Separate moderator analyses assessing control group, pathological condition, and MeBI type, highlighted a significantly moderating role of the control group. Indeed, compared to actively controlled studies, studies using a passive control group were associated with a statistically significantly more beneficial impact of the MeBIs (g = 0.83). These results indicate that MeBIs alleviate pathological fatigue and it seems that the studies with a passive control group showed a greater effect of MeBI on the reduction of fatigue compared to studies using active control groups. However, the specific effect of meditation type and pathological condition should be analyzed with more studies, and there remains a need to assess meditation effects on different types of fatigue  and in additional conditions .Persistent fatigue constitutes a prevalent and debilitating symptom in several diseases. The symptom is not effectively alleviated by pharmaceutical treatments, and meditation has been proposed as a non-pharmacological intervention. Indeed, meditation has been shown to reduce inflammatory/immune problems, pain, stress, anxiety and depression which are associated with pathological fatigue. This review synthesizes data from randomized control trials (RCTs) that explored the effect of meditation-based interventions (MeBIs) on fatigue in pathological conditions. Eight databases were searched from inception to April 2020. Thirty-four RCTs met eligibility criteria and covered six conditions (68% cancer), 32 of which were included in the meta-analysis. The main analysis showed an effect in favor of MeBIs compared to control groups ( In the field of neurological and psychiatric disorders, fatigue is typically defined as extreme and persistent mental and/or physical tiredness, weakness or exhaustion . This suFatigue, both mental and physical, is observed transiently in the healthy population, typically due to prolonged periods of demanding activities requiring sustained efficiency, whereas it manifests in a more continuous and severe way in a large number of illnesses . PatholoCurrently there is an absence of convincing evidence for a pharmacological treatment for fatigue . Interveg = –0.37) evidence in favor of mindfulness-based interventions for fatigue reduction. Further, two meta-analyses have evaluated the effect of mindfulness-based interventions on fatigue levels in breast cancer patients , and other pathological conditions in which fatigue is one of the main symptoms, such as cancer, myalgic encephalomyelitis, fibromyalgia, or kidney disease. First, we determined if the effect of a MeBI is larger than the effect of a control group. Then, when data were available, we looked if MeBI differently impacted fatigue regarding the type of MeBI used, the type of fatigue assessed , the pathological condition studied, or the comparator chosen (passive vs active control group).In line with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines , the proConcerning the inclusion criteria, we searched for published and unpublished studies that randomized participants to either a meditation-based intervention or control condition(s). Samples had to comprise adults (mean age ≥ 18 years) with a pathological condition in which fatigue is considered as a debilitating symptom  . The priConcerning the exclusion criteria, we decided not to include studies (i) where the MeBI was delivered in a retreat setting or solely comprised mantras; (ii) only reporting on brain activity or other biological outcomes; (iii) focusing on psychological disorders  or medical conditions where fatigue is not considered as a main complaint associated with the disease .Searches were conducted on eight databases  to identify eligible studies. We also surveyed gray literature . Searches were conducted in April 2020, and articles were independently screened by two reviewers at the title-abstract and full-text stages. Further, the reference lists of articles and reviews were hand searched for eligible studies. Search terms included ‘Meditation’, ‘Mindfulness’, ‘Mindfulness-Based Interventions’, ‘Fatigue’, ‘Fatigue Syndrome’, ‘Chronic’  independently extracted data in pairs from eligible papers using the same template and with a specific coding. The template included: (i) demographic details, (ii) pathological condition, (iii) fatigue type, (iv) intervention related details, and (v) effect sizes. Any disagreements were resolved by consensus.characterized by attentional/emotional regulation and insight practices , (2) Compassion (including loving-kindness) MeBI (related to the ability to develop positive attitudes towards people) administered alone or with the addition of Mindfulness components  Mindfulness interventions mponents , (3) RemConcerning the types of pathological conditions, there were six categories: cancer, multiple sclerosis, myalgic encephalomyelitis, fibromyalgia, acute brain injury , and kidney disease.training.cochrane.org/resource/grade-handbook).Two reviewers independently assessed the risk of bias and integrity of the randomization processes using the Cochrane risk of bias tool version 2  and the g ≤ 0.32 corresponds to a small effect size, 0.33 ≤ g ≤ 0.55 to a medium effect size, and g ≥ 0.56 to a large effect size.Our strategy was to calculate the meta-analysis scores by comparing effect sizes within and between studies. We used Hedges’ Standardized Mean Difference and ran a random-effect meta-analysis using the default restricted maximum likelihood as estimator . For outFor the meta-regression, we report models using the Hartung-Knapp method . The firFor the subgroup analyses, we looked in each modality of the different moderators if there was a significant difference between meditation-based interventions and control groups. In the first subgroup analysis, we separately evaluated actively controlled and passively controlled studies. We next calculated pooled effect sizes for each type of MeBI. Finally, we analyzed the effect of MeBI for each type of pathological condition separately.2, which represents the variance between the studies, and I2 , which refers to the proportion of observed dispersion due to real variation in effect sizes, rather than random error. R version 3.4.4  was used to perform all analyses.For heterogeneity concerning meta-analysis and subgroups analyses, we evaluated two parameters: tauk = 2746), 4108 studies remained. Following title and abstract screening, 4057 studies were excluded. Through the full-text screening of the 51 remaining records, we excluded 17 studies. The kappa index for the whole screening was .94. This resulted in a final total of 34 studies meeting the eligibility criteria (The literature search (inception to April 2020) yielded 6854 records; after the removal of duplicates . Six studies took place in the United Kingdom (18%); two studies in Italy (6%), Korea (6%), Netherlands (6%), and Canada (6%); and one study in China (3%), Turkey (3%), Japan (3%), Switzerland (3%), and Sweden (3%).Our selection process resulted in a total of 34 studies. Publication year ranged from 2000 to 2020 (median: 2016). The majority of studies took place in the United States . There was a high proportion of women (84.61%), which can partially be explained by some studies focusing on breast cancer in women.k = 23) was the main topic, followed by multiple sclerosis (k = 6). Other pathologies included myalgic encephalomyelitis (k = 2), fibromyalgia (k = 1), acute brain injury (k = 1), and kidney disease (k = 1).Among various pathologies, cancer . As detailed in Supplemental Table 1, some questionnaires assessed a general fatigue state with one or several questions, while others distinguished between mental and physical fatigue . Only one study used a mental fatigue scale . Most of the studies used mindfulness-based interventions. More specifically, 18 studies used Mindfulness-based reduction interventions or derivative forms of this intervention. Seven studies used Compassion interventions or Mindfulness and Compassion interventions; more specifically, one study used a compassion intervention only  and had a median of eight meditation sessions . The duration of each session had a median of 120 minutes . Adherence data have not been reported due to the limited amount of data available and the great variability in the way they were reported between studies. For example, six studies reported percentages of people practicing at home without providing duration of practice and ten provided an average of the number of minutes spent by people to do some exercises at home.The included studies  featuredion only . Six stuAmong the 34 studies, ten (29%) had an active control group and 24 (71%) had a passive control group. Four of the ten studies with an active control group had more than one control group. Three studies (9%) had an active control group and a passive control group, and one study (3%) had two active control groups. The control interventions in the nine actively controlled studies used in the meta-analysis were: Ambulant Activity Feedback therapy, Health Education, Music, Multiple Sclerosis Education, Progressive Muscle Relaxation procedure, Psycho-Educational Intervention, Telephone-Based Support Group, Online psychoeducation treatment, Psychoeducation and support. For the 23 passively controlled studies used in the meta-analysis, 17 (74%) used a waitlist and six (26%) utilized usual care.Supplemental Table 3 for a detailed presentation).Of the 34 studies included, 26 (76%) reported a significant decrease of fatigue symptoms immediately after the intervention. Of these 26 studies, three showed that the effect is superior to the effect of another active intervention and 18 showed a superiority effect by comparison to passive control. The five remaining studies showed no differences between MeBI and a control group (one passive and four active). Sixteen studies with a positive immediate effect of MeBI reported long-term follow-up (from 10 to 64 weeks after the end of the intervention). From these studies, the positive effect of MeBI was maintained at long-term for nine studies (56%). More precisely, the maintenance of the effect was superior to the one in the passive control groups in seven studies out of the nine and for two, MeBI did not show a better maintenance than control group at follow-up (see The risk of bias assessment of 34 studies is summarized according to the five domains of the assessment tool .k = 21), some were judged to have some concerns , and the remainder were considered to be at high risk of bias .Concerning the first domain of ‘Randomization process’, the majority of studies were judged to be at low risk of bias . The remaining studies were considered to have some concerns .For the second domain, ‘Deviations from intended interventions’, the majority of studies were judged to be at low risk of bias , with the remaining studies considered to be at high risk .Related to the third domain (‘Missing outcome data’), the majority of studies were judged to be at low risk of bias . The remaining studies were considered to be at high risk .For the fourth domain (‘Measurement of the outcome’), the majority of studies were judged to be at low risk of bias , some concerns  and low risk of bias .Finally, concerning the fifth domain: ‘Selection of the reported result’, the studies were judged with high risk of bias , the median of some concerns rates was 5.9% (0 to 67.6%), and the median of high risk rates was 5.9% (0% to 85.3%).a) Meta-regressions on all studiesFor the meta-analysis, two studies were not included because data were not available to calculate the effect sizes . In the Moreover, for four studies, two measures of fatigue were available. For Kim et al. , we chosg = 0.62, I2 = 91.51%).First, we conducted a meta-analysis without any moderator specified in the model . The modg = 0.83; CI = ) compared to studies with an active control group . However, this was not the case for pathology or MeBI moderators (ps > .05).Then, we used three moderators for meta-regressions: type of control group , type of MeBI , and pathological condition  to better understand the effect of the MeBI intervention on fatigue. These moderators were examined in separate models . When th; CI = 0.2, 1.43) The forest plot of the different studies and their standardized mean differences are presented in b) Exploratory analysesWe performed subgroup analyses to assess specifically the effect of each moderator . However, for actively controlled studies, the between group difference was not significant .We first measured the impact of MeBI on fatigue in studies that used a passive control group and those using an active control group. For passively controlled studies, MeBI outperformed comparators with a large effect size . However, we did not find an effect for compassion interventions or mindfulness-based and compassion interventions , or for interventions delivered remotely . Concerning ‘other’ MeBIs (k = 3), there are not enough studies (df < 4) to consider the results as reliable.Next, we investigated the impact of different MeBI types on fatigue. There was a significant effect of mindfulness-based interventions with a large effect size , while a small effect size was observed for multiple sclerosis .For the impact of MeBI on fatigue in different pathological conditions, a positive effect of MeBI on fatigue with a large effect size was observed for cancer pathology (df < 4) to consider the results as reliable.Concerning fibromyalgia (k = 2), myalgic encephalomyelitis (k = 1), kidney diseases (k = 1), acute brain injury , there are not enough