Introduction: This study aimed to evaluate the in-hospital mortality of patients with ST-segment elevation myocardial infarction (STEMI), according to gender and other likely risk factors. Methods: This study reports on data relating to 1,484 consecutive patients with STEMI registered from June 2016 to May 2018 in the Western Iran STEMI Registry. Data were collected using a standardized case report developed by the European Observational Registry Program (EORP). The relationship between in-hospital mortality and potential predicting variables was assessed multivariable logistic regression. Differences between groups in mortality rates were compared using chi-square tests and independent t-tests.  Results: Out of the 1484 patients, 311(21%) were female. Women were different from men in terms of age (65.8 vs. 59), prevalence of hypertension (HTN) (63.7% vs. 35.4%), diabetes mellitus (DM) (37.7% vs. 16.2%), hypercholesterolemia (36.7% vs. 18.5%) and the history of previous congestive heart failure (CHF) (6.6% vs. 3.0%). Smoking was more prevalent among men (55.9% vs. 13.2%). Although the in-hospital mortality rate was higher in women (11.6% vs. 5.5%), after adjusting for other risk factors, female sex was not an independent predictor for in-hospital mortality. Multivariable analysis identified that age and higher Killip class (≥II) were significantly associated with in-hospital mortality rate.Conclusion: In-hospital mortality after STEMI in women was higher than men. However, the role of sex as an independent predictor of mortality disappeared in regression analysis. The gender based difference in in-hospital mortality after STEMI may be related to the poorer cardiovascular disease (CVD) risk factor profile of the women. In addition, we investigated whether potential disparity in mortality between women and men with STEMI could be explained by gender as an independent risk factor.This study is a part of an ongoing registry of consecutive patients with STEMI in Imam Ali Cardiovascular Center, Kermanshah University of Medical Sciences (KUMS). This is the main cardiovascular center in western Iran covering about two millions population mostly Kurdish with Caucasian race. Data adjudicated by the standards of the European Observational Research Program (EORP). Also we used the Standard for Reporting Qualitative Research (SRQR) guidelines.17 STEMI must be primary diagnosed by the emergency medical doctors. Data collection and validation of the diagnosis was then supervised by a physician who was responsible for the quality control of the project.Between July 1, 2017, and May 1, 2018, we evaluated patients admitted to the center with a presumed diagnosis of STEMI. One criterion for inclusion in the study was age ≥18 years old. Another inclusion criterion was the diagnosis of STEMI accompanied by the following criteria was required: chest pain or equivalent symptoms of more than 20 minutes duration within the last 24 hours before admission and, electrocardiographic changes consistent with new or presumed new ST-segment elevations or left bundle branch block, according to third universal definition of myocardial infarction defined by the European Society of Cardiology/ACCF/AHA/World Heart Federation Task Force for the Universal Definition of Myocardial Infarction.Patients were excluded from the study if they developed STEMI after admission in the hospital, or developed STEMI after percutaneous coronary angioplasty or coronary bypass surgery and/or hospitalized in another hospital more than 24 hours before coming to Imam Ali hospital, or who did not sign the consent form to participate in the study.Using case report forms, data were collected by a nurse and a research assistant working in the Kermanshah Cardiovascular Research Center (KCRC), who were trained in uniform protocols for patient entry and data gathering. Case report form was developed by the EORP. All completed case report forms were verified and checked for errors by the quality control physician before submission for final analysis, and then forwarded online to the EORP website. We used patients’ national identification numbers to avoid duplicate admissions to the registry. The collected data included demographic characteristics (e.g. age), clinical histories , admission process (e.g. presenting symptoms), biochemical and electrocardiographic findings (e.g. blood sugar), treatment procedures , in-hospital outcomes . Standardized definitions of all variables  were used. Likewise, mortality data  were obtained for all included cases.t tests for continuous and normally distributed variables and chi-square (or Fisher exact tests) for other variables. We compared the in-hospital mortality rates among women and men and assessed the independent role of sex in patients’ mortality using multivariable logistic regression models. Odds ratios (ORs) and 95% confidence Intervals (CIs) were calculated. The body mass index (BMI) ≥25, HTN, DM, current smoking, hypercholesterolemia, congestive heart failure (CHF), Killip class (at first presentation) ≥ II, symptom-to-balloon (STB) time> 360 minutes and door-to-balloon (DTB) time > 90 minutes (18) used as covariates, while the dependent variable was in-hospital mortality. A test was considered statistically significant if the probability value  was less than 0.05. The Statistical Package for Social Science (SPSS) software, version 23  was used for analyzing data.Baseline data including demographic characteristics were compared between men and women. Data were described using mean ± standard deviation (SD) if they were normally distributed; otherwise, frequencies and percentages were reported. Differences between subgroups were assessed using independent STB time was defined as the time between the onset of symptoms to first balloon inflation or first device delivery in the culprit vessel.DTB time was defined as the time between patient’s arrival at the PCI hospital and the first balloon inflation or first device delivery in the culprit vessel.P = 0.02). The prevalence of hypercholesterolemia, DM, HTN and prior CHF was significantly higher in women compared to men, whereas more men were current smoker  men, and 311 (21%) women met the inclusion criteria for this study. A significant difference in presenting clinical characteristics based on sex was observed. Women were, on average, older than men patients: the mean age of the women was 65.79 ± 11.34 years, whereas for the men was 59.04 ± 12.39 years (t smoker . There wP ≥ 0.05) (Primary PCI was performed for 878 patients (59.2%), 697 men (59.4%) and 181 (58.2%) women. The median DTB time and STB time (or treatment delay) were slightly longer in women than men, but the differences were not statistically significant ( ≥ 0.05) .P = 0.001). Other sex-based differences in personal and clinical characteristics of patients were shown in The mean age of patients, at death, was 66.11±11.42 for men vs 67.36 ± 9.69 for women. In-hospital mortality rates  were 5.5% (64 out of 1173) for men and 11.6% (36 out of 311) for women (P = 0.77).The role of sex in in-hospital mortality from STEMI was further examined using logistic regression model. The sex-based difference in the mortality rates was disappeared in regression analysis after adjustment for the explanatory variables listed in P = 0.03) for women vs.  for men. Age was significantly associated with the in-hospital mortality in men   .The results of this study illustrated that, in western Iran, women who presented with STEMI were significantly older and had higher prevalence of cardiovascular risk factors i.e. diabetes, hypercholesterolemia, HTN, previous CHF, but were less likely to be current smokers compared to their men counterparts. Although STEMI was managed similarly in both sexes, the in-hospital mortality rate for women was two times more than men. However, after adjustment for other characteristics such as DM and HTN, early mortality was similar for women and men.19 Furthermore, the higher incidences of DM, HTN, hypercholesterolemia, and prior CHF in women have been described in previous observations.21 Also, an international study reported that women were significantly older than men at the time of STEMI and had higher rates of HTN, DM, previous CHF, and hypercholesterolemia.22 Likewise, Birkemeyer et al reported that women were significantly older, with a higher prevalence of HTN and DM, and men were more likely to be current smokers.23The fact that women present at an older age in the current study is consistent with the findings from other studies which have reported a mean age range of 58.8 to 60.9 years for men and 65.5 to 67.5 years for women.25 this study found no significant differences in treatment with primary PCI for women and men; however, DTB and STB were delayed slightly in women compared to men. These results support the findings of previous studies that women typically experienced a delay in DTB and STB.26 In fact, the potential reasons why women delay in seeking treatment may be due to their unawareness of cardiac disease symptoms or imputing their symptoms to cardiac causes.27 Patients education campaigns and programs, especially those targeted the women, can be cost-benefit in improving women’s awareness. Other reasons could be that women, particularly in developing countries, are often dependent to men financially, and in some societies the decision to seek treatment for women is made by men.28Also, consistent with some other reports,6 Norris and colleagues found that compared to men, women with STEMI showed a higher rate of in-hospital mortality. They attributed this difference to women’s older age, sex clinical severity, and more comorbidities.29 Investigating 1548 cases of STEMI, De Luca and colleagues reported that female sex was not an independent prognostic factor of in-hospital mortality.30 In our study, the higher mortality reported among women may be due to their significantly higher rates of comorbidities, higher baseline risks, older age, and longer DTB and SBT, not associated to sex alone, which is consistent with the results of earlier studies.32 Indeed, poorer risk profile increases in-hospital mortality rates, but the risk of mortality remain the same for both genders when other factors are adjusted for.33In this study, although women’s mortality was higher than men, sex was not an independent predictor of in-hospital mortality at multivariate analysis. This result also concurs with the findings of previous studies. Barbosa et al reported that despite a high in-hospital mortality rate among women, sex was not an independent predictor of death in STEMI.20 Also, Hersi and colleagues’ survey in Saudi Arabia showed that female gender was an independent risk factor for in-hospital mortality in STEMI.24 Likewise, in a study conducted by Lawesson et al, female sex was independently linked to higher in-hospital mortality.34 Differences in inclusion criteria and patients’ selection, sample size, clinical and socio-demographic characteristics, and treatment strategies might unfold these different results.Nevertheless, some researchers have reported different results. For instance, Benamer et al described the results of a large French STEMI registry in which short term  mortality was higher in women and the impact of female sex on the mortality rate was significant.30 This conclusion was also confirmed by DeGeare and colleagues who studied 2654 cases of AMI and found that higher Killip class was associated with greater in-hospital mortality rates in both genders.35 Similarly, El-Menyar et al reported that Killip class≥ II was an independent predictor of in-hospital mortality rate in the STEMI patients.36In addition, we found that Killip class ≥II and age were significant independent predictors of in-hospital mortality in both genders the results that are consistent with findings of pervious research. Reporting the short term mortality in a population of 1548 STEMI patients treated with primary PCI, De Luca et al found that Killip class ≥ II was associated with higher in-hospital mortality rates in both genders.37Furthermore, our results demonstrated that old age was independently related to higher in-hospital mortality in men. This result is consistent with the finding of Waldecker et al, who showed that male patients had an age-related increase in in-hospital mortality rate.38 Thus, this STEMI registry may help to prioritize research projects and interventions and help policy makers to develop health programs. It may result in improving STEMI patients’ health, assists health caregivers to revise their medical services, and estimate the burden of STEMI. The gender-based differences in in-hospital mortality in STEMI, may indicate gender based differences in access and use of health care services, which warrant further considerations.In fact, the impact of sex on mortality rate in STEMI is still controversial. Disease registries, especially hospital-based registries, are valuable sources providing more reliable information about the epidemiology of cardiovascular disease (CVD).The most important limitation of the current study, as an observational registry, was that such studies have non-randomized nature and may not be able to control for the effects of cofactors, although the researchers measured and controlled for the effects of main confounding factors. Furthermore, our data were derived from a single center registry; hence, our participants may not be the representative of the whole STEMI population.In-hospital mortality was higher in women with STEMI than their men counterparts. However, sex alone, was not a significant predictor of in-hospital mortality in these patients. The gender based differences in in-hospital mortality may be explained by the more adverse clinical risk profile in women. In general, access and use of health care programs need to be improved for women, and their CVD risk factors, in particular diabetes, HTN, and hypercholesterolemia be modified to in timely manner to reduce the gender based gaps in cardiovascular health outcomes.The authors declare that there were no conflicts of interest. In addition, the authors have no financial gain related to any aspect of the study.The Research Ethics Committee at KUMS approved the study protocol (Ethics No. KUMS.REC.1395.252). Also, patients were informed about participating in the registry and signed the consent form. Patient data were kept confidential with the access limited to two of researchers and the quality control physician.This study was supported by Kermanshah University of Medical Sciences.We would like to thank the Kermanshah University of Medical Sciences for funding this project and express our sincere appreciation for the high quality collaboration of the Kermanshah Cardiovascular Research Center. We would like to thank the participants in the study.


