Immunologic tumor microenvironment modulators for turning cold tumors hot.

Tumors can be classified into distinct immunophenotypes based on the presence and arrangement of cytotoxic immune cells within the tumor microenvironment (TME). Hot tumors, characterized by heightened immune activity and responsiveness to immune checkpoint inhibitors (ICIs), stand in stark contrast to cold tumors, which lack immune infiltration and remain resistant to therapy. To overcome immune evasion mechanisms employed by tumor cells, novel immunologic modulators have emerged, particularly ICIs targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1/programmed death-ligand 1(PD-1/PD-L1). These agents disrupt inhibitory signals and reactivate the immune system, transforming cold tumors into hot ones and promoting effective antitumor responses. However, challenges persist, including primary resistance to immunotherapy, autoimmune side effects, and tumor response heterogeneity. Addressing these challenges requires innovative strategies, deeper mechanistic insights, and a combination of immune interventions to enhance the effectiveness of immunotherapies. In the landscape of cancer medicine, where immune cold tumors represent a formidable hurdle, understanding the TME and harnessing its potential to reprogram the immune response is paramount. This review sheds light on current advancements and future directions in the quest for more effective and safer cancer treatment strategies, offering hope for patients with immune-resistant tumors.

Insights into the interplay between Epstein-Barr virus (EBV) and multiple sclerosis (MS): A state-of-the-art review and implications for vaccine development.

Background and Aims: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS). MS results from an inflammatory process leading to the loss of neural tissue and increased disability over time. The role of Epstein Barr Virus (EBV), as one of the most common global viruses, in MS development has been the subject of several studies. However, many related questions are still unanswered. This study aimed to review the connection between MS and EBV and provide a quick outline of MS prevention using EBV vaccination. Methods: For this narrative review, an extensive literature search using specific terms was conducted across online databases, including PubMed/Medline, Scopus, Web of Science, and Google Scholar, to identify pertinent studies. Results: Several studies proved that almost 100% of people with MS showed a history of EBV infection, and there was an association between high titers of EBV antibodies and an increased risk of MS development. Various hypotheses are proposed for how EBV may contribute to MS directly and indirectly: (1) Molecular Mimicry, (2) Mistaken Self, (3) Bystander Damage, and (4) Autoreactive B cells infected with EBV. Conclusion: Given the infectious nature of EBV and its ability to elude the immune system, EBV emerges as a strong candidate for being the underlying cause of MS. The development of an EBV vaccine holds promise for preventing MS; however, overcoming the challenge of creating a safe and efficacious vaccine presents a significant obstacle.

Global, regional, and national quality of care index of cervical and ovarian cancer: a systematic analysis for the global burden of disease study 1990-2019.

BACKGROUND AND OBJECTIVE: Cervical cancer is the most preventable and ovarian cancer is the most lethal gynecological cancer. However, in the world, there are disparities in health care performances resulting in differences in the burden of these cancers. The objective of this study was to compare the health-system quality of care and inequities for these cancers using the Quality of Care Index (QCI). MATERIAL AND METHODS: The 1990-2019 data of the Global Burden of Disease (GBD) was analyzed to extract rates of incidence, prevalence, mortality, Disability-Adjusted Life Years (DALYs), Years of Life Lost (YLL), and Years of healthy life lost due to disability (YLD) of cervical and ovarian cancer. Four indices were developed as a proxy for the quality of care using the above-mentioned rates. Thereafter, a Principal Components Analysis (PCA) was applied to construct the Quality of Care Index (QCI) as a summary measure of the developed indices. RESULTS: The incidence of cervical cancer decreased from 1990 to 2019, whereas the incidence of ovarian cancer increased between these years. However, the mortality rate of both cancers decreased in this interval. The global age-standardized QCI for cervical cancer and ovarian cancer were 43.1 and 48.5 in 1990 and increased to 58.5 and 58.4 in 2019, respectively. QCI for cervical cancer and ovarian cancer generally decreased with aging, and different age groups had inequitable QCIs. Higher-income countries generally had higher QCIs for both cancers, but exceptions were also observed. CONCLUSIONS: Uncovering disparities in cervical and ovarian cancer care across locations, Socio-Demographic Index levels, and age groups necessitate urgent improvements in healthcare systems for equitable care. These findings underscore the need for targeted interventions and prompt future research to explore root causes and effective strategies for narrowing these gaps.

Promising applications of nanotechnology in inhibiting chemo-resistance in solid tumors by targeting epithelial-mesenchymal transition (EMT).

