.txt can be downloaded from the following publicly available GitHub repositories. (https://github.com/Wu-Shi-Nan/Acute-ischemic-stroke/blob/main/model_parameter_settings.txt).Based on the RF model, an easy-to-use online calculator was built to predict the prognosis of AIS patients, which can be obtained at 13, imposing a substantial burden on families and society in terms of disease and medical impact. Furthermore, this burden has consistently increased over the past three decades15. Consequently, there is an urgent need to research early and accurate prediction of adverse outcomes in patients with AIS, to facilitate precise clinical management and surveillance.Stroke is the second most common cause of disability and the leading cause of death among adults16. Martino et al. reported that dysphagia occurs in 37% to 78% of patients with stroke and increases the risk for pneumonia 3–11 times in patients with confirmed aspiration17. Additionally, previous literature has proved that dysphagia is the most important cause of post-stroke pneumonia20. Stroke inhibits immunological responses through the activation of the autonomic nervous system and stress axis, contributing to the development of stroke-associated pneumonia, further exacerbating the condition21.According to the present study, dysphagia was identified as a significant cause of poor prognosis in patients with stroke. Dysphagia is a common complication after a stroke22. It has been previously reported that the presence of infection during acute and subacute phases of stroke is a common predictor of a poorer prognosis23. Higher CRP values as associated with worse the infection24. Increased c-reactive protein is related to a poorer prognosis regarding the course of stroke23.The present findings showed that CRP has a negative effect on the prognosis in stroke patients. CRP is an inflammatory response indicator, which can be significantly elevated during the acute phase of an inflammatory response. Meanwhile, stroke and infection are strongly intertwined. Many studies have reported that impaired immune response occurs in stroke patients, resulting in increased susceptibility to infections25. Xie et al. showed that the interaction between the activation of coagulation and the inflammatory response leads to the consumption of coagulation factors. Additionally, patients with a higher international normalized ratio had more serious strokes, and the increased international normalized ratio was an independent predictor of one-year all-cause mortality26. Anticoagulation increases the international normalized ratio and bleeding risk, thus increasing the incidence of poor prognosis. Bautista et al. suggested that warfarin use at baseline was associated with mortality27, which is consistent with the findings of this study.Meanwhile, AIS patients are prone to develop inflammatory response, and the immune-inflammatory response is an essential process post-stroke28. Clinically, it is considered to be a serum marker of cerebral damage and hypoxia for assessing neurological prognosis29. NSE, a dimeric isoenzyme of the glycolytic enzyme enolase, is involved in the glycolytic pathway. It is abundantly present in neurons and cells of neuroendocrine origin and used as a serum marker for neuronal loss, and its highest activity is found in brain tissue cells31. S100β and NSE are markers of glial cells32. Due to stroke, ischemia and hypoxia occur in the brain, leading to rupture of the membrane structure of the neurons, and the process of acute stroke causes a large release of S100β and NSE into the blood. The degree of neurological impairment can be assessed to some extent by S100β and NSE33. Previous studies have reported that increased levels of NSE and S100B are positively correlated with poor outcomes of stroke patients36, which is consistent with our findings. NSE and S100β were also included in the presented predictive model to evaluate the prognosis of patients with stroke. Meanwhile, NSE ranked first among all predictors based on SHAP analysis. In addition, HCY was related to a poor outcome in stroke patients, and the relationship between hyperhomocysteinemia and poor outcome in stroke patients has been previously reported37. When stroke patients presented with inflammatory response, cellular injury and necrosis would occur. Furthermore, as a response to this reaction, adenosine triphosphate would be released into the extracellular space, and hydrolyzed into adenosine. Adenosine has anti-inflammatory and tissue-protective properties38. However, high HCY could reduce activities and protein content of electron transport chain components, hence lowering mitochondrial energy metabolism and decreasing adenosine triphosphate production39. Thereby, for patients with high HCY, the anti-inflammatory and tissue protection in AIS patients were worse, and the prognosis was poorer accordingly.S100β and NSE were positively associated with poor prognosis in the present findings. S-100β, a member of a family of Ca + binding proteins, is a small acidic calcium-binding protein and abundantly expressed in the nervous system, mostly in astrocytes and several neuronal populationsAn RF model was developed in this study to predict the risk of poor prognosis in AIS patients, which showed excellent performance compared with other ML models. The factors NSE, HCY, CRP, S-100β, anticoagulation, and dysphagia were identified as independent factors for poor prognosis. This study has laid a foundation for timely and accurate prediction of poor prognosis risk in order to further organize stroke care. Finally, poor prognosis rates for AIS patients can be easily obtained by entering corresponding clinical features in the developed online calculator. As shown in Fig. 43. Peng et al. leveraged a cohort of 423 patients for predicting 30-day mortality in spontaneous intracerebral hemorrhage patients42. Bacchi et al. designed models using LR, RF, DT, and artificial neural networks to predict in-hospital mortality43. Chen et al. used five ML techniques, including CatBoost, XGB, Boosting Decision Tree, RF, and AdaBoost, to investigate the 90-day poor prognosis in patients with transient ischemic attack or minor stroke. The factors associated with poor prognosis were identified, and the CatBoost model (AUC = 0.839) had the best predictive performance40. However, their study had a relatively short predictive window time. Heo et al. explored the applicability of ML algorithms to predict long-term prognosis in AIS patients. They reported that the deep neural network with an AUC of 0.888 can improve the prediction of long-term outcomes, but the predictive variables were not identified5.Previous studies have attempted to use ML algorithms to evaluate the prognosis of strokeCompared to other studies, the proposed predictive model has the following advantages. First, a comprehensive range of ML algorithms were tested, including NBC, XGB, RF, DT, GBM, and LR. This comprehensive approach allows exploration of different modeling techniques and selecting the most suitable algorithm for the specific prediction task. Second, several significant risk factors were identified through the analysis, such as NSE, HCY, CRP, S-100β, anticoagulation, and dysphagia, which are independently associated with unfavorable outcomes in AIS patients. The variables mentioned above are mostly readily available patient information, which makes this model potentially suitable for assisting clinical applications. Proper use of the model can provide valuable insights into the factors influencing prognosis and aids in clinical decision-making. Third, this study employed a relatively long prediction window, which extends the observation period and captures a broader range of patient outcomes. This reduces the impact of short-term fluctuations and random variability, enhancing the reliability and stability of the predictions. Fourth, the SHAP values were used to interpret the model, providing insights into the contribution and importance of each feature in the prediction process. This enhances the model transparency and interpretability, allowing for better understanding and trust in the results. Fifth, a web-based platform that visualizes the predictive model and provides a dynamic calculator for easy and practical usage was developed. This user-friendly interface enhances the accessibility and usability of the proposed model, making it more convenient for clinical applications. Overall, the predictive model stands out by utilizing clinical samples combined with various ML algorithms, identifying significant risk factors, employing a long prediction window, providing model interpretation, and offering a user-friendly platform. These advantages contribute to its potential clinical utility and effectiveness in predicting AIS outcomes.44. Finally, it should be noted that the NIHSS score, which stands for National Institutes of Health Stroke Scale, is a widely predictor of outcomes in AIS predictive models45. The NIHSS score upon admission was found to be a significant factor in the development of unfavorable outcomes. It is important to acknowledge that the absence of the NIHSS score data in the final predictive model might have limited its performance. A prospective multiple-center cohort could be designed to enhance the credibility of the results in the future.There are several limitations present in this study. First, this is a retrospective study, which introduces the potential for selection bias and limits the establishment of causal relationships. Second, the sample size was not large enough, which may affect the generalization ability of the findings, and the data collection was limited to a single medical center, which may restrict the external validity of the results. Despite the good predictive power of our ML model, external validation in a completely different patient cohort is unavailable. Third, it is recommended to compare the predictive model with another prognostic system, such as the Acute Stroke Registry and Analysis of Lausanne score, to provide a more comprehensive evaluation and enhance the persuasiveness of the findingsIn summary, this paper established machine learning models to predict the prognosis of acute ischemic stroke. This tool can assist clinicians and patients to predict prognoses and formulate management strategies.