Lactobacillaceae belonging to the Firmicutes phylum. Plasma levels of propionate and butyrate were lowered by dietary adenine and restored by GA. A negative association  was observed between Firmicutes and plasma creatinine, urea, urine N-acetyl-beta-D-glucosaminidase (NAG) and albumin. Phylum Proteobacteria on the other hand was positively associated with these markers while Phylum Bacteroidetes was positively associated with plasma SCFAs. In conclusion, the adverse changes in the composition of the gut microbiome, plasma levels of SCFAs, and biochemical indicators of renal function observed in the rats with CKD induced by dietary adenine were mitigated by GA. These findings are indicative of a link between uremia and the composition of the microbiome in connection with this disease. Dietary administration of GA to patients with CKD may improve their renal function via modulating the composition of their microbiome—a finding that certainly warrants further investigation.Chronic kidney disease (CKD) may be fatal for its victims and is an important long-term public health problem. The complicated medical procedures and diet restrictions to which patients with CKD are subjected alter the gut microbiome in an adverse manner, favoring over-accumulation of proteolytic bacteria that produce ammonia and other toxic substances. The present study aimed to investigate the effect of GA on 1) the composition of the gut microbiome and 2) on plasma levels of short-chain fatty acids. Male Wister rats were divided into four groups (six each) and treated for 4 weeks based on the following: control, dietary adenine  to induce CKD, GA in the drinking water , and both adenine and GA. At the end of the treatment period, plasma, urine, and fecal samples were collected for determination of several biochemical indicators of renal function and plasma levels of short-chain fatty acids (SCFAs) as well as characterization of the gut microbiome. Dietary adenine induced the typical signs of CKD, i.e., loss of body weight and impairment of renal function, while GA alleviated these effects. The intestine of the rats with CKD contained an elevated abundance of pathogenic Proteobacteria, Actinobacteria, and Verrucomicrobia but lowered proportions of  Chronic kidney disease (CKD), a long-term public health problem associated with considerable individual and societal burden, is estimated at present to have a global prevalence of 11–13% . MoreoveUremia and the retention of other toxins profoundly modify the barrier function and promote inflammation of the gastrointestinal tract in patients with CKD. Furthermore, both uremia and medical treatment of this condition can change the biochemical and microbial milieu in the gut . In addiPrevotellaceae and Lactobacillaceae families in the disease model. Furthermore, these same authors showed that the guts of patients with ESRD are markedly over-populated with Enterobacteriaceae, Brachybacterium, and Pseudomonadaceae, which express urease, uricase, and enzymes that biosynthesize indole, whereas the numbers of bacteria that can produce short‐chain fatty acids (SCFA) by fermentation of dietary fiber are significantly lowered , a natural product with prebiotic effects , can red50) >16 g/kg for rats. Details about toxicological indexes were published by A fresh solution of gum acacia   was prepared daily. The supplement had a median lethal dose . The experimental site was located in Muscat, Oman. The latitude of Muscat, Oman is 23.614328, and the longitude is 58.545284. Muscat, Oman is located at the GPS coordinates of 23° 36′ 51.5808″ N and 58° 32′ 43.0224″ E.Male Wister rats  were housed under standard conditions  for 7 days before treatment. These animals had (1) Group 1, the control group: standard feed and tap water(2) Group 2, the chronic kidney disease (CKD) group: chow supplemented with adenine (AD)  to induce this condition(3) Group 3, the gum acacia (GA) group: 15% (w/v) GA in the drinking water(4) Group 4, the CKD-GA group: administered AD and GA as aboveTwenty-four rats were divided randomly into four groups for 4 weeks of treatment as follows:Body weight and intake of both chow and water were monitored once weekly. On the last day of treatment, rats were placed individually in metabolic cages to collect their urine for 24 h.A total of 24 h after termination of treatment, rats were anesthetized by intraperitoneal injection with ketamine (75 mg/kg) and xylazine (5 mg/kg) and blood (5 mL) and fecal samples were collected. The blood was centrifuged at 900 g at 4°C for 15 min to separate the plasma, which was kept frozen at −80°C until analysis. The fecal samples  in each rat were snap-frozen at −80°C and stored until analysis.This study was approved by the Animal Ethics Committee .Plasma and urine concentration of albumin, creatinine, urea, and NAG were measured using commercially available kits .SCFAs in rat plasma were derivatized with 3-nitrophenylhydrazine (3-NPH) followed by quantification with liquid chromatography coupled to a triple-quadrupole mass spectrometer—a modification of the procedure described by Han and colleagues . StandarDNA was extracted from the fecal samples employing a standard protocol  and subj5′-GTCTCGTGGGCTCGGAGATGTGTATAAGAGACAGGACTACHVGGGTATCTAATCC-3′). The 16S rRNA amplicons were then utilized to prepare a library, as described previously , and theThe raw FASTQ data obtained from MiSeq were processed using QIIME2 , with asp values ≤0.05 being considered statistically significant.The plasma and urinary levels of metabolites and dietary intake are presented as means ± SEM. The values for the different groups were compared by one-way ANOVA, followed by the Bonferroni test, with p-values between the study groups were performed using the Benjamini–Hochberg false discovery rate (FDR), with an adjusted p ≤ 0.05 being considered statistically significant. Alpha diversity was analyzed using the faith_PD index at a sampling depth of 2,066 and the alpha diversities for the different groups and sites compared with the Kruskal-Wallis pairwise test. Beta diversity is presented as weighted unifrac PCoA plots and contrast between the groups and sites performed using pairwise PERMANOVA. Spearman’s correlation analysis was performed to compare plasma/urine biochemistry and SCFAs with the selected microbial taxa at three different gut sites.The compositions of the microbiomes are presented in terms of the levels of the different phyla and families. Only microbial taxons present at a level of at least 1% in at least one of the four groups were compared statistically. The bacterial compositions are presented as means, and the groups were compared using the non-parametric Kruskal–Wallis test. Furthermore, multiple comparisons of the The rats who received adenine in their diet lost approximately 16% of their initial body weight during the experimental period. These rats also consumed more water and urinated more than the controls. Both of these effects were reversed in part by the addition of GA to the adenine-containing diet as well. The relative kidney weight increased approximately three-fold in the CKD than control and GA groups. Fecal output by both the GA and CKD-GA groups was greater than for the other two groups .Administration of adenine in the diet for 4 weeks resulted in significant increases in plasma concentrations of urea and creatinine and urinary NAG , and decreased clearance of creatinine. Proteinuria, an additional indicator of renal injury, was also more pronounced in the rats receiving adenine, an effect that was reduced in part by GA. The values for all the biochemical parameters measured in the GA group were not significantly different from those of control group .Firmicutes and Proteobacteria were the most abundant phyla present, with statistically different patterns between the groups of animals. Firmicutes were more abundant in the colon than at the other two locations in the gastrointestinal tract examined . AdenineLactobacillaceae count  than in the GA and control groups. Overall, alpha diversity was higher (p ≤ 0.01) in the colon, followed by the cecum and ileum in that order. Similarly, the PCoA plots analyzing beta diversity revealed a distinct difference in the clustering patterns in the different groups .At all sites combined, alpha diversity was higher in the CKD than the control and GA groups. However, for the individual locations, this difference was statistically significant in the case of the colon and cecum only. With adenine supplementation, alpha diversity in both the colon and cecum was more pronounced (p ≤ 0.05) and additional supplementation with GA reversed this reduction. Although not statistically significant, a similar trend was observed in the case of butyrate . Plasma urea, creatinine, urine NAG, and albumin were negatively associated with Firmicutes and positively associated with Proteobacteria and Verrucomicrobia. In contrast, urine creatinine was positively associated with Firmicutes while negatively correlated with Proteobacteria, Verrucomicrobia, Pseudomonadaceae, Erysipelotrichaceae, and Staphylococcaceae. In general, at all three gut sites, all biomarkers of renal function were most closely associated with phylum Proteobacteria, Verrucomicrobia, and Firmicutes and at family level with Aerococcaceae, Verrucomicrobia, Erysipelotrichaceae, and Pseudomonadaceae.The correlation analysis between renal function biomarkers, plasma SCFAs, and individual taxa abundances supports the results obtained from the comparison of the different treatment groups . AssociaIn the present study, we evaluated the effect of GA supplementation on renal function, the plasma profile of SCFA, and gut microbiome of rats with CKD induced by dietary adenine.Following oral administration, adenine is metabolized to 2,8-dihydroxyadenine, which precipitates and forms tubular crystals that damage the renal tissues . Here, dGA is used in folk medicine to treat inflammatory conditions as well as clinically to correct uremia in patients with CKD in Middle Eastern countries . GA provIn rats with CKD, excessive accumulation of ammonia, derived from the hydrolysis of urea by microbes, promotes the growth of bacteria that express urease . Our preLactobacillus, Coprococcus, and Ruminococcaceae, were depleted in these rats and the plasma levels of their metabolic products propionate and butyrate lowered (Here, we observed significant differences in the relative abundances of 62 bacterial clades, in both the alpha and beta indices of diversity, and in the level of two SCFAs between the different study groups. The relative abundance of Firmicutes, for which the main metabolic end-product is butyrate , was low lowered . In partEnterobacteriaceae and Verrucomicrobiaceae express tryptophanase, which is essential for the conversion of tryptophan into indole. A positive correlation in the count of plasma creatinine and urea and gut Proteobacteria may thus explain weak markers of renal function in CKD rats. In contrast, SCFAs, such as propionate and butyrate, produced in connection with the fermentation of fibers, improve renal function by attenuating inflammation, oxidative stress, and apoptosis (Proteobacteria is a diverse phylum with a sullied reputation including several well‐known opportunistic pathogens, such as Enterobacteriaceae, Helicobacteraceae, Pasteurellaceae, and Pseudomonadaceae . Vaziri poptosis .Lactobacillaceae of the Firmicutes phylum are well-known for their role in digesting carbohydrates, as