studies , df < 4 c) Sensitivity analysesSupplemental Table 4). Concerning the subgroup analyses, we still observe a higher reduction of fatigue for MeBI compared to passive control groups, a higher reduction in the Mindfulness group and also for people that had cancer or multiple sclerosis . However, there is now also a significant effect of MeBI by comparison with active control groups.The publication bias analysis cannot be assessed as we did not find unpublished studies on the topic. Due to a high heterogeneity between studies, supplementary analyses were performed without outliers . The meta-analysis without moderator remains significant. For the meta-regression, we obtain similar results with the 26 remaining studies: a significant effect of the type of control group but not of the type of MeBI or the type of pathology formal support provided by all kind of interventions and their benefits on quality of life . An alteRegarding publication bias, only five studies on meditation and fatigue were reported on OpenGrey, three on healthy people, one was qualitative study, and one was preliminary results presented in a doctoral dissertation and published later . This coRegarding the intervention moderator, the mindfulness interventions appear to be interesting to use for the alleviation of fatigue symptoms. Due to the higher number of studies on the topic, we also looked at subgroups as exploratory analyses , but theRegarding the moderator of pathological condition, MeBI seems to have a strong impact on fatigue related to cancer. Again, the number of studies being higher for this population, we decided to look at subgroup analyses  and we fFrom a theoretical viewpoint, mental and physical fatigue are considered as distinct entities , with thTo sum up, our systematic review and meta-analysis shows a positive effect of MeBIs on fatigue in pathological conditions. Exploratory analyses showed that mindfulness MeBI seems the most helpful, particularly in cancer and multiple sclerosis patients. This confirms the results of three previous recent systematic reviews on cancer . Howeverk = 2) on fatigue to an active control group. Further studies are necessary to determine if the effect of MeBI is driven by fatigue level.A still-open question is how the intensity of the fatigue could affect MeBI efficacy. Some studies therefore used a specific level of fatigue in their inclusion criteria. For example, Johns et al.  showed aFinally, our review gathered articles employing a subjective assessment of fatigue. A recent meta-analysis showed a beneficial effect of MeBIs on objective measures of cognition . Future The major strength of this systematic review and meta-analysis is that we included considerably more studies with different pathological conditions than in previous publications. Eight databases were searched for unpublished studies and we finally included 34 studies yielding the most comprehensive review of MeBIs on fatigue in pathological conditions. Meta-regressions were done on 32 studies, three moderators were used and exploratory subgroups analyses were also run. Therefore, the current results are likely to be more reliable, especially concerning the meta-analysis. We also included more pathological conditions across which effects could be contrasted, and compared several types of MeBI as well.First, there is a lack of homogeneity among fatigue-related data. Indeed, 16 different scales were administered among the included studies. The three components of pathological fatigue  are incAs mentioned previously, fatigue is highly debilitating in various pathologies. Because of its severity and frequency, it is crucial to consider and try to mitigate this state. Fatigue is typically not effectively treated using pharmacological interventions. A potential useful non-pharmacological approach could thus be MeBI.Alleviating the symptoms of fatigue will positively affect everyday life among people with pathological conditions. Indeed, different studies have shown that fatigue can interfere with work, activities and social life . TherefoThis study aimed to identify the impact of MeBIs on fatigue in pathological conditions. We showed that people who followed a MeBI experienced a greater reduction in fatigue symptoms compared to passive control groups. However, the change in levels of fatigue did not differ between meditation and active control groups. It seems particularly relevant to use MeBIs to cope with fatigue in cancer and multiple sclerosis. The studies about other pathological conditions are scarce, making it difficult to reach conclusions. Further studies are needed to more comprehensively evaluate the impact of various types of MeBI on various pathologies associated with debilitating fatigue.The additional file for this article can be found as follows:10.5334/pb.1182.s1Supplemental Material.Information about study design , follow-up data as well analysis without outliers can be retrieved in Supplemental Material.


Introduction: Schizophrenia is characterized by psychotic symptoms such as delusions, hallucinations, and disorganized thinking and speech. Patients suffering from schizophrenia incited by these delusions react violently in response to real or imagined threats; this engages them in violent behaviours and thus poses a threat. Sparse data are available for patients from India with regard to schizophrenia patients acting on their delusions. The aim of this study was to assess the prevalence of delusional action in patients suffering from schizophrenia and to identify the phenomenological characteristics of those delusions which are associated with action.Material methods: This study was conducted on patients with a diagnosis of schizophrenia admitted to the indoor patient department (IPD) of the Department of Psychiatry, K.D. Medical College, Hospital & Research Centre, Mathura, India, during the period of February 2022 to July 2022. A semi-structured, semi-open-ended questionnaire was used for interviewing patients regarding demographics, the course of illness, past medical illness, the family history of psychiatric disturbances, and substance use. The study tool used for delusion was the Maudsley Assessment of Delusions Schedule (MADS).Results: Out of 56 selected subjects, 34 acted on delusion and out of these, 19 were male and 15 female. In our study gender did not play any significant role in acting on delusion. Literacy and nuclear living households played a significant role in influencing delusion-driven behaviours, while the distinction between urban and rural living, though noteworthy, fell just short of achieving statistical significance. An emotional state like anger was significantly important to the patient’s acting on delusion, which led to violent behaviour or self-harm.Conclusion: Positive responses are more likely to be associated with leading action on delusion as compared to negative responses, which were also associated with action on delusion; for example, anger was significantly important in the patient’s acting on delusion, which led to violent behaviour or self-harm. Schizophrenia is a complex and chronic mental disorder that affects a person's thinking, perception, emotions, and behaviour, characterized by a combination of symptoms, including hallucinations, delusions, disorganized thinking and speech, social withdrawal, diminished emotional expression, and cognitive impairments . SchizopThe genetic element plays a highly significant role in the development of schizophrenia. Higher risk is associated with people having first-degree relatives  with schizophrenia. Multiple genes are believed to play a role, in the development of schizophrenia. Various environmental factors can contribute to the risk of developing schizophrenia. These include prenatal and perinatal factors such as maternal infections during pregnancy, complications during childbirth, prenatal malnutrition, and exposure to certain toxins or substances. Increased risk of schizophrenia is also associated with growing up in urban areas, social adversity, migration, and exposure to childhood trauma or abuse .Acting on these delusions poses a unique challenge for patients, caregivers, and healthcare professionals ,5. ActinThis is an observational cross-sectional of patients diagnosed with schizophrenia admitted to the indoor patient department (IPD) of the Department of Psychiatry, K.D. Medical College, Hospital & Research Centre, Mathura, India, during the period of February 2022 to July 2022. The selection was done based on the pre-decided inclusion and exclusion criteria. Patients aged between 18 to 65 years with at least one mood incongruent delusion were included in the study. Patients who refused to give consent, had severe formal thought disorders, and with co-morbid psychiatric illness and mental retardation were excluded from the study. The study was approved by the Institutional Ethics Committee of K.D. Medical College, Hospital & Research Centre (vide letter KDMCHRC/IEC/2022/01). Written informed consent was taken from all the participants.A total of 72 subjects were examined. Of them, 56 were included in the study based on the selection criteria, including 30 males and 26 females. Diagnosis of schizophrenia was done based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM 5) [Based on the above tools, a semi-structured, semi-open-ended questionnaire was used for interviewing the patient regarding demographics, the course of illness, past medical illness, the family history of psychiatric disturbances, substance history and mental status examination. Statistical analysis was carried out using Python 3.10.0 software . Statistical associations were tested using χ2 test. Significance was set at p<0.05.Out of these 56, there were 32 males 57.14%) and 24 females (42.85%)  . InteresIn our demographic analysis, we observed that the male-to-female ratio did not show statistical significance concerning the presence or absence of actions driven by delusions. Despite the higher prevalence of schizophrenia in males compared to females, our findings suggest that once individuals are diagnosed, gender does not appear to exert an influence on their behaviour . Our resWe found that more than 22.7% of non-acting subjects were more elated or happy with their beliefs as compared to a measly 8.8% of participants who acted out on their delusions. Also, anger was seen to be higher in the non-acting group as compared to the group that acted on delusion, which was the only significant trait of all the emotions. According to the research conducted by Patoilo on individuals with intermittent explosive disorder (IED), they similarly identified anger as one of the most frequently provoked characteristics . Our resTypes of delusion associated with action specifically positive were significantly higher in our study, which was in accordance with Patel et al., although as per Buchanan et al., they did not reach a significant level and non-action was more as compared to action on certain beliefs ,13. In oOf the participants who acted on delusions, 64.7% self-reported that delusions made them lose their temper while only 40.9% of participants who did not act on delusions self-reported it; based on reports by informants, 14.7% of the former group were violent on one or more occasions. Coid and Ullirich stated that most of the subjects who acted in violence were in a delusion of persecution, which made them angry, which is a warning sign of violent behaviour ,17.A total of 51.78% of subjects from our study talked to someone about their delusions; 55.88% of the subjects acting on delusion talked to some and 44.45% of non-acting participants talked to someone but the comparison of both groups was statistically insignificant. Our results tally with most of the studies found in the literature ,12,18. SOf subjects who acted on delusions, 26.4% tried to leave the house or move out but none reported the same in the other group; this was again statistically significant with a p-value of 0.015. These results are in unison with the systematic review of safety-seeking behaviour and acting on delusions conducted by Tully et al. . In relaWithin the group that acted on delusions, a mere 8.82% of participants reported instances of self-harm, and these individuals exhibited some degree of insight into their actions. Conversely, self-harm was absent in the other group, although statistical significance was not achieved, possibly owing to the limited sample size. Notably, a separate study from India reported a higher self-harm risk of 22.6% . Our stuWe did not find the level of insight to predict acting on delusions, which differs from the study conducted by Patel et al. and Buchanan et al. ,13. Of oLimitation of studyThe study's limitations include a relatively small sample size and its exclusive location in an urban setting, which predominantly featured literate individuals from middle-class backgrounds, potentially biasing the results. Additionally, the cross-sectional nature of the study inherently constrains its overall potential for drawing comprehensive conclusions.Acting on delusions does not have any gender bias. Emotional states such as fear, anxiety, and depression are more likely to result in acting on delusion. Literacy and nuclear living have a significant role in leading to actions on delusion. We also conclude that positive responses are more likely to be associated with leading action on delusion as compared to negative responses and the delusion of persecution was the most common delusion in our study, which was also associated with action on delusion.