The result reported significant differences in vaccination coverage between the city area and the regency area (p < 0.001). Significant differences in vaccination on working day and holiday were also found in both settings (p < 0.001). Vaccination was confirmed to be higher in the city compared to the regency and decreased on holiday compared to the working day. In conclusion, factors linked to regional status and day type must be considered as important factors for developing and accelerating vaccination programs.Vaccination is a strategy to control the COVID-19 pandemic and holds a crucial impact on global health. A better understanding of factors associated with vaccination is needed to establish a good vaccination program in a population. The purpose of this study is to analyze COVID-19 vaccination program data based on regional status and day type in the West Java Province of Indonesia and contribute to discovering other characteristics of the COVID-19 vaccination program. This study is a cross-sectional study using secondary data (N = 7922) from West Java’s COVID-19 Information and Coordination Center (PIKOBAR) from January to November 2021. Independent  The global population has been enduring the devastating consequences of the Coronavirus Disease 2019 (COVID-19) pandemic since its first case detection in Wuhan, China ,5,6,7,8.Preventive measures have been taken in response to the rapid increase of reported cases, including health protocol implementation and vaccine development ,14. VaccIt is important to understand COVID-19 vaccination and its influencing factors to attain good vaccination coverage in the population. There are several factors related to vaccination, including knowledge, acceptance, hesitancy, geographical variation, healthcare capacity, and socioeconomic factors ,21,22. SVaccination number, as of 15 November 2021, had reached more than 7 million vaccine doses administered globally, with more than 215 thousand doses administered in Indonesia. The Indonesian government was targeting 234,666,020 citizens to get vaccinated, and as of 23 December 2022, the COVID-19 Task Force reported that 203,952,641 first dose vaccines, 174,666,157 s dose vaccines, and 68,201,141 first booster dose had been administered ,12. DuriThe purpose of this study is to analyze vaccination number, vaccination coverage, and vaccination trend of COVID-19 in West Java based on regional status and day type for the period January–November 2021. An analysis of regional status will provide a better explanation of how location factors may be associated with vaccination, whereas analysis of day type will give additional knowledge about changes in vaccination patterns during a particular time or event. To the best of our knowledge, no research on COVID-19 vaccination for day type has been conducted in Indonesia. The result of this study hopefully will serve as additional data for evaluating the development of the COVID-19 vaccination program in West Java, Indonesia, and another area with similar circumstances.2 and a population of 270,203,917 as of 2020. It has 16,771 islands and 34 provinces divided into 416 regencies and 93 cities [Indonesia is one of the world’s most populous countries, with an area of 1.9 million km3 cities . GroupinThis is a cross-sectional study using secondary data from the Pusat Informasi dan Koordinasi COVID-19 Jawa Barat (PIKOBAR) as in West Java’s COVID-19 Information and Coordination Center, an e-government G2Z (Government to Citizens) application model created by West Java’s Digital Service ,30. The This study analyzed vaccination numbers, vaccination coverage, and vaccination trend in West Java. Vaccination number is a calculation of the total vaccines given to the population, vaccination coverage is the percentage of vaccination number per target population, and vaccination trend defines changes in vaccination count throughout time. The regional status and day type were taken into consideration when analyzing those variables. Regional status categorizes as city and regency, whereas day type is classified into two categories; working days (days from Monday through Saturday) and holidays .p-value < 0.05) using independent t-test with an alternative non-parametric Mann–Whitney U test was chosen to find significant differences in vaccination based on regional status and day type.The data presented included the first dose and second dose vaccination, whereas the third dose or booster dose was not presented as its number was not significant enough and the vaccine had not been broadly distributed during the time of this study. Data were visualized using Tableau software Version 2022.1 and analyzed using R statistical software Version 4.2.1. Shapiro–Wilk normality test was initially done to assess normal data distribution and statistical analysis  and second-dose vaccination (p = 0.433). The differences in the median and interval range of vaccination count may be seen but not proven statistically significant.p > 0.05), therefore, the summarized data are presented as mean and standard deviation in p < 0.001) between the two groups.Vaccination coverage data (%) are normally distributed , therefore, the non-parametric Mann–Whitney U test was used. Out of 7922 available data points, 6679 data were recorded during the working day type and 1243 data were recorded during the holiday day type .According to the data shown in Further observation was conducted to confirm differences in vaccination based on day type and regional status . The nump-value < 0.001). It is also evident that the median and maximal count are lower on holidays than on the working days. These findings apply to both vaccination doses and occur in both settings.The statistical test in West Java constitutes 18 regencies and 9 cities, and the government determines each regional status based on existing criteria . SeveralThe vaccination number of each city and regency in West Java  is in liThe result in p < 0.001) in The difference in vaccination coverage is shown to be statistically significant  to expand healthcare capacity . West Jaust 2021 . Interesust 2021 . Furtherust 2021 . Althougust 2021 . The manust 2021 . This dep-value < 0.001). A further test was also performed and included in Based on day type, the vaccination trend illustrated in Many healthcare interventions can be implemented with regards to several of the circumstances discussed above. Improving vaccine attitudes, increasing vaccine accessibility, and establishing an adaptive policy may become the options for enhancing vaccination programs. However, in addition to this, providing holiday access to vaccination is the most highlighted suggestion from this study. Increasing vaccination services is required to fix the low vaccination rate that constantly occurs during holiday days. A study from America about influenza vaccines aligned with this suggestion, as they found higher vaccination coverage in vaccination programs with weekend provision of vaccines and a train-the-trainer program . This fuGebyar Vaksin mentioned before, or other special mandate-integrated programs supported by the government to increase vaccine accessibility during the holiday. Additionally, the discussion of vaccination trend analysis in this study encourages a comprehensive intervention in vaccination programs concerning public refusal issues, the effect of a particular event, and the regulatory capacity of the government. Those strategies can also be adjusted to increase the rate of booster vaccination that has been promoted nowadays.Several factors and events have influenced COVID-19 vaccination in West Java. Based on regional status, this study found a significant difference in vaccination coverage between the city and the regency area. In addition, observation of vaccination trends discovered changes in vaccination rates during a particular time, most highlighted on every Sunday and national holiday. The difference in vaccination rate during different day types is proven statistically, confirming a lower vaccination rate on holiday days compared to working days. Considering these findings, healthcare interventions, such as improving vaccine knowledge, acceptance, and willingness, should be prioritized in regencies or rural areas to increase vaccination coverage among the regency population. This study also advocates holiday access to vaccines to expand vaccine accessibility during holiday day type. Several example strategies are providing vaccine services in a 24-h-open public facility, a massive vaccination program on weekends such as This study only provides data analysis proving the statistically significant difference in vaccination count. Due to limited data variables, demographic factors could not be analyzed, and the results can only be interpreted generally. It would be interesting to investigate the relationship between vaccination coverage and health system capacity in each area. We encourage further research to add demographic data or individual-based data to allow for a detailed interpretation. The spatial analysis also could be included in a further study analyzing the effect of health system capacity on vaccination coverage.