well as their probiotic properties (Lactobacillaceae counts at the different intestinal locations were significantly reduced in the CKD rats, whereas additional supplementation with GA partially or entirely reversed this change. Numerous studies demonstrated the beneficial effects of dietary supplementation in CKD patients with Lactobacilli alone or in combination with prebiotics. (Lactobacillaceae CKD rats can explain their higher blood levels of urea and creatinine. Alternatively, these beneficial microbes and GA may act as synbiotics, which are known to improve the composition of the microbiome and, most likely, renal function as well (operties . Here, tbiotics. . These mbiotics. . Accordi as well .SCFAs exert multiple beneficial effects on host homeostasis and aid in recovery from disease through their anti-inflammatory, immune-modulatory, and anti-oxidative properties . The thrPlasma levels of SCFAs are reduced in patients with CKD  and thisClearly, SCFAs exert numerous beneficial effects on health. For example, administration of propionate to patients undergoing hemodialysis alleviated their levels of pro-inflammatory parameters, improved insulin resistance and iron metabolism, and was associated with a better quality of life . ButyratNotably, both animal  and clinThe extrapolation of the findings of this study may be limited to male gender only. Methods used in the current study did not allow for testing impact on microbiome in a mechanistic work. For example, changes in levels of cytokines could have been measured to investigate the link between SCFAs and inflammation.In conclusion, the observations documented here indicate clearly the importance of the gut microbiome and its metabolites in connection with CKD as well as the ability of supplemental GA to enhance both the growth of beneficial bacteria in the gut and the release of SCFAs that may improve renal function. Several bacterial taxa are associated with renal function and plasma SCFAs. Dietary manipulation of the microbiome in this fashion might provide a novel therapeutic approach to inhibiting the progression of CKD, and further examination of this possibility is certainly warranted. Further work is needed to investigate gut wall integrity, intestinal epithelial barrier function, and quantitative/qualitative alterations of the gut microbiota and their products that associate with the uremia and kidney failure.


Some studies suggest that as much as 40% of all causes of death in a group of patients with schizophrenia can be attributed to suicides and compared with the general population, patients with schizophrenia have an 8.5-fold greater suicide risk (SR). There is a vital need for accurate and reliable methods to predict the SR among patients with schizophrenia based on biological measures. However, it is unknown whether the suicidal risk in schizophrenia can be related to alterations in spontaneous brain activity, or if the resting-state functional magnetic resonance imaging (rsfMRI) measures can be used alongside machine learning (ML) algorithms in order to identify patients with SR.Fifty-nine participants including patients with schizophrenia with and without SR as well as age and gender-matched healthy underwent 13 min resting-state functional magnetic resonance imaging. Both static and dynamic indexes of the amplitude of low-frequency fluctuation (ALFF), the fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity as well as functional connectivity (FC) were calculated and used as an input for five machine learning algorithms: Gradient boosting (GB), LASSO, Logistic Regression (LR), Random Forest and Support Vector Machine.p < 0.05). Significant classification ability was also reached for GB and LR using fALFF and ALFF measures.All groups revealed different intra-network functional connectivity in ventral DMN and anterior SN. The best performance was reached for the LASSO applied to FC with an accuracy of 70% and AUROC of 0.76 (Our findings suggest that SR in schizophrenia can be seen on the level of DMN and SN functional connectivity alterations. ML algorithms were able to significantly differentiate SR patients. Our results could be useful in developing neuromarkers of SR in schizophrenia based on non-invasive rsfMRI. Schizophrenia research suggests that as much as 40% of all death causes in this group can be attributed to suicides , while 2Functional magnetic resonance imaging (fMRI) is a non-invasive, widely employed method allowing one to measure activity of a human brain. Resting state (rs), in turn, is considered highly effective as it captures 60–80% of the brain’s total activity . FurtherPrevious studies indicate gray matter volume reduction in dorsolateral prefrontal cortex (DLPFC), superior temporal gyrus, as well as insular cortex in patients after suicide attempt, compared to the ones without suicide attempt in the past , whereasIn recent years, there has been a growing number of machine learning (ML) applications on rsfMRI data in order to make prognostic evaluation and to differentiate between various groups or conditions . Lately,In the current work, our objective was to conjoin ML methods with rsfMRI data in order to investigate whether the selected classifiers allow differentiating between schizophrenia patients with and without a suicide risk. Ultimately, five algorithms such as Gradient Boosting (GB), Least Absolute Shrinkage and Selection Operator (LASSO), Logistic Regression (LR), RF, and Support Vector Machine (SVM) were performed to increase the reliability of diagnostic accuracy. Each metric presents a different degree of complexity; therefore, establishing their separate and combined precision allows gaining a wider picture in the aforementioned classification. Moreover, the article aims at explaining the association between the resting-state brain activity and suicide risk among schizophrenia patients; thus, stationary as well as dynamic measures with sliding windows approach were calculated. Based on the literature, the authors hypothesize (a) varied neural activity in the regions included in DMN, SN, and SMN networks to be involved in suicide risk in patients with schizophrenia; (b) that the predictive ability of classifiers will be better while using dynamic indexes as the features in comparison to the static ones; (c) that the results of ML-based discrimination will differ using diverse parcellation approaches; (d) ML-based algorithms to discriminate between SR and NSR groups with the accuracy exceeding 50%.A total of 66 participants were recruited for the study. The clinical group consisted of 43 patients with paranoid schizophrenia diagnosed according to the ICD-10 criteria. The clinical group covered two subgroups: 24 patients with acute suicidal risk (SR) and 19 patients without such risk (NSR). The control group (HCs) consisted of 23 individuals matched in terms of gender and age with a clinical group, without diagnosis of mental disorder or a history of mental illness in first-degree relatives. All the participants were right-handed, as measured by the Neurological Evaluation Scale . The incSuicidal risk was assessed with the Polish adaptation of Suicide Behavior Questionnaire—Revised (SBQ-R) , with thMRI data were acquired using a 3-T Siemens Skyra MR System . Anatomical images were obtained using sagittal 3D T1-weighted MPRAGE sequence with TR = 2,300 ms and TE = 3.9 ms. A total of 13 min of functional resting-state BOLD images was acquired using a gradient-echo single-shot echo planar imaging sequence with the following parameters: FOV = 256 mm; TE = 27 ms; TR = 2060 ms; voxel size = 3 mm × 3 mm × 3 mm, with no gap. Altogether, 39 interleaved transverse slices and 400 volumes were acquired. During the resting-state procedure, the subjects were instructed to keep their eyes open and to think of nothing particular. They were also asked not to fall asleep, which was controlled using an infrared binocular eye tracker . In addition, during the EPI sequence, neutral gray background was presented using a MRI-compatible LCD screen and Siemens Head Coil Viewing Mirror. Both structural and functional sequence details are in 3. The 24 motion parameters , dorsal default mode network (dDMN), anterior salience network (aSN), posterior salience network (pSN), and SMN , Amplitude of Low Frequency Fluctuations (ALFF), Fractional Amplitude of Low Frequency Fluctuations (fALFF), and Functional Connectivity (FC). Each measure has its static and dynamic equivalent, and each measure was extracted for both atlases  and 264 × 1  matrices, consisting of a single value for each brain region among all 390 time points. Z-transformed correlation coefficients were obtained for each brain atlas, which resulted in 264 × 264 as well as 116 × 116 matrices for each participant. The lower half and diagonal values were removed and not used as features for ML algorithms, so that the total of 6,670 and 34,716 The dynamic mALFF, mf/ALFF, and mReHo indexes were computed using the Temporal Dynamic Analysis module of Dpabi  using a fmin, where fmin is the minimum frequency of the time series; a similar approach was used among others in the work of fmin after band-pass filter equals 0.01 Hz (100 s), and for this reason, window size was set to 50 TR (103 s) length and was shifted by 1 TR (2.06 s). The full time series was divided into 341 windows for each participant. As in case of stationary maps, dynamic maps were segmented using AAL and Power atlases. As a result, each participant gets a matrix of size 341 × 116 for AAL atlas and 341 × 264 for Power et al. atlas for dynamic ReHo (dReHo), dynamic ALFF (dALFF), as well as dynamic f/ALFF (df/ALFF). Each column represented a brain region and rows were populated with a single value for each window. Dynamic functional connectivity (dFC) was computed using the same window size, shift, and method via DynamicBC v.2.2  and 11.838156 (Power) z-score values used as an input for classification algorithms.According to previous work of BC v.2.2 . After tThe authors used a selection of the most effective classification algorithms, each with a different level of complexity: LR , LASSO , SVM Bo, RF Ho,, and GB https://github.com/gmum/schizo_fmri.The source code is available at The dataset was divided into train and test sets of approximately equal sizes  with stratification. The training dataset was used to train a classifier pipeline consisting of optional data standardization and dimensionality reduction using Principal Component Analysis (PCA) steps and of the actual classifier. A grid search with fivefold cross-validation was performed to find the optimal hyperparameters. The entire hyperparameter grid search and training procedure is illustrated in For static data, the model simply accepts the entire data of selected measure types for the given patient. For dynamic data, the model is given only a single window and, thus, predicts a binary label for each window. An aggregation scheme is needed to make a final prediction for a patient. For this purpose, we applied a simple thresholding and counting scheme. Window results are first transformed to binary results using 0.5 as the threshold value. The final result was defined as the ratio of positive results to the total number of windows.Area Under Receiver Operating Curve (AUROC) was used as the score metric for grid search cross-validation procedure, and both AUROC and accuracy of the final classifier were evaluated on the test dataset.p-value of each AUROC score was calculated