The resistance of cancer cells to chemotherapy, also known as chemo-resistance, poses a significant obstacle to cancer treatment and can ultimately result in patient mortality. Epithelial-mesenchymal transition (EMT) is one of the many factors and processes responsible for chemo-resistance. Studies have shown that targeting EMT can help overcome chemo-resistance, and nanotechnology and nanomedicine have emerged as promising approaches to achieve this goal. This article discusses the potential of nanotechnology in inhibiting EMT and proposes a viable strategy to combat chemo-resistance in various solid tumors, including breast cancer, lung cancer, pancreatic cancer, glioblastoma, ovarian cancer, gastric cancer, and hepatocellular carcinoma. While nanotechnology has shown promising results in targeting EMT, further research is necessary to explore its full potential in overcoming chemo-resistance and discovering more effective methods in the future.

The prevalence of multiple sclerosis (MS) in Oceania, a systematic review, and meta-analysis.

BACKGROUND: Oceania is a continent, covering more than 8 million km2, with a population of more than 44 million people. In different countries landing in Oceania, various prevalence of MS has been reported, so we designed this systematic review and meta-analysis to estimate the pooled prevalence of MS in Oceania. METHODS: We systematically searched PubMed, Scopus, EMBASE, Web of Science, and Google Scholar. We also searched references of included studies, and conference abstracts. The search was done on January 1, 2023, by two independent researchers. We extracted the name of the first author, country, publication year, prevalence period, number of study participants, total female and male population, disease duration, type of MS, mean duration of the disease, mean age at disease onset, mean Expanded Disability Status Scale (EDSS), and total female and male patients with MS. RESULTS: A literature search revealed 81,044 records; after deleting duplicates, 38,260 records remained. One hundred and six full texts were evaluated, and finally, seventeen studies remained for systematic review. Most studies were done in Newcastle; eight studies were done in 1961, 8 in 1981, 2 in 1996, and 2 in 2001. In all other years, only one study was done. The pooled prevalence of MS in 1961 in Oceania was estimated as 19.85/100,000 (I2=70.3%, p=0.001). The pooled prevalence of MS in 1981 in Oceania was estimated as 39.07/100,000 (I2 =88%, p=0.001). CONCLUSIONS: The result of this systematic review and meta-analysis shows that the prevalence of MS has increased dramatically during the timespan in Oceania.

The relationship between retinal layer thickness and cognition in patients with multiple sclerosis: A systematic review of current literature.

Background: This study was conducted to evaluate the relationship between retinal layer thickness (RLT) and cognition in patients with multiple sclerosis (MS). Methods: We searched PubMed, Scopus, Embase, Web of Science, and Google Scholar. The search strategy included the MeSH and text words as ["ora serrata" OR "retina" OR ("coherence tomography" AND "optical") OR "OCT tomography" OR (tomography AND OCT) OR "optical coherence tomography" OR "OCT" OR "retinal thickness" OR "inner plexiform layer" OR "nerve fiber layer" OR "ganglion cell layer" OR "inner nuclear layer" OR "outer plexiform layer" OR "outer nuclear layer" OR "external limiting membrane" OR "inner segment layer" OR "outer segment layer" OR "retinal pigment epithelium"] AND ["cognition"* OR "cognitive function"* OR (function* AND cognitive)] AND [(sclerosis AND multiple) OR (sclerosis AND disseminated) OR "disseminated sclerosis" OR "multiple sclerosis" OR "acute fulminating"]. Results: The literature search revealed 1090 articles; after deleting duplicates, 980 remained. Finally, 14 studies were included. Totally, 1081 patients were evaluated. Mean age ranged from 31 to 55 years. In some studies, there was a correlation between cognition and retinal thickness, while others did not confirm this finding. Some authors found cognitive impairment (CI) in patients with MS with RLT. Conclusion: The results of this systematic review show that there are discrepancies between the results of studies regarding the relationship between RLT and cognition status in patients with MS. Further studies with more included original studies and meta-analysis are recommended.

Global and regional quality of care index (QCI) by gender and age in oesophageal cancer: A systematic analysis of the Global Burden of Disease Study 1990-2019.