Objective To evaluate the impact of the coronavirus disease 2019 (COVID-19) pandemic on the care of patients with miscarriage and legal termination of pregnancy in a university hospital in Brazil.Methods A cross-sectional study of women admitted for abortion due to any cause at Hospital da Mulher Prof. Dr. J. A. Pinotti of Universidade Estadual de Campinas (UNICAMP), Brazil, between July 2017 and September 2021. Dependent variables were abortion-related complications and legal interruption of pregnancy. Independent variables were prepandemic period (until February 2020) and pandemic period (from March 2020). The Cochran-Armitage test, Chi-squared test, Mann-Whitney test, and multiple logistic regression were used for statistical analysis.Results Five-hundred sixty-one women were included, 376 during the prepandemic period and 185 in the pandemic period. Most patients during pandemic were single, without comorbidities, had unplanned pregnancy, and chose to initiate contraceptive method after hospital discharge. There was no significant tendency toward changes in the number of legal interruptions or complications. Complications were associated to failure of the contraceptive method , gestational age , and preparation of the uterine cervix with misoprostol .Conclusion There were no significant differences in duration of symptoms, transportation to the hospital, or tendency of reducing the number of legal abortions and increasing complications. The patients' profile probably reflects the impact of the pandemic on family planning. The coronavirus disease 2019 (COVID-19) pandemic has affected health services around the world, requiring prioritization of the professional team and hospitals to meet the growing demand for cases complicated by the infection. Thus, the health system was structured in such a way to care for infected patients, limiting their surgical care to emergency procedures, leaving their surgical centers available to be transformed into intensive units and saving personal protective equipment.In relation to women in abortion situations, they had greater difficulty in accessing health services, since the basic health networks restricted their care; public transport reduced its fleet; the fear and the need for home isolation left the population without adequate screening or isolated until the appearance of alarm signals, delaying their care, diagnosis, and proper management, just as hospitals reduced the number of available beds, reserving hospitalization only for more critical cases, among other various socioeconomic and political factors that have impacted our current global health condition.With this in mind, in March 2020, the American College of Surgeons (ACS) recommended delay of all nonessential invasive procedures, reinforcing, however, the importance of not delaying gynecologic emergency procedures, including ectopic pregnancy and miscarriage.The COVID-19 pandemic triggered several changes in the flow of care for women experiencing an abortion. In the context outside the institution, we supposed that the reduction in the number of consultations available in basic health units and the reduction in the availability of public transport would delay the care, diagnosis, and assistance of these women, resulting in longer time experiencing symptoms and getting to the hospital. In the internal context of the institution, we can mention a reduction in the number of spaces available for hospitalization due to the need for distance between beds, and the reduction in the availability of intensive care unit (ICU) beds could limit the access of these patients to tertiary assistance.This scenario raises the following research question: What influence did the changes in routine resulting from the COVID-19 pandemic have on the quality of care for women experiencing abortion in a university hospital? The aim of this study was to evaluate the impact of the COVID-19 pandemic on the care of patients with miscarriage and legal termination of pregnancy in a university hospital in Brazil.The multicentric network MUSA—Women in Abortion Situations—is a network created by the Latin American Center for Perinatology  to improve care for women undergoing any kind of pregnancy loss during the first half of pregnancy (spontaneous or induced ones) in Latin America and the Caribbean.The sentinel centers of the MUSA network regularly provide information on maternal morbidity in early pregnancy loss, termination methods for uterine evacuations, incidence of complications related to pregnancy termination, incidence of preoperative antibiotic use and prescription of contraception before hospital discharge. Through SIP, it is possible to carry out epidemiological monitoring and comparisons between different sentinel centers over time. Representatives from each sentinel center also hold regular online meetings to discuss the data collected, conduct scientific discussions on the topic of women's health in abortion situations, and encourage good clinical practices for safe abortion.st, 2017, to September 30th, 2021, were included. The inclusion criteria were women admitted for spontaneous pregnancy loss  and legal interruption of pregnancy due to any cause or any age group who visited our hospital. The exclusion criteria were women with bleeding during pregnancy who did not have a confirmed abortion and women with ectopic or molar pregnancies. The research ethics committee of our institute approved this study .This cross-sectional study with epidemiological surveillance data was conducted between July 2017 and September 2021. All cases from the SIP-abortion database from July 1The dependent variables evaluated were: abortion-related complications  and legal interruption of pregnancy.st, 2017, until February 29th, 2020; and pandemic period (PP): from March 1st, 2020, to September 30th, 2021.The independent variables were Pre-pandemic period (PrP): from July 1The control variables were patients' clinical and sociodemographic characteristics, such as age, education, marital status, living status, health records, number of pregnancies, number of births, number of abortions, body mass index (BMI), active smoking, illegal drug use, alcohol use, planned pregnancy, pregnancy resulting from contraceptive failure, date of admission at the hospital, if it is a medically induced abortion for legal reasons, gestational age, presence of any complications, and admission data, besides duration of transportation and symptoms.Initially, a descriptive analysis of the data was performed. For continuous variables, the mean, standard deviation, median, minimum, maximum, and quartiles were calculated. For categorical variables, the relative frequencies were calculated. To assess whether there was a change in the trend in the occurrence of the outcome variables, the Cochran-Armitage trend test was performed. To evaluate the association between abortion-related complications and the independent variables, the Chi-squared or Fisher exact tests were performed for categorical variables, and the Mann-Whitney or Kruskal-Wallis tests for continuous variables. To evaluate the factors independently associated with abortion-related complications, a multiple logistic regression was performed, with “stepwise” selection criteria for variables. The significance level assumed was 5%. The software used for the analyses was the SAS System for Windows, version 9.2. .p = 0.014). The mean body mass index (BMI) was 27.25 ± 5.90 in the PrP and 26.16 ± 6.09 in the PP (p = 0.014). The duration of symptoms was 3.59 ± 7.80 days, and the duration of transportation was 53.16 ± 125.57 minutes in the PrP, while in the PP, it was 4.30 ± 7.99 days and 33.94 ± 18.81 minutes, respectively . In the PrP, 91.96% of patients did not have comorbidities, compared with 96.74% in the PP (p = 0.031). In the PrP, 12.1% of patients declared drinking alcohol, while only 5.41% did in the PP (p = 0.013). A total of 32.71% of pregnancies were planned during the PrP, whereas 24.32% were had been planned in the PP (p = 0.042). In the PrP, most patients (42.36%) were accompanied by their partners, while in the PP, most patients (45.36%) came alone (p = 0.012). In the PrP, most patients (62.73%) chose not to initiate contraceptive methods at hospital discharge, while in the PP, 53.01% chose to initiate (p < 0.001). In the PrP, most uterine-emptying procedures involved medication plus uterine curettage (41.49%), while in the PP, 40.44% underwent manual intrauterine aspiration (p < 0.001)  .p = 0.783)  had undergone legal interruption. We did not observe a significant tendency toward an increase or decrease in the number of legal interruptions.  .p = 0.960)  had abortion-related complications. Among the complications, we found that the most frequents were: infection, with 13 cases (2.32%), and 8 cases of sepsis (1.43%); excessive bleeding, with 9 cases (1.60%), and 2 cases of hypovolemic shock (0.36%); and other complications, with 6 cases (1.07%), which include post-spinal anesthesia headache, disseminated intravascular coagulation, reapproach, and allergic reaction. We did not observe a significant tendency toward an increase or decrease in the number of complications.  .p = 0.002); no cervical preparation with misoprostol (p = 0.006); type of procedure performed for uterine evacuation, with curettage being the method with the highest number of complications (p = 0.009); maternal age, with a higher number of complications among younger patients (p = 0.031); gestational age, with more complications in more advanced pregnancies (p = 0.010); and duration of symptoms, with more complications associated with longer duration (p = 0.045)  and4.5 and4In the multiple logistic regression model, it was found that the variables significantly related to complications were: failure of the contraceptive method, with a risk 2.4 times greater ; gestational age, with an increase of 12.6% for every 1 week of gestational age ; and lack of uterine cervix preparation with misoprostol, raising 2.0 times the risk of complications  .The COVID-19 pandemic has affected health services around the world and has changed how the general population experienced their diseases and sought health assistance. In relation to women in abortion situations, we supposed that changes outside the institution could hinder assistance of these women, and changes inside the institution could limit their access to the hospital. These facts brought us to the importance of evaluating the impact of the COVID-19 pandemic on the care of patients with miscarriages and legal termination of pregnancy in a university hospital in Brazil.Although we have experienced these external changes, we did not observe great differences in the duration of symptoms and time of transportation to our hospital. We imagine that, as most primary care services were closed or turned to care for patients suspected of having COVID-19, the patients probably sought our emergency room as a first form of care, as well as assuming that access to public transport was guaranteed in our city and region of coverage. However, this is not what we expected, as facing COVID-19 pandemic changes in transportation contributed to increase health disparities, hindering access to healthcare to low-income families.Regarding demographic aspects, we found that, during the pandemic, most patients were single, without comorbidities, experiencing abortions as a result of unplanned pregnancy and chose to start contraceptive methods at hospital discharge. These findings make us reflect on how the pandemic may have impaired family planning and access to contraceptive methods. We have learned from previous public health emergencies, such as the Ebola outbreak, that the impact of an epidemic on sexual and reproductive health is not a direct consequence of the infection, but an indirect result from strained health care systems, disruptions in care and redirected resources.We observed an increasing in the number of women who were hospitalized without companions. It might be influenced by the internal restructuring of our service, since it restricted the number of companions and hospital visits during the pandemic period. However, our hospital guaranteed and prioritized the presence of companions for adolescents, victims of sexual violence, and women with important physical and emotional needs.A new tendency was also observed in our hospital. Most uterine evacuation procedures performed during the pandemic were manual vacuum aspirations (MVAs), comparing to the previous tendency of using medicine for cervix preparation and curettage. Since the implementation of the MUSA network in our hospital, it was possible to generate data to assess our trends in clinical practice patterns, and the data were necessary for analyses of the safety of abortion practices and to purpose improvements in the quality of patient care and overall health outcome. In 2020, we began an intense process to insert MVA into our care practice, training the technical team, as well as modifying the institutional protocol and making MVA a priority method of uterine evacuation for abortions up to 12 weeks of gestational age, following the recommendation of the World Health Organization (WHO) and the Federation of Gynecology and Obstetrics (FIGO).We feared that external changes in health services organization and in people behavior during the pandemic could restrict women access to our hospital, resulting in a decrease of number of legal terminations of pregnancy and an increase in abortion-related complications. However, we did not observe this tendency, corroborating the hypothesis previously mentioned that patients sought for emergency attendance after primary care and that the access to our hospital was maintained during the pandemic period. This result differs from those of national data, which showed that only 55% of the 76 hospitals in our country that provide legal abortions were operating in 2019.Our multivariate analysis showed that the variables significantly related to complications were failure of the contraceptive method, higher gestational age, and no preparation of the uterine cervix with misoprostol.It is known that women using contraceptive methods can possibly not recognize symptoms of pregnancy, resulting in late diagnosis and delay in seeking medical attention, increasing the risk of infection and/or hemorrhage.Our study showed that each week of gestational age increased 12.6% the risk of complications, while another study showed an increase in the number of complications by up to 20% in each week.Preparing the cervix prior to the procedure reduces this risk to less than 1% of cases.This study had some limitations. First, it was a cross-sectional study; thus, a cause-effect relationship could not be established. Furthermore, it was not possible to differentiate provoked abortion from spontaneous abortion, except in cases of legal induction. However, our study was important to evaluate the impact of the COVID-19 pandemic, which caused changes all over the world and could impact negatively in women's experiencing abortion.We were pleased to find that our patients apparently did not have difficulties accessing our health service, mostly because we maintained and prioritized care for women in abortion situations despite all the reorganization and limitation we have suffered internally in the context of the pandemic.Our service did not reduce its volume of abortion attendance during the COVID-19 pandemic. Significant differences in the duration of symptoms and transportation to the hospital were not observed, neither was there a tendency to reduce the number of legal abortions, or an increase in complications. Despite reorganization of hospital function due to this public health emergency, we were one of 55% of services still providing legal abortions in our country. Our patients' profiles reflect the impact of the pandemic on sexual and reproductive health. This outbreak situation showed us that, in our institution, the infection might not have directly affected how women have experienced abortion, but how the reorganization of health system impacted on family planning.