in order to determine the statistical significance of the obtained results. To do this, 1,000 permutations of the target labels were generated. Then, for each permutation, the classifier was retrained on the permuted labels, and its AUROC score was measured. The p-value was defined as the ratio of runs that achieved a score greater than or equal to the score of the original classifier , mental pain (TPS), severity, and illness duration between the SR and NSR groups. One-way analysis of variance (ANOVA) was used to check for possible differences in age, mean FD, and education (in years) between SR, NSR, and HCs groups, and the Kruskal–Wallis H test was used to compare gender differences.Two-sample p < 0.05.One-way ANOVA was used to investigate possible differences in FC among three rsfMRI networks between SR, NSR, and HCs groups. The results were corrected with the post hoc test was used to investigate the differences in static ALFF, fALFF, ReHo between SR, NSR, and HCs. Age, gender, and mean FD were used as covariates. The same set of analyses was applied to compare the group-level temporal variability of ALFF, fALFF, ReHo, and FC. Temporal variability for ALFF, fALFF, and ReHo was expressed as a coefficient of variations (SD/mean) and, for FC, as a variance calculated across sliding-window dynamics, and then compared using one-way ANOVA with FDR correction. The statistical significance level for ALFF, fALFF, and ReHo analyses was set as pFWER < 0.05 with 5,000 times permutation using Permutation Analysis of Linear Models  = 2.13; p = 0.1282], gender , and head motion  were found among the three groups. SR and NSR groups were significantly different in SBQ-R score  and illness duration , but no differences were found in the case of TPS scores  The range of SBQ-R score in the SR group was 8–17 points  and anterior SN   and NSR and HCs groups . In the case of anterior SN, post hoc tests indicated differences between SR and NSR groups . No differences were found among dorsal DMN, posterior SN, or SMN between the three groups. Temporal variability of FC, calculated at each voxel for the two atlases, showed that the three groups were significantly (p < 0.001) different in total FC variability measured using AAL, as well as Power atlases. Post hoc tests with FDR correction showed that in the case of both atlases, FC variability was significantly different between SR and NSR, between SR and HCs, and between NSR and HCs groups  . Post hos groups ,2.The 10 most important features of amplitude of low-frequency fluctuations (ALFF) for LR as well as of Functional Connectivity for LASSO classifiers are presented in p < 0.05. (1) The LASSO applied to static functional connectivity with Power atlas reached an accuracy of 70% and an AUROC of 0.76. (2) The LR algorithm applied to dynamic ALFF with AAL atlas reached an accuracy of 65% and an AUROC of 0.75. (3) The GB algorithm applied to static fALFF with AAL atlas reached an accuracy of 65% and an AUROC of 0.74. It can be seen that AUROCs of the majority of variants were at chance level, even when accuracies were above 50%. In short, the obtained results suggest that the combination of LASSO algorithm and static functional connectivity calculated on 264 ROIs provide superior accuracy/AUROC of classification between SR patients and non-SR patients and allow correct classification of 14 out of 20 SR patients.Three variants of ML algorithm and rsfMRI measures turned out to be significant at In the present article, a successful discrimination between schizophrenia patients with and without a suicide risk using ML algorithms and rsfMRI data was demonstrated.Ipso facto, the presented study is the first attempt to find rsfMRI features that allow detecting the risk of suicide in schizophrenia with the use of the ML algorithms. Moreover, this is the first work using rsfMRI to explain the differences in brain activity, which might be associated with suicide risk in schizophrenia patients. Above that, unlike most of ML–fMRI studies focused on classifying suicidal participants, the authors used five various ML classifiers. The results of conventional analyses showed that patients with and without suicidal risk, as well as the healthy controls, demonstrated different patterns of temporal variability of dFC and FC, with the latter being an important feature for ML classification. Furthermore, ALFF and fALFF measures also contributed to ML-based classification, but no significant differences in the above measures were found in the conventional group analyses.Although previous studies developed the rsfMRI-based ML classification models capable of distinguishing suicidal patients with different diagnoses, such as anxiety disorder, depression, or borderline personality disorder , to the Numerous fMRI studies indicate the association of suicide-related behaviors and prefrontal cortex alterations due to its role in decision-making as well as action planning . Other sImportantly, our results from conventional static FC analyses confirm the aforementioned results, revealing functional connectivity differences in ventral DMN and anterior SN between SR and NSR patients. The above dissimilarity was also apparent between NSR patients and HCs. Moreover, The LASSO algorithm, applied on static functional connectivity data, allowed the discrimination between SR and NSR patients, supporting our hypothesis. Furthermore, all the three groups varied from each other in the case of temporal variability of dFC with the use of both AAL and Power atlases.According to another hypothesis, all five ML algorithms presented different classification performance. The LASSO, applied on static functional connectivity without PCA on Power atlas, achieved 70% accuracy and an AUROC of 0.76, proving to be the best ML classifier used in the study. As a result, LASSO allowed the correct classification of 14 out of 20 suicidal patients. The possible reason why the LASSO outperforms the other classifiers is the type of its regularization loss term. The processed dataset has high dimensionality but very few samples, which could possibly make the standard classifiers heavily overfit to the train set and therefore perform poorly on the test set. As a result, a regularization method needs to be used in order to reduce overfitting and increase generalization. The L1 cost used in LASSO has a property of much stronger parameters’ shrinkage due to its diagonal regularization contour, leading to a more sparse model.Noteworthy, raw performance of the classifiers differed depending on the selected parcellation scheme. However, contrary to our assumptions, the dynamic measures did not improve the prediction ability of ML classifiers compared to static measures. As far as the authors are aware, none of the previous studies used ML-based classifiers to discriminate between SR and NSR schizophrenia patients. Further studies should consider to enlarge sample size in order to demonstrate the replicability of our study.The conducted study has some limitations. Firstly, EPI sequence was introduced to participants after the structural scans (T1–MPRAGE) and not before them, which could influence the results. Secondly, results may possibly depend on the size of the smoothing kernel. Another noteworthy limitation of this study is the restricted sample size; thus, the presented results should be interpreted with caution. Further studies should consider extending the sample size by adding the control group to the input training data. Moreover, the specific window size as well as arbitrarily chosen atlases could influence the results. What is more, the high number of features may cause high susceptibility to any noise signal; therefore, distinctive features could be possibly different in another sample size, i.e., patients. Based on the literature, we have also decided to include the global signal, which is not always considered to be beneficial. Additionally, further studies should incorporate a semi-supervised approach with a pre-training phase using the data of HC.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation, to any qualified researcher.The studies involving human participants were reviewed and approved by Jagiellonian University Bioethics Committee. The patients/participants provided their written informed consent to participate in this study.BB: conceptualization, methodology, validation, formal analysis, investigation, writing – original draft, writing – review and editing, visualization, and project administration. AMS: formal analysis, investigation, writing – original draft, writing – review and editing, and visualization. IP: methodology, software, validation, writing – review and editing, and supervision. BW: software, formal analysis, writing – original draft, and visualization. DM: resources and writing – original draft. AC: investigation, resources, and funding acquisition. MF: writing – review and editing. MS: resources. DD: resources. TM: resources, writing – review and editing, supervision, and funding acquisition. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The COVID-19 outbreak, in a few weeks, overloaded Italian hospitals, and the majority of medical procedures were postponed. During the pandemic, with hospital reorganization, clinical and learning activities performed by residents suffered a forced remodulation. The objective of this study is to investigate how urology training in Italy has been affected during the COVID-19 era. In this multi-academic study, we compared residents' training during the highest outbreak level with their previous activity. Overall 387 (67.1%) of the 577 Italian Urology residents participated in a 72-h anonymous online survey with 36 items sent via email. The main outcomes were clinical/surgical activities, social distancing, distance learning, and telemedicine. Clinical and learning activity was significantly reduced for the overall group, and after categorizing residents as those working only in COVID hospitals, both “junior” and “senior” residents, and those working in any of three geographical areas created . A significant decrease in outpatient activity, invasive diagnostic procedures, and endoscopic and major surgeries was reported. Through multivariate analysis, the specific year of residency has been found to be an independent predictor for all response modification. Being in zone 3 and zone 2 and having “senior” resident status were independent predictors associated with a lower reduction of the clinical and learning activity. Working in a COVID hospital and having “senior” resident status were independent predictors associated with higher reduction of the outpatient activity. Working in zone 3 and having “senior” resident status were independent predictors of lower and higher outpatient surgical activity, respectively. Working in a COVID hospital was an independent predictor associated with robotic surgical activity. The majority of residents reported that distance teaching and multidisciplinary virtual meetings are still not used, and 44.8% reported that their relationships with colleagues decreased. The COVID-19 pandemic presents an unprecedented challenge, including changes in the training and education of urology residents. The COVID era can offer an opportunity to balance and implement innovative solutions that can bridge the educational gap and can be part of future urology training. The acute respiratory disease caused by coronavirus (SARS-CoV-2 or 2019-nCoV) and known as coronavirus disease 