Immune thrombocytopenia (ITP) is an autoimmune disease characterized by isolated thrombocytopenia. Recently, the pathophysiology and novel drugs of ITP have been the focus of researchers with plenty of publications emerging. Bibliometrics is the process of extracting measurable data through statistical analysis of published research studies to provide an insight into the trends and hotspots.This study aimed to provide an insight into developing trends and hotspots in the field of ITP by bibliometric analysis.By using three bibliometric mapping tools , we summarized the overview information of retrieved publications, as well as the analysis of keyword co-occurrence and reference co-citation.A total of 3299 publications with 78066 citations on ITP research were included in the analysis. The keyword co-occurrence network identified 4 clusters relating to the diagnosis, pathophysiology, and treatment of ITP respectively. Then the reference co-citation analysis produced 12 clusters with a well-structured and highly credible clustering model, and they can be divided into 5 trends: second-line treatment, chronic ITP, novel therapy and pathogenesis, COVID-19 vaccine. Treg cells, spleen tyrosine kinase, and mesenchymal stem cells were the latest hotspots with strong burstness.This bibliometric analysis provided a comprehensive insight into research hotspots and trends on ITP, which would enrich the review of the ITP research. Patients may be asymptomatic at presentation, or they may present with mild mucocutaneous or life-threatening bleeding . The patThe rapid progress and development of medical science in recent years have led to an exponential growth of academic papers every year, resulting in so-called information overload or filtering failure . Scholar2in vivo and in vitro experiments exploring the pathology and mechanisms of ITP) and clinical papers .The data used in this study were retrieved from the Web of Science Core Collection database (WoSCC) on October 16, 2022. The search keyword query was: TI= “Idiopathic Thrombocytopenic Purpura*” OR “Immune Thrombocytopenic Purpura*” OR “Immune Thrombocytopenia*” OR “Werlhof* Disease” OR “Autoimmune Thrombocytopenia*” OR “Autoimmune Thrombocytopenic Purpura*” OR ITP. The database source was limited to the Web of Science Citation Index Expanded (SCI-Expanded) with a publication date from January 1, 1999, to October 16, 2022. Original articles and reviews were included as document types since they can represent the current status of research in a field , 11. The2 or more citations (http://www.VOSviewer.com/) was used to analyze the co-occurrence of keywords and co-authorship between countries/regions. The networks of co-cited references and the burstness of keywords were analyzed by CiteSpace (http://cluster.ischool.drexel.edu/~cchen/citespace/).Many bibliometric mapping software tools have been created and used by scholars. In this study, we chose the widely used tools for the analysis . For desitations , 15. Botitations   “hematology” category. Meanwhile, references cited in the documents were mainly from the two journals. The top ten productive and locally cited sources were shown in We also analyzed the main institutions and sources implicated in the field. As shown in 3.3Author keywords, an essential part of an article given by the authors, can represent the research topic of a publication. To explore the research trends and hotspots, 279 out of 2610 keywords with a frequency of 5 and above were extracted for the co-occurrence analysis in VOSviewer. The 60 most frequently occurring keywords were shown in We plotted the overlay visualization for the co-occurring author keyword network to analyze the trends of the study. The color of an item was determined by the average publication year, where colors ranged from blue (earlier) to green and yellow (latest). It showed that keywords such as “COVID-19,” “avatrombopag,” and “tyrosine kinase” were newly emerging research topics. “Th17 cell,” “TPO-RAs,” and “autophagy” were hotspots in latest five years. In addition, the analysis of burstness . Many patients received surgery and achieved remission . In the Helicobacter pylori infection. Approximately 25% to 30% of adult patients developed cITP that was refractory to corticosteroids and splenectomy and other available treatments  for better visualization. Furthermore, the bibliometric outcomes of this study included citation, co-citation, and co-occurrence, and different types of visualization mapping were drew to comprehensively elucidate the research field. We studied multiple bibliometric indicators , temporal metrics, such as citation burstness, and structural metrics, such as betweenness centrality.This bibliometric analysis provided a comprehensive insight into research hotspots and trends on ITP. Both publications and citations have witnessed a steady increase over the decades. USA, China, and Japan were the countries that studied ITP most and worked closely with each other. In the further analysis of 3299 publications, the research on pathophysiology and treatment of ITP was identified as the research hotspot, such as TPO-RAs, T cell subsets, etc. In addition, COVID-2019, Syk, and MSCs were emerging hot issues. Therefore, this study can help researchers better explore the development and trends of this field.The original contributions presented in the study are included in the article/FW: Formal analysis and writing-original draft. CL: Data curation and validation. JM: Software and methodology. JZ and YW: Conceptualization. CW: Reviewing and editing, supervision. All authors contributed to the article and approved the submitted version.