The aim of this systematic review was to present the current evidence on the clinical use of single-photon emission computed tomography/computed tomography (SPECT/CT) in the evaluation of noninfected painful knees after knee arthroplasty.Embase, PubMed, Google Scholar, Ovid, Scopus, Science Direct and the Cochrane Database of Systematic Reviews were searched from database inception to May 2022 following the PRISMA guidelines. As a primary outcome, we defined the role of SPECT/CT in the diagnostic approach to noninfected painful knee arthroplasty; as a secondary objective, we described the noninfection-related factors linked to painful knee arthroplasty. Pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio values and other indicators were calculated; receiver operating characteristic (ROC) curve analysis results and a summary of the areas under the curve (AUCs) from the included studies were reported. A Fagan plot, likelihood ratio plot and Deeks’ funnel plot were generated and analysed. Methodological quality was assessed using the QUADAS-2 tool, and the certainty of evidence was assessed by the GRADE approach.A total of 493 publications were identified, of which eight met the inclusion criteria, with a final pooled sample size of 308 patients. The pooled sensitivity and specificity of SPECT/CT in diagnosing the source of pain in painful knee prostheses were 0.86 (95% CI: 0.75–0.93) and 0.90 (95% CI: 0.79–0.96), respectively, with pooled +LR and −LR values of 8.9 (95% CI: 4.11–19.19) and 0.15 (95% CI: 0.09–0.28). The pooled diagnostic odds ratio was 57.35, and the area under the curve was 0.94. SPECT/CT highly accurately identified different sources of pain, such as loosening of the prosthetic components, patellofemoral overloading, instability, malalignment of the components and degeneration of the patellofemoral compartment. The confidence of the estimates was moderate according to the GRADE approach.With demonstrated high sensitivity and specificity, as a diagnostic tool, SPECT/CT can identify the source of pain in painful knees after knee arthroplasty, particularly in cases of loosening, patellofemoral disorders and component malalignment (level of evidence III). These findings have significant clinical repercussions, such as in changing the initial diagnosis, identifying or excluding different causes of painful knee arthroplasties, guiding subsequent treatment and positively impacting the final clinical outcome. We moderately recommend the use of SPECT/CT for identifying the source of pain after knee arthroplasty according to the GRADE assessment. This review was preregistered in Prospero under code CRD42022320457.The online version contains supplementary material available at 10.1186/s13018-023-03687-8. A painful knee after knee arthroplasty represents a major diagnostic challenge for orthopaedic surgeons. Despite a detailed history and a thorough clinical examination, it is often difficult to precisely identify the cause of the pain and establish a correct diagnosis . DiffereAssessment of the painful knee requires a multimodal approach, as the treatment depends largely on the underlying aetiology. Imaging is an established and important pillar for the clinical assessment and evaluation of the cause of knee pain.Conventional X-rays (XRs) are the first line of investigation, as they are commonly available and relatively cost-effective. Gross abnormalities, such as periprosthetic fractures, subsidence of prosthetic components or severe loosening, can be easily detected; however, the detailed assessment of anatomical structures is limited. Computed tomography (CT) is useful in the evaluation of cortical bone abnormalities, providing excellent anatomical detail but a suboptimal assessment of soft tissue abnormalities and intramedullary changes. CT also allows a detailed analysis of the position of the prosthetic component with regard to standardized references .Several studies have shown the diagnostic value of supplemental magnetic resonance imaging in the evaluation of symptomatic joint replacement , 8; howePlanar scintigraphy (bone scanning) has a high but varying sensitivity with limited specificity for several pathologies. By performing tomographic reconstruction through SPECT, it is possible to obtain images with better contrast resolution while improving the anatomical localization and characterization of the lesions . FurtherHybrid SPECT/CT, with a radiation burden of only 2–4 mSv, has emerged as an imaging tool with important advantages for diagnosing painful knees after arthroplasty: (a) it offers the anatomical detail and spatial resolution of CT while enhancing the specificity of SPECT ; (b) it Previous studies, be they evaluations of diagnostic tests or correlation studies, have demonstrated the good diagnostic performance of SPECT/CT in evaluating painful knee replacement; however, the sample sizes have been relatively small, and thus, the robustness of the evidence is questionable. Moreover, most of the current evidence is from observational cohort studies, and few studies examining diagnostic accuracy have been published. To date, published systematic reviews related to painful arthroplasty are scarce: Barnsley et al.  analysed99mTc-phosphate SPECT/CT in the evaluation of noninfected painful knee arthroplasty. A meta-analysis on quantitative methods was also conducted where possible. Under this PICO algorithm [This systematic review was conducted with the primary aim of analysing the best written evidence regarding diagnostic tests using lgorithm , “In aduTypes of study: This review included full-text reports of systematic reviews, observational studies and prospective and retrospective cohort studies, the data of which could be used for analysis purposes in the category of diagnostic studies. Studies required a sample size larger than 10 cases, which would allow the possibility of constructing a 2 × 2 table.Types of participants: Adult patients with painful knees after primary  or revision knee arthroplasty who had undergone bone SPECT/CT scintigraphy as part of their diagnostic work-up.Type of intervention: intravenous 99mTc HMDP/99mTc HDP/99mTc MDP or intraarticular 99mTc sulphur colloid, SPECT/CT.Type of study outcome: The final diagnosis was related to aseptic painful knee arthroplasty. The gold standard in the study was either the result of an intraoperative finding, histological examination, clinical outcome or a comparable standard result.Studies were excluded if the focus was on oncology or infection-related applications or if the emphasis was placed on aspects related to generators, radiochemistry, animal models, experimental reports or physics. Descriptive studies focused solely on the pattern of BTU in which the authors did not use any comparator to infer the explanation of the findings were also excluded. Small sample size studies with fewer than 10 patients were not included, as the minimum requirements for analysis in this review were not met. Reviews, case reports, conference presentations and so on were excluded. We also excluded studies for which we were unable to separate the results for knee prostheses from those for other prostheses as well as the results from different pathologies (e.g. septic from aseptic loosening).Years considered: 2010–2022.Languages considered: English, Spanish, Italian.This systematic review was conducted in adherence with the PRISMA guidelines  and the SPECT/CT, SPECT, single-photon emission computed tomography/computed tomography, knee prosthesis, knee arthroplasty and aseptic loosening were used as keywords in the literature search.The Cochrane Central Register of Controlled Trials (CENTRAL) published in the Cochrane Library and the Embase, PubMed, Google Scholar, Ovid, Scopus and Science Direct databases were all searched. The language was restricted to English, Italian and Spanish. Grey literature was searched through clinicaltrials.gov and a summary of conferences. When possible, authors were contacted for clarification. Because SPECT/CT began to be used as a hybrid imaging modality in knee arthroplasty orthopaedic practice in 2010, there was no written evidence about its use in this topic before that year; all relevant studies published from 2010 to May 2022 were identified by using Boolean operators, MeSH and keyword search terms adapted for each electronic database  and specificity (SPE).Data were extracted separately by the authors using a standardized extraction tool; the decision to include or exclude an article was made by consensus reading among LKA and NH (experts in the topic). The aforementioned search strategy was used to obtain the titles and abstracts of studies with potential relevance to the review. LKA and NH independently screened the titles, abstracts and full texts for eligibility. Care was taken to ensure that multiple studies reporting on the same patient population were excluded. Therefore, duplicate records were rechecked in another round of peer review. Reviewers resolved disagreements through discussion or, if needed, by adjudication of a third reviewer (LFR). Differences were resolved by consensus.The included studies were assessed by using the Cochrane Collaboration  and QUADCertainty of evidence assessment. The quality of the evidence or confidence in the estimates of this systematic review was assessed by using GRADE guidance [guidance , first iguidance   and clinical applicability .The data were extracted from each article and classified as true or false positives or negatives, respectively; some were directly extracted, while others were calculated from the reported results. In order to perform meta-analysis of the data, following the methodology of Vlaar et al. , an adjuStatistical analysis was performed using Stata 17MP software  to calculate individual and pooled estimates of sensitivity (SEN), specificity (SPE), the positive likelihood ratio (LRP), the negative likelihood ratio (LRN) and the diagnostic odds ratio (DOR) and its 95% confidence interval (CI). Finally, a forest map, summary receiver operating characteristic (SROC) curve, Fagan’s line diagram and likelihood ratio (LR) dot plot were generated, and the