2019 (COVID-19) spread initially throughout China and from February 2020 in Europe and the USA  among urology residents.Our online survey was sent to all 577 Italian urology residents via email on April 9th, 2020. The population was stratified on the basis of the residency year ; type of hospital ; and geographical area on the basis of the number of COVID-19 cases .We emailed a 72-h anonymous online survey—the time frame in which the survey could be answered—featuring 36 items . The surGeneral information: academic or nonacademic hospital, the region of Italy, the year of residency, and the type of hospital;Pre-COVID training information (October or November 2019): weekly business hours, weekly outpatient clinical activity, monthly invasive diagnostics, monthly minor surgeries, monthly endoscopic surgeries and monthly major surgeries divided between open or minimally invasive;During COVID training information (March 2020)—same as pre-COVID training information;Other information related to COVID period—use of distance teaching, telemedicine, relation with colleagues and PPE availability/usage.The survey was conducted in Italian according to the Checklist for Reporting Results of Internet E-Surveys . Four ItThe survey was distributed by contacting directors of all Italian residency programs. In addition, “Senato degli Specializzandi,” an association that includes the majority of Italian residents, has been asked to share the survey.The objective of this study was to compare residents' clinical and surgical activities in the month of March 2020  with their activity during a non-COVID-19 period (October 2019 or November 2019). The role of distance teaching tools in residents' education, the use of telehealth medicine at academic centers, and the impact on social relationships among colleagues were also evaluated.A descriptive analysis of the response of each of the questions of the survey was carried out. The association between variables was tested by the Pearson chi-square test or the Fisher exact test.A comparison of the responses given regarding the pre-COVID and during-COVID training information was performed using the nonparametric McNemar test.p ≤ 0.05. The following variables were considered: zone, COVID hospital, and year of residency. Variables that were statistically significant in the univariate analysis were used in the multivariate analysis. A multivariate logistic regression model was developed using stepwise regression (forward selection) to compare the predictive power of different factors. The limit on testing a variable and removing it were p = 0.10 and p = 0.15, respectively.The odds ratio (OR) and 95% confidence interval (95% CI) were estimated for each variable. Statistical significance was set as A multiple correspondence analysis (MCA) was performed as a descriptive technique designed to analyze simple two-way and multiple-way tables. MCA was used to evaluate the possible relationships among all the variables and to identify specific profiles . AssociaThe RStudio graphical interface v.0.98 for R software environment v.3.0.2 were used for all analyses.Overall, 387 (67.1%) of the 577 Italian urology residents completed the survey. A graphic representation of the regions of the hospitals of origin is depicted in p < 0.0001), for those working only in COVID hospitals (p < 0.0001), for both “junior” and “senior” residents (both p < 0.0001) and for those working in any of the three geographical areas . A comprehensive histogram overview concerning the cumulative response modification between pre- and COVID period for all items addressed in the survey is represented in Clinical and learning activity at the hospital was significantly reduced for the overall group (p < 0.0001). Outpatient surgical activities significantly decreased in the overall group (p < 0.0001), for residents working only in COVID hospitals (p < 0.0001), for both “junior” and “senior” residents (both p < 0.0001) and for those working in all of the three geographical areas , but it was not significantly reduced for those working in non-COVID hospitals (p = 0.23).A significant decrease in outpatient and invasive diagnostic procedures was reported in the overall population and after categorizing for COVID hospital, year of residency, and geographical area , for residents working in either COVID or non-COVID hospitals (p < 0.0001), for both “junior” and “senior” residents (both p < 0.0001) and for those working in the zone 1 and 2 . Histograms focusing on the differences among the sole surgical activities categorized according to geographic area, residency year, and COVID or non-COVID hospital are presented in Endoscopic activity significantly decreased for the overall group and for the subgroups considered. Open and minimally invasive major surgical activity significantly decreased in the overall group (p < 0.0001) and zone 2  compared to zone 1 of origin, and “senior” resident status  were independent predictors associated with a lower reduction of the clinical and learning activity. Working in a COVID hospital  and “senior” resident status  were independent predictors associated with higher reduction of the outpatient activity. Working in zone 3  compared to zone 1 and “senior” resident status  were independent predictors associated with lower and higher outpatient surgical activity, respectively. Working in a COVID hospital  was an independent predictor associated with robotic surgical activity as assistant  decreased. Finally, p = 0.03) was an independent predictor of the reduction of relationships with their colleagues, while working in zone 3  was an independent predictor of the increase of relationship with their colleagues , we could not find a significant reduction of clinical/learning activity and of outpatients' surgery. This was most likely due to an activity that has been less affected in all the hospitals not dealing with COVID patients, where nonurgent and elective surgery was maintained. This was confirmed by analyzing the attendance of residents during endoscopic urological interventions.Nevertheless, multivariate analysis showed that being in zone 2 and 3 and having senior resident status were associated with a lower reduction of clinical/learning activity and outpatient surgical activity, while working in a COVID hospital and having senior resident status were predictors associated with a higher reduction of the outpatient activity. These data confirm that COVID hospitals and zones with a higher number of SARS-CoV-2 cases are more involved in all clinical activity that could be deferred.The multiple correspondence analysis indicates that residents working in zone 1 have been affected by a bigger change in their activity compared with those in zone 2 and an even a bigger change with zone 3.On the other hand, it should be noted that distance teaching and telemedicine are still far from being considered a daily routine : even duFinally, the use of PPE reflects the actual shortage; surgical masks and gloves are the only equipment widely used with 89.8 and 72.5% of residents who are wearing them, respectively, outside an OR context. Generally, residents saw a reduction of relationships with their colleagues. Interestingly, this was higher overall in COVID hospitals compared with non-COVID hospitals. However, a significant increase in relationships with colleagues was noted in high-risk zones compared to low-risk zones. This apparent contradiction could be related to the fact that in the areas with very high death rates, support among colleagues increased to cope with the catastrophic situation that some hospitals were living through. Indeed, the pandemic will have meaningful psychological consequences on residents and on health care workers generally. Further studies are needed to carefully analyze in detail these aspects with particular attention to the risks of anxiety, depression, burn-out and all stressful consequences  of health systems was performed in 2000, and the Italian health care system was the second best, after France. Even the most recent evaluation confirmed that the Italian health care system is the third best in the world , 10. UroThe pandemic could be even the cause of different diagnostic and therapeutic strategies for minimizing the potential exposure of patients to hospitals, postponing low-risk surgeries, and delaying or reconsidering certain therapies . The risLooking toward the future, we should start thinking of different ways to provide adequate training in urology, and we should consider virtual learning platforms, for example, using web platforms such as Google Classroom, Google Meet, Zoom, or Webex –21. AlthSuch “cognitive training” might allow users to rehearse a procedure without carrying it out, offering a relative advantage while not necessitating electronic resources or particular costs or fees. This cognitive-driven approach has been demonstrated to be significantly productive with regard to other different fields, such as aviation, sports, and musical activities; while research is still limited, although it is proposed for surgical education.In their comprehensive literature review of mental training in surgical education, Davison et al. focused on the act of performing motor tasks in the “mind's eye” and on the potential for training outside the operating room. The authors found that the majority of research studies reported mental training to be useful. Even if the cumulative level of evidence from the analysis was still relatively low, lacking standardized methodology and acknowledging a small sample size, the majority of the studies demonstrated a significant efficacy and impact, especially among the more experienced surgeons . Among uOur analysis has several strengths, but there are some limitations that should be underscored: we evaluated only the situation in Italy, and we did not extend the survey to other European countries; the web-based system could leave out certain clinical and learning aspects while an objective assessment could not be reached because responders offered their personal judgment, not always reflecting real life. Finally, 67.1% of subjects who completed the survey during the 72 h allowed could be considered not fully representative of all urology residents.The COVID-19 pandemic presents an unprecedented challenge for our health system, including the training and education of urology residents. The dramatic change in residents' daily routines is reflected in a decrease in all clinical and learning activities. The COVID era can offer an opportunity to balance and implement innovative solutions that can bridge the educational gap and can be part of future urology training.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Department of Urology internal Ethical Committee, Sapienza University of Rome. The patients/participants provided their written informed consent to participate in this study.GB, MF, and AS: study concept and design. NL, AA, MCe, EC, MCa, AMi, BR, WA, AP, FP, RD, MD, DA, SCi, GR, GLuc, GLi, GLug, PD, PG, FS, CTr, RSca, RP, CTe, MB, PV, MMad, AD, PB, GG, MR, LD, EB, RSch, CS, AV, FM, AB, FDa, CP, VS, SD, AG, LS, MMar, EM, GC, LC, FG, GM, AT, MG, VM, ED, and OC: acquisistion of data. FDe, AMa, GB, MF, SCo, and MMag: analysis and interpretation of data. IS: statistical analysis. AS, ED, and OC: supervision. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer SL declared a shared affiliation with several of the authors to the handling editor at the time of review.