Thus, the authors aimed to assess the safety and efficacy of the Ozaki technique in treating aortic valve diseases.In 2014, Ozaki A comprehensive search was performed via PubMed, the Cochrane Library, Scopus, and the Web of Science up to 20 February 2022. Random-effects meta-analysis models were employed to estimate the pooled mean and SD or event to the total of the Ozaki procedure. Relevant records were retrieved and analyzed by OpenMeta analyst software.P<0.001), mean aortic cross-clamp time of 112.46 mins , reoperation with a low risk of 0.011 , conversion to aortic valve replacement with a low risk of 0.004 , finally ICU stay (days) and hospital length of stay (days) with a mean of 2.061 days  and 8.159 days , respectively.A total of 2863 patients from 21 studies were finally included in our analysis. Ac. Ozaki technique showed statistical significance in terms of mean cardiopulmonary bypass time of 148 mins (95% CI 144–152.2, The Ozaki procedure provides a safe surgical technique with low mean cardiopulmonary bypass time and aortic cross-clamp time; moreover, a mean of 2-day-postoperative hospital stay was observed with the Ozaki procedure with a low risk of conversion to aortic valve replacement, reoperation, ICU and hospital stay, and death. Highlightset al. in 2014.The Ozaki procedure was first introduced by Ozaki The Ozaki procedure is a new surgical approach for aortic valve replacement.Our meta-analysis highlights the safety of the Ozaki procedure in terms of its low cardiopulmonary bypass time and aortic cross-clamp times.The Ozaki procedure has a mean of 2 days hospital stay postoperatively, which is the lowest compared to other known valve replacement modalities.Ozaki has a low risk of both aortic valve reoperation and conversion to aortic valve replacement.2. On the other hand, AR decreases with age with a prevalence of 4.9%, which is increasing with age until the sixth decade when incidence decreases, yet the percentages may be underestimated due to the AS-associated degree of AR3.Being the main affected valve in the human heart, aortic valve diseases constitute a large public health burden. Aortic valve diseases are either aortic stenosis (AS) or regurgitation (AR), which both have detrimental effects on the cardiac muscle and systemic circulation. AS is evident in the elderly population and its incidence increases with age to a prevalence of 9.8% of the population in the eighth causing a variety of clinical manifestations such as left ventricular hypertrophy, decrease cardiac output, and heart failure4. The gold standard in treating aortic valve disease is AVR using another valve with the firstly introduced mechanical valves (MV), then biological or prosthetic valves5. Both have their advantages and disadvantages with favor biological valves due to no need for hazardous anticoagulants and more durability. Nevertheless, biological valves are synthesized from bovine or pig pericardium, which causes an unavoidable state of chronic autoimmune inflammatory response that may lead to degeneration and valve replacement5. Therefore, in 2014, Ozaki et al.6 introduced a new surgical technique which is neo-cuspidation; forming a new valve from the pericardium decreasing the risk of inflammation and rejection. Thus, we aimed in our systematic review and meta-analysis to further assess the safety and efficacy of the Ozaki technique in treating aortic valve diseases.Treatment of valvular heart disease accounts for 10–20% of all cardiac surgical procedures performed in the USA, with aortic valve replacement (AVR) accounting for around two-thirds of all heart valve surgeries8. Our meta-analysis was registered on the research registry with an identification number: researchregistry9010.The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline and Cochrane handbook were fulfilled in this systematic review and meta-analysisWe searched PubMed, the Cochrane Library, Scopus, and the Web of Science for studies that investigate the usage of the Ozaki procedure for patients who need AVR up to 20 October 2022. The following search terms were used:  AND ); moreover, reviewing the reference lists of retrieved articles were used to complement the broad search.Studies that investigate the usage of the Ozaki procedure for AVR and articles that were published in peer-reviewed international journals and had enough data for qualitative and quantitative analysis were included with no language restriction. We excluded conference papers, unpublished articles, letters to the editor, posters, and animal studies.We extracted the following data from the included studies as baseline characteristics: name of the First author, publication year, country, study design, sex, mean age, total sample size, BMI, BSA, cardiovascular risk factors, aortic valve pathology, and aortic valve anatomy  Table . Further9. The domains of NOS include three domains for selection, comparability, and outcomes: Representativeness of the Exposed Cohort, Selection of the Non-Exposed Cohort, Ascertainment of Exposure, Demonstration that Outcome of Interest Was Not Present at Start of Study, Comparability of Cohorts based on the Design or Analysis, Assessment of Outcome, Was Follow-Up Long Enough for Outcomes to Occur, and Adequacy of Follow-Up of Cohorts. Two independent reviewers (R.A.F and M.S.A) screened the methodological quality of the included studies, and in the case of discrepancies, they were resolved by a senior author. Moreover, the work has been outlined in accordance with AMSTAR  Guidelines10, Supplemental Digital Content 1, http://links.lww.com/MS9/A174.We used the Newcastle–Ottawa Scale (NOS) to assess observational studies11. Random-effects meta-analysis models were employed to estimate the pooled mean and SD or event to the total in the form of risk (R) in the Ozaki procedure. A P-value less than 0.05 was considered statistically significant. The data was continuous, we used the mean and risk with a 95% CI to assess the estimated effect measure. Moreover, heterogeneity was evaluated using the inconsistency (I2) and χ2 tests. I2>50% was considered substantial heterogeneity in the studies. If substantial heterogeneity was found, a leave-one-out meta-analysis was performed to show how each study affects the overall estimate by excluding one study interchangeably at a time from the meta-analysis.We conducted a single-arm meta-analysis using OpenMeta analyst softwarehttp://links.lww.com/MS9/A175). Nine studies were retrospective cohorts, 11 were prospective cohorts, and one was case report.Our search strategy resulted in a total number of 1525 studies. After the title and abstract screening and removing the duplicates, 33 full-text articles were evaluated for eligibility. According to the PRISMA checklist, we performed the full-text screening with 21 papers met our criteria and were included in our meta-analysis , Our study included 2863 participants of which 1212 patients were males. AS was the indication of AVR in 979 patients, while AR was in 499 patients with the rest being either unknown or a mix of both. The mean BMI is 25.24 and the mean BSA is 1.5. The baseline characteristics are illustrated in Table 5.8, Our http://links.lww.com/MS9/A176). Furthermore, according to AMSTAR-2 guidelines, our study was compliant with the guidelines and scored high confidence of evidence according to the checklist .For our included observational studies  studies, judged by following NOS guidelines, 14 were of good quality and 6 were of fair quality mostly due to the nonmatching of the cases and controls regarding the confounders and lack of selection of controls as shown in   . Regarding conversion to AVR, an analysis including studies showed a low risk of conversion from the Ozaki procedure as risk 0.004   included 18 studies, in which the Ozaki procedure showed a statistically significant pooled mean of 148 min  Fig. . FurtherP<0.001, I2=93%) and 8.159 days , respectively. Moreover, the analysis of the mean and peak aortic valve pressure gradient (mmHg) showed a pooled mean of 11.521  and 15.420 , respectively   and hospital length of stay (days) with the Ozaki operation, which showed a statistically significant pooled mean of 2.061 days , (I2=99%), (I2=93%), (I2=97%), (I2=98%), and (I2=99%), respectively, the leave-one-out analyses revealed that there were no single study effects on the overall effect size . However, Ngo 2020 in the ICU stay analysis was revealed to affect the overall effect size .Despite the significant heterogeneity that was observed in CPBT, cross-clamp time, ICU stay, hospital stay analyses, mean, and peak pressure gradient,  with Ozaki operation showed a statistically significant pooled mean of 2.061 days, and the mean and peak aortic valve pressure gradient (mmHg) showed a pooled mean of 11.521 and 15.420, respectively. We also observed a significantly decreased risk of death with the Ozaki procedure with a pooled risk of 0.015.et al. reported that about 20% of patients undergoing AVR develop atrial fibrillation during the period of follow-up, rendering them prone to using anticoagulants irrespective of the type of valve transplanted12.Recently, it has been a dilemma to choose between MV prosthesis and bioprosthetic valves (BV). This dilemma arises from the need for the long-term use of anticoagulants for the MVs group and therefore the increased risk of bleeding, especially in the elderly group. On the other hand, the bioprosthetic valve, although not needing anticoagulants, has an increased risk of reoperation due to its low durability. However, the incidence of bleeding after both types is another conflict. A recent study by Tosello 13. A similar SR done by Tasoudis et al. showed that mortality risk from either BVs or MVs differs according to age category. BVs show increased mortality risk in patients aged 50–70 years while they have a better survival rate in patients aged greater than 70 years and no difference between both types in patients less than 50 years14. Because of this dilemma, multiple studies were conducted and, consequently, the guidelines have been a dynamic change. From 2007 to 2017, ESC guidelines for valvular heart disease lowered the age limit recommended for MVs to less than 60 years for the aortic position based on type C evidence15. Clinical practice has shown another decrease in this age limit, showing that most patients aged between 50 and 69 years preferred the BVs, resulting in a wide age range using BVs18.In Leviner’s meta-analysis, which compared MV replacement versus bioprosthetic ones in 16 876 patients, they showed that BVs are associated with increased mortality risk by 22%, increased reoperation risk by 202%, and a 42% risk reduction of bleeding19. The introduction of minimally invasive procedures such as valve-in-valve transcatheter aortic valve replacement (ViV TAVR)20. Recently, ViV TAVR is an alternative to resurgical aortic valve replacement for patients with bioprosthetic valve degeneration; it is a less invasive procedure that has more favorable outcomes than resurgical aortic valve replacement as the second operation is associated with increased surgical risk22. Bruno et al. showed that ViV TAVR has better short-term outcomes as regards major bleeding, new-onset AF, and length of hospital stay. However, there is no significant difference between both groups in the mid-term follow-up23.The increased age range for BVs usage in the current era may be attributed to different factors, including the illusion perceived by the patients that BVs are better than MVs as the bleeding outcome after MV transplantation is early witnessed postoperatively affecting the lifestyle of patients, while the main concern of BVs, which is reoperation is witnessed later28. However, there are some concerns regarding it such as fear of failure, especially if there was AI and potential dilatation of the graft that results from mechanical adaptation phenomena which are called ‘elastic fiber fragmentation’29. There are multiple generations of xeno-grafts including Trifecta, the Carpentier-Edwards Magna Ease, Mitroflow, Sorin’s Freedom Solo, and Freestyle. Those xeno-grafts are bovine pericardial bioprostheses that have the advantage of their fast application and they mimic the natural valve. On the other hand, the xeno-grafts have the risk of structural valve deterioration31, and they need aortic annulus enlargement due to their large size32. Many studies compared the subtypes of xeno-grafts with each other36.According to the previously mentioned, studies discussing the pros and cons of bioprostheses are crucial. There are different types of bioprostheses including pericardial valves either autologous or xeno-grafts and pulmonary autografts (Ross procedure). The Ross procedure is considered the gold standard in children and young adults due to its good hemodynamic performance and growth potentialet al.40; that they used the autologous pericardium in augmentation of the native valve and thus increasing the coaptation zone after treatment of the pericardium with glutaraldehyde solution. This solution increases the resistance of the valves against degeneration and preserves their pliability. Another way of AVNeo using the autologous pericardium was prescribed by Halees et al.41; they replaced the three aortic valves with a single pericardial strip. Ozaki et al. came up with a new technique in which they made up separate pericardial leaflets for each coronary cusp. Ozaki et al.42 showed that their technique is especially effective in the treatment of calcified AS and in patients with small aortic annulus.Aortic Valve Neo-cuspidization (AVNeo) is the usage of the autologous pericardium in AVR. It has an advantage over the other BVs that it has better hemodynamics and a lower trans-valvular gradient. It was first reported by Duran et al.43 as regards the AVNeo procedure. Benedetto et al. discussed the xeno-grafts and autologous pericardial grafts. However, we handled the Ozaki technique conclusively in a more comprehensive way; we included 22 studies with 2863 patients in contrast to 8 studies with a total number of patients equal to 1259 in Benedetto’s SR. Nevertheless, the AVNeo procedure in general and specifically the Ozaki technique is a substantial research question that lacks steady evidence and needs to be targeted by further comparative and randomized clinical trials in the future as most currently available evidence is just observational and single-arm studies.To the best of our knowledge, our systematic review and meta-analysis is the most comprehensive one to date discussing the Ozaki technique in AVR. There is only one SR and meta-analysis that was done by Benedetto Our study is the largest to further assess the effectiveness of such a newly proposed surgical technique, yet our main limitations come from the observational nature of all our included studies, besides the absence of a certain comparator in nearly all the included studies, thus, we conducted a single-arm meta-analysis which is not considered as powerful as double-arm. Although there was heterogeneity found in some of our outcomes, it was solved using sensitivity analysis and leave on out analysis to ensure the robustness of our analysis and explore the effect of each study separately, which showed no study affecting the pooled effect estimate. Moreover, our heterogeneity can be raised from the disparity in the baseline characteristics of operated patients as Ozaki is not secured for a specific population yet most of centers it is merely based on surgeons’ decision and whether other procedures are possible, with both the novelty and complexity of such a surgical technique making the surgical expertise as well a key role in the outcomes of each study.To conclude, the Ozaki procedure provides a safe surgical technique with less mean CPBT and mean ACCT. Associated with a small mean postoperative hospital stay of 2 days, the Ozaki procedure has been associated with a low risk not only of reoperation but also of conversion to other AVR modalities or reoperation.Our research is systemic review and meta-analysis. As a general rule, systematic reviews do not typically require ethical approval since they do not involve direct contact with human subjects.Not applicable.No funding was received.A.K.A., M.S.A., E.R.G., and R.A.F. performed the screening and data extraction; A.K.A did the analysis; M.S.A., R.A.F., and E.R.G. wrote the primary draft, which was further edited, modified, and reviewed by A.K.A., R.A.F., and A.S.H. All authors reviewed and agreed to the final version of the manuscript. All the authors gave final approval of the version to be submitted.The authors declare that there is no conflicts of interest.Name of the registry: not applicable.Unique Identifying number or registration ID: not applicable.Hyperlink to your specific registration (must be publicly accessible and will be checked): not applicable.All data and figures are included in the manuscript and the supplementary data.Not commissioned, externally peer-reviewed.Not applicable.