area under the SROC curve (AUC) was calculated.Q-test (P < 0.10 indicates heterogeneity among studies) and I2 test , and then a random effects model was used to combine the effect sizes. Deeks’ funnel plot was used to determine whether there was publication bias in the included studies: the closer the angle between the regression line and the vertical axis in Deeks’ funnel plot, the less likely it is that publication bias was present; when P > 0.05, publication bias was considered to be absent. The stability of the results of the diagnostic studies was tested by sensitivity analysis. When the heterogeneity was large, meta-regression analysis was used to explore the sources of heterogeneity among studies, and subgroup analysis was conducted.The presence of a threshold effect was examined by calculating the Spearman correlation coefficient between the log of sensitivity and the log of (1—specificity). Heterogeneity due to non-threshold effects was assessed by the In this review, there were identified 727 potential studies evaluating SPECT/CT in the clinical scenario of noninfected painful knee arthroplasty. After checking for duplicates, 234 papers were immediately excluded; subsequently, 493 studies were screened, 421 were excluded (including 3 studies published in different languages), and the remaining 72 studies were assessed for eligibility. After reading the full-text records, 64 studies that did not fulfil the inclusion criteria were also excluded . Ultimately, a total of 8 diagnostic studies were analysed for inclusion and quantitative synthesis, as shown in Fig. According to the Oxford Levels of Evidence tool, most of the studies were considered level III.A total of eight studies classified as diagnostic tests, with a total population of 308 patients, were analysed using the QUADAS-2 tool.The overall risk for the diagnostic test studies evaluated using the QUADAS-2 tool was medium. The most frequent source of bias was verification bias (flow and timing), as not all patients received the same reference standard test; the final diagnosis regarding the cause of pain was based on intraoperative findings and/or clinical follow-up assessing the response to treatment Figs. .Fig. 2QuAbele et al.  reportedAl-Nabhani  reportedArican  reportedBo Bao  reportedChew et al.  reportedP < 0.05). They observed that SPECT/CT changed the clinical diagnosis with impact at final diagnosis in 85% of patients. The major limitation of this study was that the results came from the use of only two TKA implant designs (cruciate-retaining and posterior cruciate ligament-stabilizing implants); it was not possible to generalize the results to other implant brands and designs.Hirschmann et al.  reported99mTc MDP bone scanning.Mandegaran et al.  obtainedMurer et al.  performeThree authors reported that SPECT/CT changed the clinical diagnosis and final treatment in 65–85% of all cases , 44, 46.99mTc sulphur colloid was used intraarticularly (SPECT/CT arthrography) [The best diagnostic performance with the highest sensitivity and negative predictive values was found for loosening of the prosthetic components when the bone radiotracer ography) , 42.Three authors reported sensitivity and specificity values separately per compartment , with the best results obtained for the tibial and patellar components , 43, 46.I2 in the Q test to determine whether there was a non-threshold effect for each combined effect size. The I2 value of SEN was 62.7|1 and that of SPE was 84.98 , the combined SPE was 0.90 (95% CI: 0.79–0.96), the combined PLR was 8.89 (95% CI: 4.11–19.19), the combined NLR was 0.15 (95% CI: 0.09–0.28)  Fig. .Fig. 10SP value was not statistically significant (P = 0.02), indicating publication bias , a conditional recommendation for the use of SPECT/CT in identifying the source of knee pain after TKA was made  and specificity of 0.90 (95% CI: 0.79–0.96) in diagnosing the source of pain in painful, noninfected knees after knee arthroplasty. With a + LR and -LR of 8.89 and 0.15, respectively, SPECT/CT has good accuracy in detecting the source of pain in painful knee arthroplasty patients. With a moderate certainty of evidence according to the GRADE assessment, it was possible to make a conditional recommendation for the SPECT/CT tool for localizing the source of pain in patients with painful knees after knee arthroplasty.There are a few studies in the literature similar to this systematic review. For example, Barnsley et al.  comparedThe present systematic review included a broader spectrum of diagnostic studies focusing only on painful, noninfected knees after knee arthroplasty. With a medium risk of bias according to the QUADAS-2 tool, this review showed high heterogeneity between the studies, similar to previous reports , 27.The LR values presented in the analysis provided support for the clinical applicability of SPECT/CT in detecting the source of pain in painful knee arthroplasty patients; SPECT/CT can clearly help clinicians make decisions regarding treatment. The SROC curve showed an AUC of 0.94 (95% CI: 0.95–0.98), confirming the good diagnostic performance of this tool.99mTc sulphur colloid with a sensitivity and negative predictive value of 100%, which was superior to other imaging methods. SPECT/CT was also able to identify other sources of pain, such as patellofemoral hyper pressure, instability and malalignment of the components, with findings confirmed by intraoperative or clinical follow-up [Three authors , 43, 46 ollow-up , 47.The majority of authors applied a systematic method by using an image scheme protocol that allowed them a) to report typical patterns of BTU for specific pathologies with high intra- and interobserver correlation and b) to use a biomechanical approach to the clinical condition.P < 0.05). Verschueren et al. [P = 0.042) and anterolateral regions (P = 0.016) of the femur. They also found that an increased blood pool at the internal tibial plateau was related to a sixfold–12-fold increase in the need for revision surgery. Rasch et al. [P < 0.005). The use of this image scheme was also important for defining particular BTU patterns associated with specific conditions, such as malpositioning of the components, maltracking, patellar overloading, patellar osteoarthritis and loosening, which led the clinician to change the initial diagnosis in up to 85% of the patients [P < 0.05) between different patterns of BTU and the position of the TKA components together with different pain patterns, enhancing the importance of the component position as a potential source of pain in painful knee arthroplasty patients. The authors concluded that component positioning-related pathologies accounted for the greatest proportion of cases, followed by patella-related problems and instability.Hirschmann et al.  presenten et al.  reportedh et al.  found a patients , 41, 46.patients , which sThe benefits of using a consistent model for systematically analysing patients with painful prostheses are as follows: the possibility of comparing and following results in clinical studies and establishing the correct diagnosis; the possibility of identifying a clinically unsuspected origin of pain, leading to better patient management; and the ability to obtain an accurate diagnosis with a significant impact on costs to health systems.SPECT/CT offers functional data about bone turnover patterns together with biomechanical information in TKA patients , helpingIn summary, current evidence supports the use of SPECT/CT for identifying the source of pain in painful knees after knee arthroplasty through the use of BTU patterns, where a negative scan is highly predictive of the absence of major complications, particularly in painful prostheses. The method provides combined structural, mechanical and functional information, showing benefits for establishing a diagnosis and providing guidance for further treatment. A number of justifications for the use of SPECT/CT in clinical practice in painful knee arthroplasty can be defined, including the degree to which this tool can impact the patient outcome; the reasonability of its costs; its non-invasive nature; the ability to perform the scan at different time points in the course of the disease; the ability to provide additional information that can change adherence or the nature of the intervention given; the potential to speed up decision-making and thus improve patient quality of life; the ability to correct the initial clinical suspicion for tibial or femoral component loosening and provide different underlying causes of persistent knee pain after TKA ; and the ability to detect component loosening that was not initially clinically suspected.There are implications in the use of SPECT/CT for clinicians and policymakers:Improved diagnostic accuracy: This hybrid image system (SPECT/CT) can improve the accuracy of diagnosis, leading to better patient outcomes and potentially reducing the need for additional imaging studies or equivocal treatments.Increased efficiency: SPECT/CT can modernize the diagnostic process, facilitating clinicians in making more accurate diagnoses in a shorter amount of time with potential cost savings and improved patient care.Enhanced treatment planning: SPECT/CT can provide valuable information for surgery planning, allowing surgeons to improve patient outcomes.For policymakers, the use of SPECT/CT in painful knee arthroplasty may have implications for resource allocation and healthcare budgeting.Because a revision surgery is not recommended in cases of unexplained pain in TKA, an optimal diagnostic algorithm becomes essential to identify all possible causes of pain. It should be based on medical history, clinical examination, microbiological work-up and detailed imaging analysis. Standardized conventional radiographs are mandatory to identify component malposition, polyethylene wear, component over- or under-sizing, overfilling or gross loosening . Only whSome limitations need to be acknowledged. First, relevant information could have been missed by restricting the search of publications to those written in English, Italian and Spanish. Likewise, the exclusion of unpublished data, ongoing