A growing body of evidence supports the fact that optimal health-related quality of life is largely dependent on patient competence in symptom perception. However, many studies have reported poor symptom perception in patients with heart failure. In China, there has been no previous research on assessing the symptom perception ability of patients with heart failure. This study aimed to describe how Chinese patients with heart failure perceive their symptoms, as well as to explore their influencing factors. A theory-based, descriptive, correlational cross-sectional design was used in this study. Data on symptom perception and factors related to symptom perception were collected via structured interviews and medical records. A convenience sample of 208 hospitalized patients was enrolled. The degree of symptom perception in this study was at a high level. The results showed that the level of depression, the New York Heart Association functional class, the left ventricular ejection fraction, and educational background were identified as independent factors of symptom perception in Chinese patients with heart failure. The degree of symptom perception of patients with heart failure was affected by personal, psychological, and physiological factors. Health policy and healthcare providers should pay more attention and deepen the understanding to Chinese patients with heart failure to provide better healthcare. Heart failure (HF) has become a global disease, with an increasing prevalence of about 26 million people . Projectsymptom perception as including both symptom monitoring and symptom recognition, as well as body listening, symptom interpretation, and labeling [More than 50% of HF patients were found to be re-hospitalized with HF-related symptoms within six months after discharge . Symptomlabeling ,11. HF patients are always under great pressure in managing their symptoms . PatientSome research studies have described factors influencing symptom perception in the heart failure field ,16. Howeself-care maintenance, symptom perception, and self-care management [The theoretical framework for the study was the Theory of Heart Failure Self-Care (revised and updated) . The thenagement . Self-canagement . The theory also indicated that situational characteristics  and self-efficacy might make the self-care process unique to each HF patients. Contributing factors influencing decision about the implementation of the whole self-care process include the individual’s experiences, knowledge, skill, and values . ExperieTwo propositions of the theory were outlined in this framework: (a) symptom perception was required for successful self-care management, and (b) decisions about self-care might be conscious or subconscious; these decisions reflect choices driven by the interactions of the person, problem, and environmental factors. Self-care management was measured by the duration of symptoms, which represented patients’ care-seeking behaviors in this study.A descriptive, correlational cross-sectional design was used. The study was performed from May 1, 2019 to October 31, 2019. Patients diagnosed with acute heart failure were consecutively recruited from five nursing units in three departments of cardiology of three university-affiliated hospitals in Wuhan, China. This study was approved by the Ethics Committee of the School of Medicine, Wuhan University (2019YF2040). A written informed consent was obtained from each participant before they participated in the study.This study used a convenience sample approach to recruitment. A prior power analysis was used to determine proper sample size for correlation and regression analysis. By using G*Power 3.1.9.2 computer program software , based on a power of 0.80, an effect size of 0.30, and an alpha level of 0.05, the estimated sample size for correlation was 82. Meanwhile, on the basis of 10–20 participants per variable in the multivariate regression model, together with the ability to meet the aims, the minimum sample size for regression analysis was 180. Considering the heterogeneity of the population, 15% (27) was oversampled, and the estimated minimum sample size for in this study was 207 participants.We included hospitalized patients admitted to the hospital due to a deterioration of heart failure. The inclusion criteria were patients (1) diagnosed with acute heart failure (not associated with a reversible cause); (2) over 18 years of age; (3) within 72 h of admission; (4) alert and able to understand the study, and to provide written informed consent; (5) clinically stable including vital signs stable and not vented or on continuous positive airway pressure; and (6) able to read and write Chinese at the fifth grade level.We excluded patients with (1) major uncorrected hearing impairment, (2) major psychiatric illness , (3) major uncorrected visual impairment, and (4) diagnosis of dementia.Participants were identified by reviewing the daily admission sheets and then were contacted as potential participants by the primary research investigator within 72 h after admission. Prior to participation in the study, each participant received a written consent form with information regarding the purpose, the content, and the significance of the study. Participants were informed about the time, the location, and the duration of data collection, as well as the possible benefits and risks of their participation. After clarifying the above-mentioned components and answering the participants’ questions, patients who agreed to take part in the study were asked to sign the consent form. After the informed consent, data from medical records and the participant were collected by the primary investigator. This procedure was continued to complete the sample size. In order to standardize the procedure, the primary investigator read the questions out loud to all participants. All questions were answered by the participants themselves. The sociodemographic questionnaire: The demographic profile tool was researcher developed. Participants’ sociodemographic data were collected using a structured questionnaire. The following variables were included: age, gender, ethnicity, marital status, educational level, living arrangements, perceived economic status to meet needs, and religious affiliation.Basic clinical information: This part included the following information: duration of heart failure (collect in months), NYHA functional class, recent LVEF , NT-proBNP, duration of symptoms , and comorbid conditions, which were evaluated by the Charlson Comorbidity Index (CCI). NYHA functional class was routinely documented by physicians and was confirmed by the primary investigator who was trained to assess self-reported HF symptoms and limitations. Duration of heart failure and duration of symptoms was retrieved by interviews and confirmed by medical records. NYHA functional class, recent LVEF, and NT-proBNP were reviewed in the medical record. CCI is a world-wide tool which is used to assess the 10-year survival/mortality risk in patients with several co-morbidities .Cognitive function: The Montreal Cognitive Assessment (MoCA) is a brief cognitive screening tool that can better detect mild cognitive impairment . The ChaDepression: The Patient Health Questionnaire (PHQ-8) was used to quickly assess depressive status in this study. The Patient Health Questionnaire eight-item depression scale consisted of eight items from the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) . There wAnxiety: The Patient-Reported Outcomes Measurement Information System (PROMIS)  Short FoSymptom perception: The Heart Failure Somatic Perception Scale v.3 (HFSPS) was an 18-item Likert scale used to assess perceived symptom burden of HF symptoms . The HFSp-values equal to or less than 0.05 were considered as significant in this study. Clean up and analysis of missing data and outliers was performed before analyzing the data. Pearson (pr) and Spearman (sr) correlations were used to detect bivariate correlations of symptom perception and continuous variables. Correlations of symptom perception and binary variables was explored by using independent sample t-test (t) or non-parametric test (t’). Correlations of symptom perception and polytomous variables were explored by using single factor analysis of variance (F) or Welch test, and least significant difference (LSD) test was used to perform post hoc multiple comparisons. The α value was 0.05. To control the effects of covariates, all the demographic and clinical variables were analyzed in simple correlation analysis. Hierarchical multiple regression was used to further detect multivariable relationship of symptom perception and selected variables. For analysis, logarithmic transformation was used to normalize the distribution of NT-proBNP. For educational background of “bachelor or above”, perceived economic status to meet needs “less than enough”, NYHA functional class I, minimal depression was set as a reference category for each corresponding variable in hierarchical multiple regression.Analyses were conducted using Epidata version 3.1  and IBM SPSS version 23.0 . All comparisons were two-tailed, and A total of 285 hospitalized HF patients’ medical records were reviewed and invited, with 38 patients excluded , and 39 patients refused to participate in the study. The remaining 208 patients completed the structured questionnaire with an effective rate of 100% (208/208). As shown in The HFSPS was used to assess patients’ symptom perception ability. rs (208) = −0.221, p = 0.001) was negatively correlated with total HFSPS score. Meanwhile, NT-proBNP (rp (208) = 0.226, p = 0.001) was positively correlated with total HFSPS score. The level of anxiety (rs (208) = 0.179, p = 0.010) was also positively correlated with total HFSPS score. No significant correlation was found between gender, living arrangements, ethnicity, or religion and symptom perception in Chinese patients with heart failure. The differences in symptom perception among different educational levels (Welch (208) = 3.676, p = 0.023), different levels of perceiving economic status to meet needs (F (208) = 4.361, p = 0.014), different levels of depression (F (208) = 5.426, p = 0.001), and different NYHA functional classes (F (208) = 9.775, p = 0.000) were statistically significant and not identical. The results of single factor analysis among symptom perception and variables are shown in F = 4.335, p < 0.001), suggesting that there was a linear correlation between dependent variables and independent variables, and the inclusion of these four independent variables helped predict the dependent variables. Each included variable was independent of the other , and the variable tolerance was higher than 0.2 and variance inflation factor (VIF) was lower than 5, indicating that there was no multicollinearity in this study. In this model, 25.3% of the variation in symptom perception could be explained by NT-proBNP, level of anxiety, LVEF, educational level, perceived economic status to meet needs, and level of depression . The final model was statistically significant (p = 0.026). Patients with primary school/below educational background, compared with bachelor or above educational background, had a significantly higher symptom perception ability . There was no significant difference in symptom perception among middle school, high school, and bachelor or above. Symptom perception of patients with NYHA functional class III and NYHA functional class IV was significantly higher than with NYHA functional class II. Moreover, symptom perception of patients with NYHA functional class IV was 6.723 times higher than with NYHA functional class II , and symptom perception of patients with NYHA functional class III was 4.313 times higher than with NYHA functional class II . The symptom perception of patients with mild depression was significantly higher than that of minimal depression . There was no significant difference in symptom perception between moderate depression and minimal depression, moderate severe depression, and minimal depression.Among the independent variables included in this study, the correlations between symptom perception and LVEF, educational level, NYHA functional class, and depression were