This study aimed to study the relationships between emotional regulation and impulsivity on sports performance, according to the gender and competition level in national-level volleyball players.post-hoc) was carried out for playing positions analysis. Spearman's correlation was performed between the performance and the variables of impulsivity and emotional regulation.In total, 77 players from the 2018–2019 top two Spanish divisions completed the ERQ (emotion regulation) and the UPPS-P (impulsivity). Statistics  were retrieved from the Spanish Volleyball Federation. A Mann–Whitney test was conducted to determine differences between gender and competition level in impulsivity and emotion regulation. A Kruskal–Wallis test (Mann–Whitney The results obtained, with differences according to playing position, gender, and competition level, show that players differ in certain psychological aspects that might influence how they approach their game.The results point in a promising direction: the sports practice analyzed can serve as a regulation context, for both the emotional response and the level of impulsivity of the players. The importance of these results for future research on this topic is discussed. To achieve successful results in sports, coaches commonly evaluate technical, tactical, or physical aspects. Playing volleyball entails constant short-term decision-making, by which, depending on the time available, athletes process the environmental information consciously or unconsciously Acker, . Thus, iIn sports, decisions are frequently unconscious and influenced by essential or incidental emotions Qiu, . Essentiby Gross and John , suppresimpulsivity as “a predisposition toward rapid, unplanned reactions to internal or external stimuli without regard to the negative consequences of these reactions to the impulsive individual or others” (p. 1784). Impulsivity affects performance in tasks when control is needed, and this interference can be increased in situations of decision-making  and some dimensions of impulsivity, precisely negative urgency, and lack of premeditation . How do these variables relate to the players' performance, playing position, gender, and level of competition? The authors hypothesized that they could be related to individual performance depending on the playing position, gender, and level of competition. In addition, it is suggested that players with a higher competitive level regulate their emotions better and have lower levels of impulsivity.In total, 77 volleyball players  from the top two Spanish divisions took part in the study. All of them were fluent in Spanish . The data were collected confidentially after the competitive season's ending under the Institutional Review Board guidelines of the University of Granada  and following the Declaration of Helsinki . InformeIn order to assess both ER strategies, Gross and John  developeA standard tool to measure impulsivity is the UPPS-P . Certified operators register the statistics by the Spanish Volleyball Federation, who are instructed to follow the same criteria to obtain reliable information, so it is assumable that the collected data fulfill the required reliability. Based on the performance, liberos and middle blockers cannot be compared, whereas setters and wing spikers share one common action (serve). With this in mind, only the differences between wing spikers and middle blockers can be explained by comparing their performance in two actions. Therefore, three performance variables for serve and attack combined were calculated: error ratio (Equation 1), efficacy (Equation 2), and efficiency (Equation 3).The player statistics  during the 2018/2019 season were collected from the Spanish Volleyball Federation , wing spikers (39), middle blockers (19), and liberos (14). This classification is an adaptation from the one used by Millán-Sánchez et al. .The staff of 16 volleyball teams of the top two Spanish divisions were contacted to participate in this study. In total, 10 of those teams responded positively and were visited on their usual training session schedule, after the competitive season, in an interval of 4 weeks. The players were informed about the study and instructed on how to complete the ERQ and the UPPS-P questionnaires, both in Spanish. The participants signed the informed consent forms and completed the questionnaires before their training session. The playing positions , gender , and category (first or second division) of the players were stated in the questionnaires.r, whose formula is z/√(n), where z is the z-statistic and n is the number of observations. Its interpretation follows the Cohen guidelines  were computed for the whole sample. There were no missing values. Outliers  were not removed in order not to decrease the sample size. Shapiro–Wilk normality tests showed that the ER and impulsivity variables did not present a normal distribution. Therefore, non-parametric analyses were conducted. A Mann–Whitney test was conducted to determine differences between gender and competition level in ER and impulsivity. The effect size was calculated with s Cohen, : 0.10 repost-hoc was conducted to determine the groups significantly different, with their respective effect size (r). Finally, Spearman's correlation (ρ) was performed between the variables of performance and the variables of ER and impulsivity in order to check their relationship. The level of significance was established at 0.05 for all the analyses. The statistical instrument used was SPSS for Windows, version 22.0  and JASP version 0.10 .Moreover, when significant results were observed, a U of Mann–Whitney The data concerning the playing position are presented in The descriptive data regarding gender and competition level are presented in p < 0.05) and with the SS . No significant correlations were found with the remaining dimensions of impulsivity  and the variables of ER . The correlation with the NU was small and with the SS was medium, according to Cohen . Given these results, only the differences between wing spikers and middle blockers can be explained by comparing their performance in two actions. Thus, we calculated the error ratio, efficacy, and efficiency for serve and attack altogether and correlated it to the different dimensions of impulsivity . A correto Cohen . The eff2 = 14.826; p = 0.002; R2E = 0.20) according to the playing position.A Kruskal–Wallis test was conducted for all the dependent variables . Resultspost-hoc U of Mann–Whitney was conducted to assess pairwise differences for NU , wing spikers and middle blockers , and middle blockers and liberos .A s for NU . SignifiZ = 2.480; p = 0.013; r = 0.283). Also, significant differences were found between competition levels in SS, showing second division players higher values . No other differences were found in neither impulsivity nor ER.The relationship between ER, impulsivity, and performance has been scarcely studied in a sports context. We hypothesized that these personality and emotional variables could be related to individual performance depending on the playing position, gender, and level of competition.Concerning performance, NU and SS correlated positively with the error ratio. Significant differences were found between playing positions in one dimension of impulsivity, namely NU, but not in the rest of the dimensions and ER. Likewise, female players presented higher NU than male players, and second division players showed higher SS than the top division players.On correlating performance with the variables of ER and impulsivity, the error ratio was statistically associated with the NU and the SS. The results suggest that those players with a higher NU and SS made more mistakes when performing their serves and attacks. These findings follow the same tendency as those obtained by Castillo-Rodríguez et al. , who alsConcerning ER, elite volleyball players do not show differences according to their playing positions, which means that players tend to use both ER strategies, reappraisal, and suppression, independently of their playing position. A possible explanation is that, as happens with university athletes  and 18.9  years old, compared to our 24.4 mean year-old sample. Age plays an essential role in impulsivity, as it decreases between adolescence and adulthood   Cohen, . Other s) Cohen, . Given tFurthermore, second division players presented a slightly younger mean age than first division players, although the age difference does not influence the result  to know their players' emotional traits and design training processes accordingly.Identifying the factors that affect athletes' performance is essential for developing effective interventions. In the case of volleyball, training in technical and physical skills is crucial for optimal player performance. However, it has also been demonstrated that players' ability to regulate their emotions and manage impulsivity is critical for success on the court. Therefore, coaches and therapists could work with volleyball players to develop effective emotion regulation and impulsivity reduction strategies. For example, visualization techniques could help players manage their anxiety before an important match. A mindfulness training program could also enhance players' ability to stay present-focused and reduce impulsivity in high-pressure situations. These interventions can improve players' performance and emotional wellbeing, which can positively impact the team as a whole.This study's sample is composed of professional and highly specialized players, with everything that means concerning the possibility to be accessed and studied. An increase in the sample size might cause a decrease in the value of the result, in terms of specificity and competitiveness (Lago Peñas et al., 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 Comité de Ética en Investigación de la Universidad de Granada. The patients/participants provided their written informed consent to participate in this study.AM-S, DC, RV, and AU contributed to the conception and design of the study. RV provided expert background. AM-S collected the data. IM and AM-S performed the data analysis. AM-S and AU wrote the first draft of the manuscript. All authors revised and edited the different versions of the manuscript and approved the submitted version.