studies and existing studies for which relevant data could not be obtained might have led to publication bias.Second, the p value of Deeks’ symmetry test for publication bias was 0.02, and although it could be explained by publication bias concerns, the nature of this statistical method forces us to interpret it with caution and to consider other explanations for the small-study effects and heterogeneity, such as the influence of covariates or chance. Third, there was high heterogeneity in this study, with one of the major sources of bias being the use of different comparators, diverse surgical techniques and other factors belonging to the non-threshold effect model such as type of risk of bias, route of administration of the radiotracer and the anatomical place of the evaluated prosthesis; although the meta-regression model showed significant differences in the results, it is important to recognize the impact of the of the low sample size of the series; the results should be interpreted with caution and need to be validated with future studies including larger patient samples. Fourth, it was not possible to identify sufficient publications regarding SPECT/CT as a diagnostic test, so the results reported in this review came from a limited number of patients. Fifth, for some of the reviewed series, the sample size was small, and the authors did not explicitly calculate its size or establish a conceptual hypothesis.As mentioned above, few systematic reviews related to this topic have been published, and although the results reported in this current review are similar to previous reports , it is pTo improve the strength of the current evidence, it is necessary to conduct studies with a larger number of patients with a multicentre and prospective design to be able to compare different populations and types of arthroplasty models and improve confidence in the accuracy of SPECT/CT. Improvements in device technology, such as the introduction of metallic beam artefact suppression techniques and the possibility of using new software for quantification purposes in nuclear medicine, could lead to more accurate results and could provide new standards for image evaluation; it will be necessary to conduct studies with the new standards of the novel technology.The evidence summarized in this systematic review and meta-analysis highlights the performance of SPECT/CT in diagnosing the source of pain in painful, noninfected knees after knee arthroplasty. With high heterogeneity between published studies, the best evidence available to date shows that SPECT/CT has high sensitivity and specificity in identifying the source of pain in noninfected knees after knee arthroplasty, particularly in cases of loosening, patellofemoral disorders and component malalignment. Including this imaging tool in the diagnostic flow of painful knee arthroplasty will have significant clinical repercussions: changing the initial diagnosis, identifying or excluding different causes of painful knee arthroplasties, guiding subsequent treatment and positively impacting the final clinical outcome.Additional file 1: Supplement 1 Search strategy and search strategy database.Additional file 2: Supplement 2 Forest plot meta-regression.Additional file 3: Supplement 3 GRADE score analysis.Additional file 4: Supplement 4 PRISMA checklist.Additional file 5: Supplement 5 TP, TN, FP, FN data from papers.


Only metabolites that overlapped the two different statistical approaches  were considered in the further analysis. Multivariate analysis was performed with biomarker candidate metabolites based on linear support vector machines (SVM), partial least squares discrimination analysis (PLS-DA), and random forests (RF). The model identified five biomarker candidate metabolites that were significantly and differently expressed  in CRC patients compared to healthy controls. The metabolites were succinic acid, aminoisobutyric acid, butyric acid, isoleucine, and leucine. Aminoisobutyric acid was the metabolite with the highest discriminatory potential in CRC, with an AUC equal to 0.806 (95% CI = 0.700–0.897), and was down-regulated in CRC patients. The SVM model showed the most substantial discrimination capacity for the five metabolites selected in the CRC screening, with an AUC of 0.985 (95% CI: 0.94–1).Colorectal cancer (CRC) is one of the most common and lethal diseases among all types of cancer, and metabolites play a significant role in the development of this complex disease. This study aimed to identify potential biomarkers and targets in the diagnosis and treatment of CRC using high-throughput metabolomics. Metabolite data extracted from the feces of CRC patients and healthy volunteers were normalized with the median normalization and Pareto scale for multivariate analysis. Univariate ROC analysis, the  Colorectal cancer (CRC) is the third most common cancer and second in terms of mortality among all cancers for both sexes . GeneticBiomarkers are biological indicators that can be objectively measured and used to diagnose, monitor, or predict disease risk. Atikukke et al. studied gene mutations in a cohort of early-onset biomarkers. They stated that malignancies appear to be microsatellite-stable (MSS) with a minor tumor mutation burden according to the tumor mutational burden (TMB) measure for the genomic profiling data of these patients’ initial samples. With a notable mutation frequency of PIK3R1, PDGFRA, FLT3, and KDR gene alterations, this group of individuals appears to have a different mutational landscape [p-values, was used for the selected metabolic candidates in the case of both classes. Significant differences were determined using the Wilcoxon test for continuous variables. Findings were considered significant if the p-value < 0.05. The results suggest possible correlations between the metabolism of gut microbes and the changes in the identified metabolites according to the pathophysiology of the disease [Metabolomics analysis may provide potential advantages through the discovery of a suite of non-invasive, clinically relevant biomarkers that can identify CRC . Brown e disease . Hossain disease .It has recently come to light that microbe-derived extracellular vesicles, often known as EVs, are becoming an essential new research subject in the quest to understand the relationship between the gut microbiota and human health. Different kinds of EVs are capable of being secreted by gut microbiota, including outer-membrane vesicles (OMVs), shedding vesicles, and apoptotic bodies. EVs are made up of lipids, proteins, nucleic acids, and metabolites for the most part. Their principal function is to carry active biomolecules to cells over long distances, facilitating medication delivery to specific areas or modulating host cellular responses. Although the underlying mechanisms are still not fully understood, this is their fundamental task ,12,13,14This study aimed to investigate the biomarkers of CRC and develop a predictive model that can distinguish CRC patients by applying a methodology combining bioinformatics and machine learning approaches to metabolomics data, including the profile of metabolites in EVs from CRC patients versus healthy controls without known types of “omics” due to the nature of the model. This model conducts high-performance measurements with fewer gene biomarkers, whose number is 5 compared to the 15 gene biomarkers resulting from the work of Kim et al. .www.metabolomicsworkbench.org (accessed on 11 March 2023), where the project ID is designated as PR000888. The data can be accessed directly using the project DOI: 10.21228/M8WX1N. A total of 36 patients with colorectal cancer and 40 healthy patients as controls participated in this study. The characteristics of the patients, such as their age, gender, stage, tumor location, and carcinoembryonic antigen (CEA) test results, were evaluated. Healthy controls with no known disease and routine laboratory test results were included in the study. The exclusion criteria for healthy controls included a diagnosis of bowel disease, medication for bowel disease, and a previous diagnosis of CRC. General characteristics such as age, gender, and medical history were recorded for the healthy control subjects. The patient and healthy subject exclusion criteria were postoperative colorectal cancer recurrence, chemotherapy, complications of colorectal cancer with other cancers or metabolic diseases, drug therapy, or antibiotic therapy within one month of sample collection. The Metabolomics Standards Initiative (MSI) for all the included metabolites was set as 2. The metadata of the analyzed metabolites are listed in The data used in this study are available on the NIH Joint Fund’s National Metabolomics Data Repository (NMDR) website, Metabolomics Workbench  and gas chromatography-TOFMS (GC/TOFMS).t-test, and FDRs were determined according to the Benjamini–Hochberg procedure to minimize the false positives. Fold changes (FCs) were calculated to examine the differences between the metabolites from the CRC patients and those from the healthy patients. FDR-adjusted p-values < 0.05 and FCs ≥1.5 (up-regulated) or ≤1.5 (down-regulated) were considered significant. Furthermore, we visualized the metabolites that were consistently up- or down-regulated in the CRC patients compared to the healthy controls with a Volcano plot for exploratory biomarker analysis, as depicted in t-test and the FC, as well as those of the t-test and ROC analysis, to identify reliable biomarker candidate metabolites that significantly contributed to the differentiation of the CRC and healthy patients. Therefore, we considered only metabolites overlapping the two different statistical approaches for further analysis . Multivariate analyses were performed using the ROC curve method with biomarker candidate metabolites based on linear support vector machine (SVM) [The metabolomic data were analyzed using univariate and multivariate statistical methods. The data were normalized using the median and Pareto-scaled for multivariate analysis. Significant changes in metabolite levels were tested using the ne (SVM) , partialne (SVM) , and ranne (SVM)  