statistically significant. The value of LVEF, the level of education, NYHA functional class, and depression were the main independent factors affecting the symptom perception ability of Chinese heart failure patients. Among them, LVEF was an independent risk factor for symptom perception ability. Symptom perception ability might decrease when the value of LVEF increases (B = −0.137, To our knowledge, this is the first study to report the symptom perception in Chinese patients with heart failure. The results of this study support the Theory of Heart Failure Self-Care, Revised and Updated, that, as a key point in self-care, patients’ symptom perception might be conscious or subconscious and is driven by the interactions of the person, problem, and environmental factors. This study found that higher level of depression and the NYHA functional class were independent facilitators of symptom perception in Chinese patients with HF. However, higher level of the LVEF and educational level were independent risk factors of symptom perception ability.The mean HFSPS score in this study was higher than similar studies in the United States and Italy, along with another study that used this scale for a different purpose in China ,33,34,35Chest discomfort. Participants in this study reported a higher level of chest discomfort than those in prior studies [ studies ,30,33. CDyspnea. All patients reported dyspnea-related symptoms and rated themselves at a high level of distress. This finding was consistent with previous studies that also reported high rates and high distress of dyspnea [ dyspnea ,33. Howe dyspnea ,30. MoreSubtle symptoms. Similar results were reported on stomach discomfort, cough, feeling tired, increased girth, needing more rest, and losing appetite [appetite ,30,33,34Edema. Similar to prior studies, less than half of the participants reported tight shoes or weight gain [ght gain ,33,34. HClinical characteristics, including LVEF and NYHA functional class, were independently associated with symptom perception. Similar results had been found, and higher level of NYHA functional class predicted stronger ability of identifying dyspnea-related symptoms ,37. MeanNotably, the only sociodemographic characteristic independently associated with symptom perception was the level of education; patients with primary school/below educational background had a significantly higher symptom perception ability compared with bachelor or above educational background. This might be because participants with bachelor or above educational level were employed and some patients who were highly educated in this study were rehired after their retirement. They may not have had enough time and energy to sense clues of their health conditions . HoweverThe final independent factor predictive of symptom perception was level of depression. It was interesting to note that symptom perception of patients with mild depression was significantly higher than that of minimal depression, presumably because patients with mild depression may be more likely to focus on their inner feelings and changes of the body. Again, findings of other studies vary in this regard. Some studies reported similar findings , whereasThere was no significant relationship found between symptom perception and duration of symptoms, which might be explained by the high rates of cognitive impairment, where cognitive deficits hindered patients’ self-care ability . CognitiThis study is the first study to preliminarily explore symptom perception in Chinese patients with heart failure and expands the understanding of symptom perception influencing factors in HF. The applicability of the Theory of Heart Failure Self-Care has been demonstrated, and it is recommended for use as theoretical guidance for intervention studies and other studies in the future. However, the generalizability of the results of this study is limited due to a moderate sample size with limited diversity in ethnicity and religious affiliation. The nature of the sample should be considered when comparing the results to other populations. In addition, because all the questions in this study were read to the participants by the research investigator where the participants needed to speak out their answers by themselves in the process, the answers might have been given after careful consideration, resulting in subjective evaluation bias of the participants. Finally, as majority of the patients in this sample had cognitive impairment, there might be recall bias.Symptom perception plays an important role in the self-care of patients with heart failure. The symptoms of each heart failure patient might be similar, but the ability to perceive changes in symptoms differs. Understanding what patients with heart failure perceive symptom changes to be can help to build up a better healthcare among this population. This study found that level of depression, the NYHA functional class, the LVEF, and educational status were the independent predictors of symptom perception abilities. At the same time, this study suggests that we might be able to identify patients with poor symptom perception by using these indicators in the future. It helps to clarify whether the patients can perceive the changes of symptoms and to help healthcare providers provide more personalized care and targeting interventions that are more consistent with the patient’s situation.Moreover, this study emphasizes that health policy and healthcare providers should establish closer contact with heart failure patients with depression to help them eliminate these problems. In China, more health policies that focus on patients with heart failure should be developed and implemented. These recommendations are also recommended for use in the health management of community-based patients with heart failure.


Arterial ischemic stroke (AIS) experienced at a young age is undoubtedly a serious medical problem. AIS very rarely occurs at a developmental age, whereas in young adults, it occurs with a higher frequency. The etiologic mechanisms of AIS occurring in childhood and adulthood differ. However, for both age populations, neurological consequences of AIS, including post-stroke seizures, motor disability, and recurrence of the disease, are connected to many years of care, rehabilitation, and treatment. Recurrent stroke was observed to increase the risk of patients’ mortality. One of the confirmed risk factors for recurrent stroke in children is the presence of vasculopathies, especially Moyamoya disease and syndrome, and focal cerebral arteriopathy of childhood (FCA). FCA causes a 5-fold increase in the risk of recurrent stroke in comparison with idiopathic AIS. In turn, young adults with recurrent stroke were found to more often suffer from hypertension, diabetes mellitus, or peripheral artery disease than young patients with first-ever stroke. Some reports also indicate relationships between specific genetic polymorphisms and AIS recurrence in both age groups. The aim of the present literature review was to discuss available data regarding the risk factors for recurrent AIS in children and young adults. Arterial ischemic stroke occurring in children and young adults is a serious medical problem. Taking into account the fact that children and young adults who survive AIS will live longer than older stroke patients, it is important to optimize the medical management for these patients and properly recognize impairments in cognition and mood, because they can be significant barriers in patients’ independent life. The incidence rate for pediatric AIS is about 1.2 to 7.9/100,000 children per year [Most researchers analysing pediatric AIS exclude newborns. Therefore, the age of pediatric patients with AIS ranges from 29 days of life to 18 years ,4,5,6. IThe wide range of stroke incidence in young adults may result from the heterogeneity of individual patient populations, as well as contradictions in defining a person as a “young adult”. The available data may be confusing in terms of this matter. In the literature, a person between the age of 18 and 45 is considered to be a young adult. The upper age limit has been extended to 50 years by some authors ,15. In tThe etiologic mechanisms of AIS occurring in adulthood and at a developmental age differ. Similarity may be found in the case of a significant predominance of the male sex, both in pediatric patients with AIS and in young adults with stroke ,21,22. HDespite this, the neurological consequences of AIS, including post-stroke seizures, motor disability, and recurrence of the disease, are detrimental for both age populations. Additionally, they involve huge costs related to many years of care, rehabilitation, and treatment.According to the latest definition provided by deVeber et al. , recurreThe aim of the present literature review was to discuss and compare the available data regarding the frequency of AIS recurrence in pediatric patients and in groups of young adults, as well as to assess the possible risk factors for recurrent stroke in children and young adults. We also followed data on the secondary prevention of AIS recurrence, both in children and young adults.We searched PubMed, Scopus, and Embase using combinations of the following keywords: “arterial ischemic stroke”, “ischemic stroke”, “stroke”, “recurrent”, “stroke recurrence”, “children”, “pediatric”, and “young adults” (last search early November 2019). As various definitions of “young adults” are available in the literature, we eventually took into account the articles analyzing adult patients younger than 55 years old and pediatric populations aged >one month to ≤18 years. In the present literature review, we included the results analyzing patients suffering from arterial ischemic stroke. For some data on AIS, its recurrence was discussed together with TIA, so we also included the papers. We excluded data on hemorrhagic stroke and cerebral sinuvenous thrombosis (CSVT), as well as perinatal and neonatal stroke. Finally, we discussed the results which we believed were the most interesting or relevant.Stroke and transient ischemic attack (TIA) recurrence occurs in a pediatric population with different frequencies, mainly dependent on the kind and number of AIS risk factors found in the patient ,31. AIS The lowest frequency (2.7%) of recurrent AIS in children was reported by Steinlin et al. , who perIn a study by Fullerton et al. , 42 out On the other hand, in a study performed using an international multicenter stroke database on children with Moyamoya disease, stroke recurrence was 20% over a median follow-up of 13 months, and 9% of patients had multiple recurrences .Summarizing the data on the prevalence of recurrent stroke in children, the studies concerning this problem present groups of children which differ to a great extent in terms of the number of analyzed patients, their age at stroke onset, their ethnicity, the follow-up period, the etiology, and the stroke lesion location (anterior vs. posterior brain circulation), as well as secondary prophylaxis. For these reasons, an analysis of the data is very difficult and clear information on the number of stroke recurrences in pediatric populations remains largely undefined. For a USA population, Kleindorfer et al.  reportedn = 150) within a mean follow-up period of 41.9 months [The prevalence of recurrent stroke in young adults may differ between populations. In a group of 428 patients with first-ever stroke, recruited from 46 hospitals in Baltimore City, five central Maryland counties, and Washington, DC, recurrent AIS was demonstrated in four cases (0.93%) during a study period from 1988 to 1991 . A low f9 months . In a st9 months  was anal9 months . However9 months , based o9 months , who rep9 months . Among E9 months  demonstr9 months . In turn9 months .On the contrary, in Chinese patients with first-ever stroke, an almost two-fold higher frequency of stroke recurrence in comparison to a Finnish study was demonstrated within a mean follow-up period of over five years . SimilarArteriopathy, vasculopathies, and some genetic polymorphisms are among risk factors which may increase the risk of recurrent stroke in children. Since the etiology of AIS is multifactorial, the data also