BACKGROUND: The aim of this study was to examine the quality of care by age and gender in oesophageal cancer using Global Burden of Disease (GBD) database. METHODS: Patients aged 20 and over with oesophageal cancer were included in this longitudinal study using GBD 1990-2019 data. We used the Socio-Demographic Index (SDI) to classify the regions. We used Principal Component Analysis (PCA) method to calculate the Quality of Care Index (QCI). The QCI was rescaled into a 0-100 single index, demonstrating that the higher the score, the better the QC. RESULTS: The age-standardized QCI for oesophageal cancer dramatically increased from 23.5 in 1990 to 41.1 in 2019 for both sexes, globally. The high SDI regions showed higher QCI than the rest of the regions (45.1 in 1990 and 65.7 in 2019) whereas the low SDI regions had the lowest QCI, which showed a 4.5% decrease through the years (from 13.3 in 1990 to 12.7 in 2019). Globally, in 2019, the QCI showed the highest scores for patients aged 80-84, reported 48.2, and the lowest score for patients aged 25-29 reported 31.5, for both sexes. Globally, in 2019, age-standardized Gender Disparity Ratio (GDR) was 1.2, showing higher QCI in females than males. CONCLUSION: There were fundamental differences in the QCI both globally and regionally between different age groups as well as between males and females. To achieve the goal of providing high-quality services equally to people in need in all over the world, health systems need to invest in effective diagnostic services, treatments, facilities, and equipment and to plan for screening and surveillance of high-risk individuals.

The burden of rheumatoid arthritis and low back pain in North Africa and Middle East from 1990 to 2019: Results from the Global Burden of Disease Study 2019.

BACKGROUND: Rheumatoid arthritis (RA) and low back pain (LBP) are among the most prevalent musculoskeletal disorders (MSDs). The need for investigation of regional and local patterns of these two MSDs seems inevitable for better policy-making. The current study presents updated results of the Global Burden of Disease (GBD) Study 2019 and reports the burden of RA and LBP in North Africa and Middle East (NAME) countries from 1990 to 2019. METHODS: Incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life-years (DALYs), and risk factors, including high body mass index, occupational ergonomic factors, and smoking, were extracted based on the GBD 2019 data. RESULTS: The age-standardized prevalence and mortality of RA were 120.6 (95% uncertainty interval [95% UI] 107.0-135.7) and 0.1 (95% UI 0.1-0.2) per 100 000 population in 2019 with 28.3% (95% UI 25.5%-30.9%) increase and 7.5% (95% UI -37.5% to 32.5%) decrease since 1990, respectively. Turkey had the highest age-standardized incidence, prevalence, and DALYs of RA in 2019. All RA burden measures were higher for women; however, the incidence was almost the same at ages greater than 65 years. The age-standardized prevalence and DALYs of LBP were 7668.2 (95% UI 6798.0-8636.3) and 862 (95% UI 605.5-1153.3) in 2019, which had decreased by 5.8% (95% UI -7.4% to -4.3%) and 6.0% (95% UI -7.7% to -4.2%) since 1990, respectively. Moreover, although Turkey had the highest incidence and prevalence in 1990, Iran was at the top in 2019. The regional age-standardized DALY rates due to RA and LBP attributed to smoking were 1.7 (95% UI 0.5-3.2) and 139.4 (95% UI 87.3-198.8) in 2019, respectively, which had decreased 2.2% (95% UI -19.2% to 13.7%) and 15.4% (95% UI -19.4% to -10.5%) since 1990, respectively. CONCLUSION: RA still imposes a significant burden in the NAME region as the burden measures have increased from 1990 to 2019. On the other hand, regarding LBP, a decreasing pattern was observed. Differences among the countries and between ages and genders can have implications, and the results of this study may be helpful for policy-makers in the NAME countries.

Prevalence and risk of developing sexual dysfunction in women with multiple sclerosis (MS): a systematic review and meta-analysis.

OBJECTIVE: To estimate the pooled prevalence of sexual dysfunction (SD) in women with multiple sclerosis (MS). METHODS: We systematically searched PubMed, Scopus, EMBASE, Web of Science, and google scholar and also gray literature up to October 2021. The search strategy includes: ("Multiple Sclerosis" OR "MS" OR "Disseminated Sclerosis" OR (Disseminated AND Sclerosis) OR (Sclerosis AND Multiple)) AND ("Sexual Dysfunction" OR (Sexual AND Dysfunction) OR (Sexual AND Dysfunctions) OR (Sexual AND Disorders) OR (Sexual AND Disorder) OR "Sexual Dysfunctions" OR "Sexual Disorders" OR "Sexual Disorder" OR "Psychosexual Dysfunctions" OR (Dysfunction AND Psychosexual) OR (Dysfunctions AND Psychosexual) OR "Psychosexual Dysfunction" OR "Psychosexual Disorders" OR (Disorder AND Psychosexual) OR (Disorders AND Psychosexual) OR "Psychosexual Disorder" OR "Hypoactive Sexual Desire Disorder" OR "Sexual Aversion Disorder" OR (Aversion Disorders AND Sexual) OR (Disorders AND Sexual Aversion) OR "Sexual Aversion Disorders" OR "Orgasmic Disorder" OR (Disorders AND Orgasmic) OR "Orgasmic Disorders" OR "Sexual Arousal Disorder" OR (Arousal Disorders AND Sexual) OR (Disorders AND Sexual Arousal) OR "Sexual Arousal Disorders" OR "Frigidity"). RESULTS: We found 2150 articles by literature search, after deleting duplicates 1760 remained. Fifty-six articles remained for meta-analysis. The pooled prevalence of SD in MS patients estimated as 61% (95%CI:56-67%) (I2:95.7%, P < 0.001). The pooled prevalence of Anorgasmia in MS patients estimated as 29% (95%CI:20-39%) (I2:85.3%, P < 0.001). The pooled odds of developing SD in MS women estimated as 3.05(95%CI: 1.74-5.35) (I2:78.3%, P < 0.001). The pooled prevalence of decreased vaginal lubrication in MS patients estimated as 32%(95%CI:27-37%) (I2 = 94.2%, P < 0.001). The pooled prevalence of reduced libido was 48%(95%CI:36-61%) (I2:92.6%, P < 0.001). The pooled prevalence of arousal problems was 40%(95%CI: 26-54%) (I2:97.4%, P < 0.001). The pooled prevalence of intercourse satisfaction was 27% (95%CI: 8-46%) (I2:99%, P < 0.001). CONCLUSION: The result of this systematic review and meta-analysis show that the pooled prevalence of SD in women with MS is 61% and the odds of developing SD in comparison with controls is 3.05.