Malignant mesothelioma (MM) is a rare aggressive tumor, and bone metastasis often occurs in later stages of this disease. This study aimed to establish a nomogram to predict the prognosis of bone metastasis of patients with MM. Data from the Surveillance, Epidemiology, and End Results database were screened and retrieved. This study included 311 patients with MM with bone metastases. Prognostic factors were analyzed using the Kaplan–Meier method and Cox proportional hazards model. A nomogram for overall survival (OS) was established and evaluated using statistically significant prognostic factors, and cancer-specific survival (CSS) analysis was performed to investigate its prognostic factors. In addition, the metastasis patterns of patients with MM were investigated, and the effects of different sites of metastasis on survival were compared using the Kaplan–Meier method. Age, sex, histological type, and chemotherapy were identified as the independent risk factors for OS. The 1-, 2-, and 3-year areas under the curve of the nomogram were 0.792, 0.774, and 0.928, and 0.742, 0.733, and 0.733 in the training and validation sets, respectively. Compared to OS, histological type, radiotherapy, and chemotherapy were independent risk factors for CSS. Different metastatic sites in MM have significantly different effects on prognosis. The tunica of the testis and ovary is rarely affected2. MM is highly correlated with asbestos exposure3. According to a systematic analysis of the 2019 Global Burden of Disease Study, across 204 countries and territories, the age-standardized incidence rate of MM reached 0.4  in 20194. Despite the decrease in the figure in the past decades due to restrictions on asbestos exposure, it continues to increase in many territories5. Bone metastasis often occurs in the later stages of MM, and distant metastasis of tumors is often associated with worse prognosis. Therefore, it is important to study the prognosis of bone metastases in patients with MM in the clinical decision-making process.Malignant mesothelioma (MM) is a rare aggressive tumor that mostly originates in the pleura (65–70%) and peritoneum (30%), and less commonly in the tunica vaginalis testis and pericardium (1–2%)1. However, most studies have focused on malignant pleural mesothelioma (MPM), a subtype of MM. Except for MPM, there is no definitive treatment method for other types of MM, so it is necessary to consider other types of MM for research6. Studies using nomograms for bone metastasis in patients with MM based on population-based data have not been reported. Therefore, we developed a nomogram using the Surveillance, Epidemiology, and End Results (SEER) database. Our findings may provide a batter understanding of patients with MM with bone metastases. In addition, no previous study has explored the metastatic patterns of MM in detail. In this study, the number of distant metastases of MM at each site was counted, and Kaplan–Meier analysis was used to evaluate the difference in the prognosis of MM according to different metastatic sites.Previous studies have suggested that MM has a wide range of prognostic factors. Sex, histological type, and treatment, affect the survival of patients7, (accession number: 12916-Nov2021), using SEER*Stat 8.4.0. Data were collected from patients with MM with bone metastases between 2000 and 2019.The SEER database is a publicly available U.S. government-funded database that focuses on clinical information on patients with cancerThe primary cohort was selected as follows: (1) all cases identified as MM with ICD-O-3 histological type codes 9050/3, 9051/3, 9052/3, 9053/3, and 9055/3 and (2) all MM cases with bone metastases.The exclusion criteria for the primary cohort were as follows: (1) cases without microscopic confirmation of an MM diagnosis and (2) cases with unknown clinical variables included in this study.In addition, to investigate the effects of metastatic sites other than bone metastases on overall survival (OS), a data set including other metastatic sites was also included. The secondary cohort was selected as follows: all cases identified as MM with ICD-O-3 histological type codes 9050/3, 9051/3, 9052/3, 9053/3, and 9055/3.The exclusion criteria for the secondary cohort were as follows: (1) cases without microscopic confirmation of an MM diagnosis and (2) cases with unknown metastatic sites.Clinical variables included demographic , tumor-related , therapy-related , and survival-related  information. There were 13 variables in the final survival analysis.In the SEER database, distant metastasis sites include the bone, brain, liver, and lung. Distant metastases were classified into 15 groups according to the different metastatic sites: four groups of single-organ, six groups of two-organ, four groups of three-organ, and one group of four-organ metastases.Using R version 4.1.2  to preprocess the data with 344 samples, some cases were removed based on the exclusion criteria. The case selection flowchart is shown in Supplementary Figure OS is defined as the time from diagnosis to death. For OS, univariate Cox regression analysis was performed on the 13 extracted variables. Then statistically significant predictors from the univariate analysis were included in the multivariate Cox regression, and variables with two-tailed p < 0.05 were considered statistically significant. The hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. For independent risk factors affecting survival, survival curves were drawn using the Kaplan–Meier method to determine the relationship between independent risk factors and survival, and the log-rank test method was applied for comparative analysis. The same analysis was performed for cancer-specific survival (CSS), which was measured as the time from diagnosis to death due to MM.After data preprocessing, 311 cases were divided into a 70% training set and a 30% validation set. The 1-, 2‐, and 3‐year OS probabilities were estimated using a nomogram based on the results of the independent risk factors. The model was evaluated using the receiver operating characteristic (ROC) curve. All statistical analyses were performed using R version 4.1.2 .The data used in this study are publicly available and do not require approval from the ethics committee. All methods were carried out in accordance with relevant guidelines and regulations.Data from 344 patients diagnosed with MM with bone metastases were collected from the SEER database. After excluding patients whose clinical variables were unknown, 311 patients were included in the data analysis. Table Variables found to be significantly associated with OS were sex, age, race, marital status, income, histological type, radiotherapy, and chemotherapy. After incorporating these variables into the multivariate analysis, the results showed that sex, age, histological type, and chemotherapy were independent risk factors for OS Fig. . CombineVariables found to be significantly associated with CSS were race, age, histological type, radiotherapy, and chemotherapy were significantly associated with CSS. These variables were included in the multivariate analysis. The results showed that histological type, radiotherapy and chemotherapy were independent risk factors for CSS Fig. . CombineBased on the training set for the OS analysis, we constructed an OS nomogram based on four independent risk factors affecting OS Fig. . AccordiThe nomogram, as a commonly used clinical prediction model, can have varying effects depending on the specific population and application scenario. Therefore, to verify that the nomogram can accurately predict outcomes in a clinical setting, it is necessary to test it on another population that was not included in the training set. Using the validation set as the internal validation data set, the discriminative degree of the model was evaluated by the area under the curve (AUC) and decision curve analysis assess the clinical utility of the model.When we use it, we often estimate the probability of an event by making a perpendicular line. In this study, gender, age, histological type of MM, and whether chemotherapy has been performed can be calculated based on the column chart. Then, the total score of the individual can be obtained by adding the above scores, and the probability of occurrence corresponding to the total score can be estimated based on the column chart, which is the probability of death of the individual.In the upper left corner of the ROC, sensitivity = 1, and specificity = 1. Accordingly, the closer the ROC curve is to the upper left corner of the graph, the higher the accuracy of the test. Therefore, the AUC of the ideal ROC curve is 1. As shown in Fig. In the MM cohort with distant metastases, 840 patients had distant metastases. The most common was single lung metastasis (325 cases), accounting for 38.69% of patients with MM with distant metastasis. Single bone (22.98%) and liver (16.55%) metastases were also more common. Single brain metastases were rarer than other single-site metastases, with only 15 (1.79%) cases. Most patients had single-organ metastasis, accounting for 80% of the cases. The most common metastases in two organs were bone and lung metastases, with 57 cases, accounting for 6.79% of the cases. Among the three-organ metastases, the most common were bone, liver, and lung metastases, accounting for 21 (2.5%) cases. The detailed results are shown in Supplementary Table Among patients with MM with metastases, single bone, lung, and liver metastases were the main types, accounting for 78% of the total metastatic population. The log-rank test and Kaplan–Meier analysis showed that there were differences in the survival rates of these three groups, with the best prognosis for liver metastasis and the worst prognosis for bone metastasis  were independent risk factors, and a nomogram was constructed for useful clinical application. Survival analysis showed that age, sex, histological type, and chemotherapy were independent risk factors for OS in patients with MM with bone metastases. Radiotherapy, chemotherapy and histological type were independent risk factors for CSS. However, it is important to note that histology and chemotherapy are not entirely independent risk factors as the histology influences the decisions about chemotherapy11. Earlier studies have shown that the majority of cases occur in men12, which is also reflected in our data; this may be related to occupational exposure to asbestos. Studies also have suggested that male patients had a worse prognosis compared to female patients with MM13. MM can occur at any age, and increasing age is an independent risk factor for MM14. Epithelioid malignant mesothelioma is characterized by diffuse and invasive growth of epithelioid cells from pleural surface, biphasic malignant mesothelioma is characterized by having both epithelioid and sarcomatoid components, sarcomatoid malignant mesothelioma is characterized by diffuse and infiltrative growth of spindle cells or mesenchymal cells15. Epithelial type tumors are the most common subtype of MM, and the non-epithelioid subtype is indicated in the guidelines for the pathological diagnosis of MM as a pathological factor associated with poor prognosis11, which has been confirmed in single-institution clinical studies16. Our study results were consistent with those of previous studies identifying prognostic risk factors.Recently, many studies have performed survival or epidemiological analyses of MM; however, the vast majority have focused on MPM. Some studies have used the SEER database to analyze MM17. Pemetrexed and cisplatin combination chemotherapy are common treatment options, but the benefits of the regimen are limited, prognosis remains poor18. Moreover, radiotherapy helps in controlling tumor invasion19. In our study, chemotherapy was an effective treatment method for prolonging OS in patients with MM with bone metastasis. Moreover, radiotherapy and chemotherapy were significantly associated with CSS.An increasing number of studies have focused on the treatment of MM, with options including surgery, radiotherapy, chemotherapy, and immunotherapy. Whether surgery can be performed is guided by the different age, performance status, and histological type of patientsFew studies have emphasized the role of distant metastasis in the prognostic assessment of MM, and the SEER database contains information on four types of metastatic sites. In our study, the rate of distant metastasis in MM was 12%, the top three patterns among the 15 types of metastases were single lung, single bone, and single liver metastases. Once a tumor metastasizes to the bone, it is usually incurable. The destructive consequences of bone metastasis include pathological fractures, pain, hypercalcemia, and spinal cord and nerve compression syndrome. Skeleton can also serve as a reservoir for dormant cancer cells in other organs, and bone metastasis of tumors may lead to comprehensive metastasis after prolonged dormancy. The Kaplan–Meier analysis showed that patients with liver metastasis had a batter prognosis, and that patients with bone metastasis had a worse prognosis, However, more data is needed in the future to support this conclusion. The information provided by the SEER database covers a comprehensive population, and its authenticity can be guaranteed.However, this study has some limitations. First, this study did not conduct external validation because there was no external validation dataset. Second, the integrity of the data was difficult to guarantee owing to the many missing values. Third, in the SEER database, the treatment values of “no” and “unknown” are indistinguishable, which inevitably have effects on the analysis results.20 and oral cavity21. Further studies with different demographics and larger sample sizes should be conducted in the future.In addition, there are only four metastatic sites in the SEER database; however, MM can also metastasize to other sites, such as the skinAge, sex, histological type, and chemotherapy are independent risk factors for OS. The OS nomogram constructed based on the above four prognostic factors has satisfactory accuracy, and its clinical utility may benefit clinical decision-making. Single-organ metastases in patients with MM are the most common, and different metastatic sites have significantly different effects on prognosis.Supplementary Information 1.Supplementary Information 2.