indicate that several risk factors may influence the risk of its recurrence. The study by Lanthier et al.  demonstrAIS recurrence in a pediatric population may be related to the presence of arteriopathies. Focal cerebral arteriopathy of childhood (FCA) has been defined as stenosis revealed by brain vasculature imaging, not related to other specific etiologies, i.e., Moyamoya disease and syndrome, dissection, post-varicella arteriopathy, sickle cell disease, vasculitis, or post-radiation vasculopathy . PreviouFCA causes a 5-fold increase in the risk of recurrent stroke in comparison with idiopathic AIS . The stuIn 2012, CASCADE classification was created to identify, in each AIS pediatric patient at the disease onset, any anatomical abnormality within the brain and neck vessels and the heart . The catIn 2018, British authors from the Great Ormond Street Hospital, London, identified 84 AIS children ; the cases were classified according to the CASCADE criteria and followed for a maximum of four years (mean follow-up period was 2.4 years) . As for Until now, one of the confirmed risk factors for recurrent stroke in children has been the presence of vasculopathy, even when Moyamoya is excluded. In a study by deVeber et al. , AIS recSickle cell disease (SCD) is one of the most common genetic reasons for anemia, mostly present in sub-Saharan Africa, the Middle East, and India and caused by a mutation in the hemoglobin gene (β subunit) in chromosome 11 . SCD affPediatric patients with heart disease are at a high risk of stroke and its recurrence; congenital and acquired cardiological problems are “classical” risk factors for stroke in pediatric populations. In a study by Vazquez Lopez et al. , within In a study by Rodan et al. , which wAccording to an international study by deVeber at al. , the folp = 0.025) [In a 16-year, prospective, national population-based study, i.e., the Canadian Pediatric Ischemic Stroke Registry by deVeber et al.  based on= 0.025) .Recently, several reports indicated relationships between specific genetic polymorphisms and the recurrence of stroke in children. The genetic risk factors, due to the age of the patients, especially pediatric ones, may be of specific importance in the appearance of subsequent AIS. However, studies on the topic are not common and show analyses of various polymorphic variants. Most often, a reliable statistical analysis regarding the relation between a polymorphic variant and stroke recurrence is not possible in pediatric patients due to the fact that recurrent AIS only occurs in a few cases. Therefore, published data on the topic are difficult to interpret and require confirmation based on larger patient populations with AIS.FV) Leiden, FV HR2, or factor II (FII) 20210G>A, among patients with recurrent AIS [HPA 2a/b genotype was over 2-fold higher in cases with recurrent childhood AIS than in cases with nonrecurrent childhood AIS. Additionally, 75% of patients with recurrent stroke had a combined APOE ε2ε3 and ACE I/D genotype, whereas in the pediatric group without recurrent stroke, it was only 6%. In this study, it was also demonstrated that one of the children with recurrent stroke was homozygous for methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism [MTHFR gene was found to be present in the patients who suffered from recurrent stroke, as well as those who had multiple risk factors for AIS [MTHFR gene was proved to increase the risk of AIS in children [MTHFR gene [MTHFR gene was previously linked to a higher level of homocysteine, one of the biochemical risk factors for cerebro- and cardiovascular diseases, both in children and adults.Coen Herak et al. analyzed 73 children with perinatal and childhood stroke and found no polymorphic variants of thrombotic factors, i.e., factor V  were more likely to experience a vascular event compared to subjects with normal fasting glucose . HoweverAmong cases of patients from Estonia suffering from AIS recurrence, diabetes mellitus and peripheral artery disease were observed with a significantly high frequency compared to the group of patients with first stroke . Additionally, Schneider et al.  demonstrAn earlier study by Naess et al.  includinAn analysis based on 121 Chinese patients with Moyamoya disease and first-ever stroke (aged 18–45 years), who underwent revascularization after the acute phase of initial stroke, proved that diabetes is an independent predictor for stroke recurrences (HR 6.76) . Diabeten = 1867), also by Pezzini et al. (24.4% of patients with hypercholesterolemia in a group without recurrence vs. 28.2% in a group with recurrence) [Data on relations between lipid abnormalities and the risk of stroke recurrence in young adults are most often contradictory. In older adults, lipid abnormalities were previously associated with a higher risk of ischemic stroke recurrence in patients with a large-artery atherosclerosis subtype of stroke . In younurrence) .Atherogenic dyslipidemia increased the stroke recurrence risk among stroke patients of the large-artery atherosclerosis subtype (HR 2.79), but not in all stroke patients (HR 1.69) . The meaIn a study by Schneider et al.  in EstonStudies analyzing thrombophilic factors with regard to stroke recurrence are scarce. In the study by Schellekens et al. , no relaCigarette smoking is one of the modifiable risk factors for both primary and secondary stroke prevention in young adults.In young Estonian patients with AIS, the prevalence of smokers was similar between first-ever stroke and recurrent stroke subgroups  . TherefoOne of the most commonly abused drugs in the USA is cocaine. In a study by Cheng et al. , a signiFV gene, and the TT677 genotype of the MTHFR gene) were assessed in relation to the recurrence of ischemic events. The authors observed that the risk of recurrence increased with an increasing number of predisposing genotypes .As for genetic analysis in relation to stroke recurrence in young adults only, the data are poor. The study by Ou et al.  demonstrFV Leiden and the 20210G>A polymorphism in the prothrombin gene, the risk of recurrent deep venous thrombosis after the first episode was significantly increased.Almost 40% of ischemic strokes in adults are cryptogenic and the prevalence of persistent foramen ovale (PFO) is two-fold higher in these patients than in healthy patients. In turn, the most frequent cause of embolism in cryptogenic stroke associated with PFO is deep venous thrombosis. One of the earliest studies analyzing genetic variants in the recurrence of thrombotic events was performed by de Stefano et al. . The autDespite the fact that the results of genetic analyzes regarding the onset of stroke recurrence are inconclusive, these are undoubtedly important data which should be considered in the interaction with other, non-genetic risk factors in estimating the risk of recurrence.Various other predictors for recurrent ischemic stroke have been reported. Previously, Pezzini et al.  demonstrIn turn, among Finnish young adults with stroke, patients with an index stroke caused by high-risk sources of cardioembolism had the highest risk of any subsequent cardiovascular events (HR 3.7), whereas patients with large-artery atherosclerosis had a higher risk of recurrent stroke (HR 2.7) than patients with stroke of an undetermined etiology .In addition, independent predictors for vascular event recurrence in young adults were a familial history of stroke, aPL, and discontinuation of antiplatelet and antihypertensive medications in an Italian population .The proposition of secondary prophylaxis in AIS children was published in 2007 . In the In a study by Stacey et al. , two patPreventive treatment for children with SCD is specific for the disease itself, but also for a particularly high risk of stroke in SCD . In these patients, chronic red cell transfusions and/or hydroxyurea may be administered as alternative therapy; for the first one, serious side-effects  may be the cause of switching to hydroxyurea treatment . DespiteMT-TL1 gene. The first symptoms occur at the age of 2 years and include muscle weakness, a short posture, learning difficulties, migraine and consciousness disturbances, seizures, hearing impairment, and neuropathy of the peripheral nerves, as well as diabetes and cardiomyopathy. In secondary prophylaxis, after the first ischemic episode, to prevent recurrent stroke-like episodes, arginine should be administered at a 150–300 mg/kg/daily oral dose [MELAS  pediatric patients are at a high risk of recurrent stroke-like episodes ; in 80% of patients, the disease is caused by mutation 3243A>G within the ral dose .n = 9) with stroke recurrence took an antiplatelet agent or an anticoagulant agent at therapeutic levels, or both. At the last follow-up, 32% of the patients without stroke recurrence were on acetylsalicylic acid (ASA), 15% were on warfarin, 11% were on low molecular weight heparin, and 39% did not take any antiplatelet or antithrombotic medication. In this group, almost 53% of children with recurrent AIS did not receive effective antithrombotic treatment at the time of recurrence [In a group of 135 Canadian children with AIS and congenital heart disease analyzed by Rodan et al. , 19 paticurrence .Since secondary stroke prevention aims to reduce the risk of subsequent AIS, it is important to know the etiologic mechanism of the initial stroke, as well as accompanying risk factors. Together with antiplatelet or anticoagulant therapy, secondary prevention should include the treatment of vascular risk factors  and/or surgical procedures. However, knowledge on medications used in secondary prevention in young adults is limited. It has therefore been noted that the long-term use of recommended medications raises the greatest problem in preventing secondary stroke, since approximately 30% of stroke patients discontinued one or more drugs within 1 year of hospital discharge .According to the European Stroke Initiative Recommendations for Stroke Management guideline, aspirin should be an antiplatelet drug of first-choice in secondary prevention . In patiIn patients with stroke recurrence, novel oral anticoagulants  can be used for the secondary prevention of cardioembolic stroke, despite appropriate treatment with warfarin . In atheA specific role of statins in young adults with AIS has also been discussed. Their benefit in patients with predominantly nonatherosclerotic stroke etiologies is not clear. Putaala et al.  demonstrUnderstanding the risk factors for the recurrence of arterial ischemic stroke in the young may help to identify the mechanisms of AIS, especially in children, and in some cases, may contribute to disease prevention. Current knowledge on risk factors for recurrent AIS suggests that multiple risk factors may be related to stroke recurrence, both in children and young adults. Risk factors for stroke recurrence differ between child and young adult populations, which is clearly demonstrated in the present literature review. The best documented risk factors for recurrent AIS in children are arteriopathies, especially FCA, which significantly increase the risk of recurrence. A proposal for secondary prevention in children with FCA to avoid subsequent strokes has even been demonstrated. Treatment of a combination of aspirin and corticosteroids allows for the total resolution of vessel wall stenosis in FCA, and, in this way, this therapy may decrease the risk of AIS recurrence. On the other hand, even if antithrombotic medication is used, pediatric AIS recurrence remains a significant problem, especially in children with specific arteriopathy subtypes of the CASCADE classification, i.e., 3A and 3B.Risk factors for recurrent stroke such as diabetes mellitus, hypertension, or lipid abnormalities, have been highlighted in young adults. Undoubtedly, many risk factors, including genetic ones, have an impact on AIS etiology, as well as on the presence of its subsequent consequences, including recurrence. Understanding the links between the presence of a specific risk factor and the occurrence of a post-stroke outcome may be of particular importance for practical reasons. Establishing predictors of stroke recurrence may allow for more effective treatment, and may thus reduce the number of cases.