algorithp-value < 0.05) in the CRC patients compared to the healthy controls. Our results showed that aminoisobutyric acid and butyric acid were down-regulated in the CRC patients, while succinic acid, isoleucine, and leucine were up-regulated. When the FC values were examined, aminoisobutyric acid and butyric acid were down-regulated 0.60- and 0.18-fold in the CRC patients compared to the healthy controls. In addition, succinic acid, isoleucine, and leucine were up-regulated 2.04-, 1.63-, and 1.73-fold in the CRC patients, respectively  were identified as potential diagnostic biomarkers of CRC. The individual ROC curve analysis results are presented with the cut-off point, AUC with 95% CI, sensitivity, and specificity values that show how effectively the selected candidate biomarkers can discriminate between the two diagnostic groups . Our results showed that aminoisobutyric acid had the highest discriminative potential, with an AUC equal to 0.806 (95% CI = 0.700–0.897), and leucine had the lowest discriminatory potential, with an AUC equivalent to 0.765 (95% CI = 0.646–0.861)  . Figure In the third part of the analysis, we combined five biomarker candidates and plotted the receiver operating characteristic (ROC) curves with the 95% CI to develop biomarker models based on machine learning and statistical algorithms . A total of 10 cross-validations (CVs) were performed to generate the ROC curves, and the results were averaged to generate the plots. The SVM model with a 0.985 (95% CI: 0.94–1) AUC showed strong discrimination capacity for the five metabolites selected in the CRC screening compared to the PLS-DA, with a 0.802 (95% CI: 0.618–0.952) AUC, and the RF models, with a 0.929 (95% CI: 0.824–0.994) AUC . For eacColorectal cancer, which is a prevalent kind of cancer, is a malignant tumor. Surgery, chemotherapy, radiotherapy, targeted therapy, and other forms of treatment are currently available for patients diagnosed with colorectal cancer. However, less than 15% of patients will live for five years after being diagnosed with colorectal cancer. Approximately 40% of CRC patients will eventually relapse and develop recurrence or late metastases. To develop a personalized treatment plan, it is essential to first identify the biomarkers linked with CRC and then forecast which patients will develop the disease .This study may guide future clinical metabolomics studies aiming to search for different combinations of metabolic features with more reliable and robust diagnostic screening to differentiate CRC cases. The findings of this work agree with the results of the work conducted by Kim et al., where succinic acid, isoleucine, and leucine were up-regulated, while aminoisobutyric acid was down-regulated. However, the predictability of Kim et al.’s model was 92.0% with 15 metabolic biomarkers , compareTerasaki et al. suggested that succinic acid is a prognostic biomarker for CRC. The results strongly indicate physiological changes in human colorectal cancer stem cells (CCSCs) induced by Fucoxanthinol (FxOH) treatment. Based on metabolite profiling via GC-MS analysis, the authors reported that reduced glycine and succinic acid levels were correlated with EMT suppression and apoptosis induction in human colorectal-cancer-stem-cell (CCSC)-like spheroids  . Long etMultivariate analysis is based on multivariate statistics. Typically, it addresses situations where multiple measurements of each experimental unit are made, and the relationships between these measurements and their structures are important. It is complicated by the problem’s dimensionality, where the number of features is very high compared to the number of samples. However, it is a powerful technique that can be used to search for the best feature subset that can represent the entire dataset with a high prediction performance . The linInterestingly, the selected genes were both able to predict the two classes with AUC ranges from 0.765 to 0.806, as seen in The succinate dehydrogenase gene (SDH) is a gene associated with the production of succinic acid. Dysfunctions in succinate dehydrogenase (SDH) metabolic enzyme activity lead to an abnormal accumulation of succinic acid. SDHD is a subunit of the SDH gene that was found to be down-regulated in 308 colorectal cancer samples compared to 41 normal samples, as seen in In their mini-review, Zhang et al. reported that metabolites have a largely untapped potential for the diagnosis of CRC and oncology through the study of the cancer metabolome to identify metabolite biomarkers defined as surrogate indicators of physiological or pathophysiological states . The resThis study explored a model that applies statistical and machine learning methods that extract metabolic biomarkers for CRC. The results suggest that five metabolites may serve as strong predictors of the disease, which may assist in diagnosis, progression, and treatment based on the measurement of these metabolites in the body. The metabolite biomarkers were extracted from the patients’ stools, which is a less invasive approach than tissue biopsy that leads to less pain and side effects. The findings were in agreement with Kim et al.’s  work usiThe proposed machine learning model is based on multivariate feature analysis that selected five metabolites and incorporated them in an MCCV cross-validation to test three standard classifiers: linear SVM, PLS-DA, and RF. Linear SVM outperformed the other two by correctly classifying 35 of 36 samples from CRC patients and 39 of 40 healthy control samples with an accuracy of 97%.The nature of this proposed machine learning model allows it to be used in other “omics” and for different health outcomes, including cancers and other complex diseases. The model may be used to integrate multi-omics data in order to better understand the disease progression. A future direction could be to study how the results of the model can be used in clinical practice, and wet-lab experiments could be conducted to validate the relationship between the extracted metabolites levels and the advancement of CRC cells. Integration of the findings with other omics and clinical data may help to explain how these omics work in the cell. Young sporadic CRC has been increasing in North America  in recen


Crohn’s disease (CD) is a subtype of inflammatory bowel disease (IBD). CD is a health problem in Western countries such as the US and European nations and is an idiopathic disease; however, certain cases of CD have been associated with intestinal dysbiosis. A systematic review with a meta-analysis was carried out to determine the efficacy of a diet rich in fiber with or without cointervention to improve remission rates for CD. The literature in the PubMed, Scopus, Web of Science, and ClinicalTrials databases was reviewed. The quality of the studies was evaluated using the Johanna Briggs Institute (JBI) scale. This review was conducted in accordance with the structure outlined in the PRISMA statement. In addition, a meta-analysis was performed with a 95% confidence interval (CI) and a random effects model. Eleven studies were included, totaling 2389 patients with CD. Applying a diet rich in fiber with or without the administration of routine therapies improved CD remission rates. Data regarding CD activity, remission time, and adverse effects derived from fiber consumption were analyzed. Consumption of fiber in the diet could improve remission rates for CD patients who receive or do not receive other treatment to maintain remission. Inflammatory bowel diseases (IBDs) are idiopathic pathologies, among which there are three subtypes: Crohn’s disease (CD), ulcerative colitis (UC), and unclassified IBD (IBD-U), the latter being the least frequent, accounting for 4% of IBD cases in Western countries . SpecifiIn patients with IBD, quality of life is highly compromised compared with that in individuals who do not suffer from gastrointestinal diseases . The sigDespite being a set of idiopathic diseases, several factors that promote the appearance of IBDs have been detected, including the following examples: (1) genetic factors ; (2) environmental factors related to developed countries ; and (3) immune system issues, which include decreased intestinal mucus, the infiltration of T and B lymphocytes, and the overproduction of inflammatory mediators such as TNFα, IFNγ, IL-1β, and IL-23, which in turn lead to abnormalities in the action of white cells such as macrophages, neutrophils, and NK T lymphocytes .Faecalibacterium prausnitzii (F. prausnitzii), Clostridium leptum (C. leptum), and Bacteroides have anti-inflammatory capacities at the intestinal level through the production of short-chain fatty acids (SCFAs), and these species are diminished in patients with IBDs [E. coli and Fusobacterium are more abundant [Another factor to consider in order to understand the pathogenesis of IBDs is the intestinal microbiota. Specifically, compared with individuals without IBD, those with IBD have imbalances in different commensal species at the intestinal level; this phenomenon is known as dysbiosis . In geneith IBDs . In contabundant .SCFAs are anti-inflammatory substances that are produced by the degradation of soluble fiber at the intestinal level by the aforementioned microbiota species . Some exAmong IBDs, CD is the most common. To control the symptoms of CD, there are multiple therapeutic options, of which those whose objective is to regulate intestinal inflammation by directly affecting the functioning of the immune system stand out . There aTo date, how the consumption of foods rich in fiber can exert beneficial effects on individuals with CD has been studied on other occasions; for example, a Cochrane review carried out in 2019 included 18 studies on dietary interventions for CD. However, not all the studies included in the review analyzed fiber consumption ,22.The objective of this study was to synthesize the scientific evidence available to date of a diet rich in fiber as a method to prevent acute flare-ups of CD as well as to analyze the effects regarding positive clinical improvements.This systematic review was carried out in accordance with the standards outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement . The detThe following databases were searched: PubMed, Scopus, Web of Science, and ClinicalTrials.The searches were conducted to answer the research question directly, which was developed in the population, intervention, comparison, and outcome (PICO) format . The seaComponents of the PICO research question are as follows: P: problem; I: intervention to be analyzed; C: comparison or control; and O: outcomes.The clinical question was as follows: in the population with CD, does an adequate consumption of fiber in the diet provide greater benefits than conventional therapies and normal diets to prevent CD recurrence and improve CD symptoms?The detailed search strategies for each database are listed in Observational studies;Clinical trials;Studies that analyzed the consumption of a diet rich in fiber to maintain CD remission;Studies in Spanish or English.The inclusion criteria used to select the studies that are part of this review were as follows:Studies that were conducted with animals;Studies that did not include patients with CD in their study population.The following types of studies were excluded:Study selection was carried out by two researchers, V.S.F. and M.S.P., using the inclusion and exclusion criteria mentioned above. The searches yielded 677 results (the Mendeley computer program was used to avoid duplicates); the selection process followed the flow chart detailed in the PRISMA statement . Once duTo assess the quality of the studies and detect biases, Johanna Briggs Institute (JBI) scales were used  for eachThe quality assessment was independently reviewed by two authors: V.S.F. and M.S.P. The interrater reliability was high, and any discrepancies were discussed between J-M.C.T. and J-A.L.A. until an agreement was reached.Data extraction was carried out by two researchers: V.S.F. and D-P.P.C. From each selected study, the following data were collected: (1) title and authors; (2) year and country; (3) study design; (4) sample characteristics: sample size, selection, and age of participants; (5) study objective; and (6) main results: type of fiber consumption and clinical remission rate.When interpreting the information found, the diet was considered effective when it contributed to maintaining the clinical remission of CD alone or in conjunction with other therapeutic strategies, and the intervention was considered safe as long as it did not produce adverse effects that were different from those produced by conventional therapies.For the studies selected for this review, a narrative synthesis was performed. The data were analyzed to compare results between patients who consumed a diet rich in fiber and patients who received the usual treatments or consumed common diets. Additionally, complications derived from consuming diets rich in fiber were recorded.2 statistic. I2 ≤ 25%, I2 between 26 and 50%, and I2 > 50% were used to define low, moderate, and statistically significant homogeneity, respectively [For the quantitative analysis, a meta-analysis was performed using the inverse variance method of random effects. The standard deviations (SDs) of the pre- and postparameters (high fiber diet + infliximab versus control) of each study were calculated. Statistical heterogeneity was evaluated with the IThe searches of the four databases yielded a total of 677 results. The Mendeley computer tool was used to eliminate duplicates and manage the references. After eliminating duplicates, a total of 659 results remained.Following the criteria established, 515 results were excluded. Eleven studies met the aforementioned inclusion criteria ,32,33,34All the selected studies were written in English and were either RCTs or observational studies that investigated diets rich in fiber and from which conclusions could be drawn regarding the maintenance of clinical remission in patients with CD. The characteristics of the included studies are presented in Of the 11 studies selected, 2 were RCTs ,34, 3 weThe selected studies included a total population of 5010 subjects, of whom 44% were men and 56% were women. This population ranged in age from 13 to 77 years.In the studies, there were 2389 patients with CD, and the remaining participants were patients with UC or healthy subjects. The sample included patients with all types of CD based on the Montreal classification  .Two of the eleven studies selected compared these types of diets. In general, the high-fiber diet was safer than the gluten-free diet . AdditioSpecifically, the study carried out by Schreiner P, et al.  comparedThe study carried out by Heaton K, et al.  comparedOf all the selected studies, six assessed the consumption of certain foods together with the risk of relapse or CD activity, of which five showed positive results from consuming a diet rich in fiber ,28,33,34The study published by Tasson, L, et al.  assessedThe study carried out by Dolovich C, et al.  evaluateAnother study by Mirmiran P, et al.  assessedThe study carried out by Opstelten J et al.  investigHowever, the study carried out by Brotherton C, et al.  yielded Finally, the trial carried out by Lacerda J et al.  analyzedDue to the heterogeneity of the outcome variables in these studies, it was not possible to carry out a quantitative analysis  of the benefits of a high-fiber diet alone.Three studies analyzed how the consumption of a diet rich in fiber influenced patients receiving infliximab as background therapy ,30,31. TA study conducted by Chiba M et al.  observedIn another study by the same author , 17 of tThe third study carried out by Chiba M et al.  investigp = 0.08; I2 = 0%).The results of the meta-analysis  showed aOf all the selected studies, only three showed any adverse effects. Two patients in the study by Chiba M et al.  had inteNotably, another study  reportedHowever, in the remaining studies analyzed ,31,33,34Based on the results obtained, high fiber intake through the diet is not only safe but also effective in maintaining remission in conjunction with other therapies for patients with CD.From a nutritional point of view, certain habits increase the risk of IBD flare-ups; for example, consuming red meat more than four times a week increases the risk of UC flare-ups . In the Although the efficacy of fiber in maintaining CD remission cannot be denied ,28,31,32By professional consensus, the consumption of fiber is recommended to all patients with IBD, as long as they do not have intestinal stenosis; insoluble fiber could act at the level of the intestinal lumen, producing an increase in fecal waste and increasing the risk of occlusive symptoms at the intestinal level ,40. LikeA Cochrane review reported how a diet rich in fiber produces an increase in SCFAs, promoting intestinal homeostasis and helping to control inflammation in patients with CD , as specThe consumption of dietary fiber by patients with CD was lower than that by healthy controls (4 g/day difference between groups), with a total fiber consumption of 14 g/day in patients with CD . HoweverFiber administered at controlled doses and in the form of a supplement is effective in controlling the symptoms of CD ,45. SpecTo clarify more accurately whether a nutritional intervention rich in fiber is adequate to maintain remission in patients, more RCTs are needed that compare control groups with conventional therapy groups and experimental groups and that specify the diet administered to the patients as well as the amount of fiber needed. Furthermore, such studies should be conducted for a sufficient time to ensure the reliability of the results obtained. Only two studies evaluated interventions long enough to identify the remission rates for patients clearly; the evaluation time was greater than 2 years ,31.Among the studies included in the analysis in this review ,30,31 arAmong the limitations of this review are the small number of RCTs included in the review and the lack of nutritional specifications of the diets used or investigated in the studies. In the studies included in this review, the type of fiber consumed by the subjects was not accounted for except in one study, which included soluble fiber in the participant diet . This maAnother limitation was the heterogeneity in the variables resulting from the included studies; this heterogeneity made it impossible to carry out the meta-analysis. In fact, in the meta-analysis conducted, diet interventions were different among selected studies , so it is difficult to compare them. Also, it is important to mention that these studies were low quality, and only two RCTs had a control group ,34.Furthermore, one study did not use analytical, or endoscopic criteria to measure CD activity . It is nAs strengths, the sample size in each study was sufficient to clearly reach the conclusions obtained. The studies were carried out in different parts of the world; therefore, information was collected from different populations.It seems that high dietary fiber intake can increase the remission time in patients with CD. It is a simple nutritional practice without risk for patients. However, adjuvant treatment with a diet rich in fiber should be supervised by a health professional because one of the functions of health personnel is to provide health education. Under these conditions, the consumption of a high-fiber diet is recommended.Dietary fiber intake could increase remission rates in patients with CD who achieve clinical remission with conventional therapies. Due to scarce evidence about the relationship between fiber intake and CD, we cannot recommend a specific dietary intervention. However, it can be stated that a fiber intake between 13.4 and 33.4 g/day is safe in CD patients. Also, a high-fiber diet should be an adjuvant treatment in conjunction with other therapeutic strategies to maintain remission.More studies are needed to evaluate the amount and type of fiber to improve remission rates for CD. Specifically, we believe it is necessary to conduct more RCTs that analyze conventional therapies and high-fiber diets in combination with conventional therapies, with analytical and endoscopic follow-up to determine the efficacy of the intervention.