Background: Multiple sclerosis (MS) is a disease of the central nervous system characterized by inflammation, demyelination, and axonal degeneration. This study aimed to investigate the relationship between inflammatory indexes and MS disease activity and progression. Methods: A prospective cohort study was conducted at the Kocaeli University Neurology Clinic, involving 108 patients diagnosed with MS. Data related to patient demographics, clinical presentations, radiological findings, and laboratory results were recorded. Inflammatory markers such as NLR (neutrophil-to-lymphocyte ratio), PLR (platelet-to-lymphocyte ratio), MLR (monocyte-to-lymphocyte ratio), and indexes such as SII (systemic immune inflammation index), SIRI (systemic immune response index), and AISI  were examined to determine their correlation with MS disease activity and disability. When assessing the influence of SII, AISI, and SIRI in predicting NEDA, it was found that all three indexes significantly predict NEDA. All indexes demonstrated a significant relationship with the EDSS score. Notably, SII, SIRI, and AISI were significant predictors of NEDA, and all inflammatory indexes showed a strong intercorrelation. This study investigates the role of inflammation markers in MS patients. It suggests that one or more of these non-invasive, straightforward, and practical markers could complement clinical and radiological parameters in monitoring MS. Multiple sclerosis (MS) is a complex neurological disease that affects an estimated 2.5 million people worldwide and has significant socio-economic consequences. Inflammation plays an important role in disease progression and symptom onset in MS, a central nervous system (CNS) disease characterized by demyelination and axonal disruption. The origins of the disease are multifaceted, and its pathogenesis relies on a combination of genetic, environmental, and immunologic factors. The complex nature of its causes makes MS a challenging condition to understand and manage, emphasizing the need for extensive research and targeted therapeutic interventions . This complexity not only complicates our full understanding of the disease’s pathogenesis but also poses one of the greatest challenges to achieving successful treatment outcomes. The primary cause of the inflammatory processes observed in multiple sclerosis is believed to be the peripheral activation of Th1 cells that interact with myelin autoantigens and then migrate to the central nervous system. Upon activation, these T-cells attract various myeloid cells, including monocytes and macrophages, triggering an inflammatory response that often results in axonal transection and irreversible localized CNS damage .Therapeutic targets in the MS field are continuously evolving due to recent advances in disease-modifying treatments (DMTs) . It is wA complete blood count (CBC) test measures the number and morphology of various cell types in the blood. White blood cells, neutrophils, lymphocytes, erythrocyte sedimentation rate, and C-reactive protein (CRP) are commonly used markers for evaluating inflammation. While these characteristics can indicate the presence and degree of inflammation, they alone are not sufficient for a definitive diagnosis. Ratios derived from hemogram parameters, such as neutrophil-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR), have been used as inflammation indicators in numerous diseases ,8,9,10. The systemic immune-inflammatory index (SII), which comprises neutrophil, lymphocyte, and platelet counts, has recently been recognized as a new measure of inflammation. SII can serve as a biomarker in various conditions and may indicate systemic inflammation. According to research, SII has been associated with MS disease activation, MRI activation, and disability ,12. OtheThe idea of identifying easy and practical biomarkers and adding other markers to patient follow-up and monitoring has attracted much attention in the last decade. However, biomarkers that are potentially more noninvasive for patients and that can be obtained from routine examinations may be more promising than expected. The aim of this study was to explore the relationship between easily accessible, cost-effective, and non-invasive serum inflammatory biomarkers and MS disease activity and disability. Additionally, the predictive value of the inflammatory parameters  for NEDA was examined.This prospective cohort study was conducted from April 2021 to May 2023. Patients who achieved NEDA-3 by the end of the second year following the initial evaluation were included in the study. Over the course of two years, patients underwent examinations every six months by one blinded neurologist MS specialist. An MRI was performed annually, ensuring that each patient had a minimum of three MRI evaluations at baseline, after the first year, and after the second year. MRI findings were assessed by two blinded neurologists. The ethics committee of the Kocaeli University Faculty of Medicine approved the study (GOKAEK-22/06.11). Informed consent was obtained from each patient for the study.A total of 108 MS patients followed in the Kocaeli University Neurology Clinic were included in the study. Inclusion criteria were that patients must have been diagnosed with relapsing-remitting MS, have been on the same medication for at least a year, be 18 years or older, and meet the 2017 revised McDonald criteria. Patients were excluded for neurological or psychiatric illnesses, chronic conditions such as thyroid disorders, coronary artery disease, diabetes mellitus, malignancy, a recent history of infection, or if they had an attack or received corticosteroid treatment in the last three months. All participants included in the study were selected from patients who had used a DMT (a group whose treatment had not changed in the last year) for at least one year. The patients’ demographic data, such as age, gender, and body mass index (BMI), and their clinical, radiological, and laboratory evaluations were recorded in a case report form. EDSS scores were calculated following their neurological examinations. All participants underwent the timed 25-foot walk test (T25FWT), the 9-hole peg test (NHPT), and the symbol digit modalities test (SDMT). The T25FW test was used to assess lower extremity function. In this test, the time taken by the patient to cover a distance of 25 feet (approximately 8 m) is measured. The test is repeated twice and averaged. Upper extremity function was assessed using the NHPT. This test involves inserting pegs into nine holes as quickly as possible. The test is repeated four times, twice for each hand, and an average result is obtained. SDMT is a short, easy to administer, and understandable test used to assess cognitive status and especially information processing capacity in neurological diseases. In the SDMT, the patient is asked to write the digit specified in the proposition under each figure as fast as possible in 90 s by looking at the proposition in which certain geometric shapes are paired with certain numbers. Responses can be written or verbal. At the end of 90 s, the number of correct and incorrect answers is recorded. Additionally, the DMTs taken by the patients were recorded. For disease activity assessment, the study group was categorized according to NEDA-3 status at the end of the second year. NEDA’s sub-parameters were defined as relapse, MRI activity , and EDSS progression. At the end of the second year, blood samples were collected within two weeks from patients who achieved NEDA-3. Patients who had a history of infection in the last two weeks, those who had used anti-inflammatory drugs, antibiotics, or antiviral medications in the previous two weeks, patients currently menstruating, and patients who had taken corticosteroids in the last three months were excluded.All MRI examinations were performed using the same MRI device . In the MRI examination, T1-weighted sequences, T1-weighted sequences with gadolinium, T2-weighted sequences, and fluid-attenuated inversion recovery (FLAIR) sequences were utilized. All venous blood samples were collected using potassium ethylenediaminetetraacetic acid (EDTA) tubes (Beckman Coulter UniCel D × H 800). The CBC was assessed within one hour of collection using a blood cell analyzer. The Sysmex XN-1000 series blood cell analyzer has adopted three key technologies for blood cell analysis: semiconductor laser flow cytometry, which detects structural changes in cells; direct current sheath flow measurement method used to count red blood cells and platelets; sodium lauryl sulfate (SLS)-hemoglobin method, which measures hemoglobin concentration.In addition, surfactants and markers were used to differentiate cells based on their marking intensity and membrane resistance. The reagents required for these processes were provided by companies such as Becton Dickinson and Company of Japan, Stemcell Technologies, and Hitachi High-Technologies. The samples were tested for lymphocyte, monocyte, platelet, and neutrophil levels. All serum samples were collected between 08:00 and 09:00. The calculation formulas for all inflammation indexes included in the study are provided in p-value of less than 0.05 was considered statistically significant. The normality of the data distribution was assessed using the Shapiro–Wilk test, and by examining histograms and plots. For data with a normal distribution, the mean and standard deviation values are provided. For data without a normal distribution, the median value (min–max) is provided. Frequencies in categorical data are presented as percentages. The nonparametric Mann–Whitney U test was used to compare the means of two independent groups with non-normally distributed data, while the student t-test was used for normally distributed data. To compare the means between more than two groups, the nonparametric Kruskal–Wallis analysis of variance was used. The Spearman correlation test determined the direction and strength of the relationships between variables. The effects of SII, AISI, and SIRI in predicting NEDA in the study group were analyzed using binary logistic analysis.The Windows Statistical Package for Social Sciences (SPSS) version 22.0 was used for all statistical analyses to evaluate the study data. A A total of 108 MS patients were included in the study, of which 71 (65.7%) were women. The average age was 37.45 ± 9.36 years. The median disease duration in the study group was 65 months (13–288); median EDSS score 1.5 (0.5–5); median BMI value 25 (15.70–33.20); mean SDMT score 34.80 ± 12.48; median NHPT (D) time 22.07 s (15.04–60.97); median NHPT (L) time 23.67 s (14.71–60.51); and median T25FWT time 11.79 s (2.50–35.00).Hemogram values, biochemical data, and the indexes derived from this data for the study group are presented in p < 0.001). There was no difference in terms of age and gender between the group that achieved NEDA-3 and the group that did not. Inflammation indexes were higher in the group that achieved neda-3 than in the group that did not achieve neda-3. Significant findings based on the presence of NEDA are provided in When evaluating the study group based on NEDA status, 50% of the patients (54/108) achieved NEDA. The EDSS scores of the NEDA-achieving group were significantly lower than those who did not  of the group. On the other hand, 10 patients (18.5%) had a new T2 lesion, and 9 (16.6%) had a Gd+ lesion. As a result, while MRI activation was observed in 19 patients (35.1%), relapse was observed in only 4 (7%) of the group that did not achieve NEDA .p = 0.023 and p = 0.008, respectively). A slight negative correlation was also observed between age and SDMT . Correlations between physical parameters and inflammation markers are presented in Upon examining the relationship between the study group’s demographic characteristics and their physical and cognitive parameters, a mild correlation was found between age and both NHPT (D) and NHPT (L) times . In the study group, the effectiveness of SII, AISI, and SIRI in predicting NEDA was assessed with binary logistic analysis. All three indexes were found to significantly predict NEDA. Age, BMI, and gender showed no significant effect. An increase of one unit in AISI and SII values raised the likelihood of achieving NEDA by 1.001 times, while a one-unit increase in SIRI increased this likelihood by 1.51 times   .p < 0.001). However, the DMD groups were compared using the Kruskal-Wallis test in terms of SII, SIRI, and AISI values; no significant relationship was detected between the three indexes and lymphocyte values (p > 0.05)  .There have been many studies on the potential of inflammatory biomarkers to predict disease activity or prognoses in the monitoring of MS. This study investigated the overall efficacy of inflammatory biomarkers for disease activity, physical disability, and cognitive impairment. In our research, the inflammatory indexes were found to be higher in the NEDA-3 group. While there was a significant relationship between EDSS, T25FWT, and inflammatory indexes, no association was observed between NHPT and SDMT. The correlations among the inflammatory indexes displayed very strong positive relationships with one another. Moreover, we assessed the predictive value of the inflammatory indexes for NEDA-3 status (for 2-year NEDA) and found that all three parameters  were strong predictors of NEDA-3.In general, the functions of the upper extremities and limbs can be influenced by age. Older MS patients may take slightly longer to complete NHPT and T25FWT compared to younger individuals ,16. ConsIn MS, the inflammation and neurodegenerative processes are complex. Recently, serological inflammatory indexes, combined with clinical, laboratory, and radiographic indicators, have been studied. Comprehensive investigations, including serum biomarkers, can offer insights into subclinical inflammation ,20. WhilThe neutrophil-to-lymphocyte ratio (NLR) is a simple, rapid, nonspecific, and cost-effective method for identifying systemic inflammation. Compared to healthy controls, individuals with autoimmune diseases, such as Sjogren’s syndrome, sarcoidosis, ulcerative colitis, rheumatoid arthritis, and MS, have shown higher NLR values . NumerouPLR is another immunological inflammatory marker. Unlike NLR, PLR accounts not only for leukocyte subsets but also for platelet numbers . One stuWhile NLR and PLR are determined by the ratios of two distinct blood cell populations, the SII index combines all three populations by multiplying NLR with platelet counts . One stuIn recent years, biomarkers such as kappa immunoglobulin free light chain concentration, kappa cerebrospinal fluid (CSF) index proposed as an alternative to oligoclonal bands, neurofilament light chain, glial fibrillary acidic protein, and myelin basic protein have been extensively studied in CSF and serum to assess disease activation and progression in MS . HoweverIn recent years, there has been extensive discussion about the use of NEDA—the absence of evidence of disease activity—in follow-up as a measure to evaluate therapy response. In this study, when comparing groups that achieved NEDA-3 to those that did not, all inflammatory parameters were found to be significantly higher in the group that achieved NEDA-3 for two years. This raises questions about the true definition of NEDA. There may be several reasons why many neurologists are cautious about using NEDA in clinical practice. While NEDA is a comprehensive indicator, its sub-parameters, including clinical relapses, disability progression, and MRI activity, can be difficult to interpret reliably. There are concerns that reliance on NEDA alone may miss subtle but important changes in a patient’s health. Moreover, strict NEDA criteria may not capture the full spectrum of disease variations, potentially leaving gaps in treatment approaches ,30,31,32In the current study, when the indexes and lymphocyte values were examined based on the DMTs used by the patients, no significant relationship was established between the indexes and lymphocyte counts. This may refute the view that drugs that cause lymphopenia can affect the inflammation index.One limitation of this study is that although factors potentially affecting systemic inflammation within the study group were controlled, it must be acknowledged that these indexes could be influenced by factors such as disease-modifying drugs and individual characteristics. Another limitation of the study is that a healthy control group was not included as a third group. The presence of a healthy control group would have allowed us to evaluate the results from a broader perspective. However, the main aim of this study was to determine how disease activity in MS can be associated with markers of inflammation on the basis of NEDA. In this context, patients meeting and not meeting NEDA criteria were used as control groups against each other. Ratios derived from hemogram parameters such as NLR, PLR, and MLR are often used as an indicator of systemic inflammation. One of the limitations of this study is that these markers are non-specific in nature and may vary in many different pathologic conditions. However, in order to reduce this limitation while designing our study, conditions that may affect systemic inflammation parameters were determined as exclusion criteria. We would also like to point out that both groups in our study were selected homogeneously. The limitations of this study include the fact that these biomarkers were not analyzed in CSF. However, this does not invalidate the results of the study; it should only be taken into account in the interpretation of the results.Our study is a preliminary study examining inflammatory parameters in MS based on NEDA. A key strength of this research is its focus on inflammation indexes alongside achieving 2-year NEDA-3 status. We investigated the association between the absence of disease activity and the systemic inflammatory response. Our findings suggest that systemic inflammation parameters could serve as potential biomarkers to uncover ongoing subclinical activity in the group achieving NEDA-3. This finding highlights the potential importance of considering systemic inflammation parameters. It may be useful to monitor inflammation-related biomarkers even in the absence of clear clinical signs of disease activity. Despite all its limitations, considering that the concept of NEDA will be questioned in depth in light of the data obtained from this study, it is thought that our study may contribute to future research in this direction. In the future, we aim to conduct a more comprehensive study on larger patient cohorts with a control group of healthy donors, addressing different clinical models of multiple sclerosis, different disease activities and other biomarkers. If these efforts lead to the discovery of inflammatory parameters with sufficiently high specificity, further studies will be needed to evaluate them not only in multiple sclerosis but also in other immune-related and neurodegenerative diseases such as Parkinson’s disease. Only then will it be possible to determine how specific and therefore useful these new markers could be in clinical practice.Biomarker studies for both diagnostic and prognostic purposes in multiple sclerosis are crucial. As the medical community seeks more precise tools for diagnosis and prognosis, the value of biomarkers is becoming increasingly apparent. Recently, hemogram-derived data, which serve as a biomarker, have been increasingly utilized in various diseases. In conditions like MS, where it is challenging to assess the degree of inflammation and neurodegeneration, the significance of gleaning prognostic insights from easily accessible data in routine clinical practice is evident. This research delved into systemic inflammatory markers, such as NLR, PLR, MLR, SII, SIRI, and AISI, in MS patients. The choice of these markers stems from their potential to provide a window into the underlying inflammatory processes in MS. All of these indexes demonstrated notable correlations with physical metrics and exhibited robust interrelationships. A pivotal finding of this study is the novel revelation that SII, SIRI, and AISI can be indicators for NEDA-3 in MS. It is postulated that incorporating one or more of these non-invasive, straightforward, and practical markers with clinical and radiological criteria can enhance the monitoring of MS progression.