Human papillomavirus vaccination in low- and middle-income countries: progression, barriers, and future prospective.

Human papillomavirus (HPV) is a viral infection that, if does not go away, can cause health problems like genital warts and cancer. The national immunization schedules for individuals before sexual debut, significantly decreased HPV-associated mortality and it will be affordable. However, immunization programs remain vulnerable to macroeconomic factors such as inflation, fiscal policy, employment levels, and national income. This review aims to investigate the association between national income in lower-middle-income countries to explore recent advances and potential issues, as well as how to deal with challenges.

Low bone mineral density, a neglected condition in North Africa and Middle East: estimates from the Global Burden of Disease Study, 1990-2019.

Due to the high prevalence of low bone mineral density in North Africa and Middle East region, estimating its attributable burden would help to a better understanding of this neglected condition for policymakers and health researchers. This study presented the number of attributable deaths has doubled from 1990 to 2019. PURPOSE: This study provides the latest estimates of the burden of low bone mineral density (BMD) from 1990 to 2019 in North Africa and Middle East (NAME) region. METHODS: The data were extracted from the global burden of disease (GBD) 2019 study to estimate epidemiological indices such as deaths, disability-adjusted life years (DALYs), and summary exposure value (SEV). SEV is a measure of the exposure of the population to a risk factor that considers the amount of exposure by the level of risk. RESULTS: Our findings showed that in 1990-2019, the number of deaths and DALYs attributable to low BMD had almost doubled in the region and caused 20,371 (95% uncertainty intervals: 14,848-24,374) deaths and 805,959 (630,238-959,581) DALYs in 2019. However, DALYs and death rates showed a decreasing trend after age standardization. Saudi Arabia had the highest, and Lebanon had the lowest age-standardized DALYs rates in 2019, with rates of 434.2 (329.6-534.3) and 90.3 (70.6-112.1) per 100,000, respectively. The highest burden attributable to low BMD was in the 90-94 and over 95 age groups. Also, there was a decreasing trend in age-standardized SEV to low BMD for both sexes. CONCLUSION: Despite the decreasing trend of age-standardized burden indices, considerable amounts of deaths and DALYs were attributable to low BMD, especially in the elderly population, in the region in 2019. As the positive effects of proper interventions will be detectable in the long term, robust strategies and comprehensive stable policies are the ultimate solutions to achieving desired goals.

Global and regional quality of care index for prostate cancer: an analysis from the Global Burden of Disease study 1990-2019.

BACKGROUND: Prostate cancer (PCa) is one of the most prevalent cancers worldwide, with a significant burden on societies and healthcare providers. We aimed to develop a metric for PCa quality of care that could demonstrate the disease's status in different countries and regions (e.g., socio-demographic index (SDI) quintiles) and assist in improving healthcare policies. METHODS: Basic burden of disease indicators for various regions and age-groups were retrieved from Global Burden of Disease Study 1990-2019, which then were used to calculate four secondary indices: mortality to incidence ratio, DALYs to prevalence ratio, prevalence to incidence ratio, and YLLs to YLDs ratio. These four indices were combined through a principal component analysis (PCA), producing the quality of care index (QCI). RESULTS: PCa's age-standardized incidence rate increased from 34.1 in 1990 to 38.6 in 2019, while the age-standardized death rate decreased in the same period (18.1 to 15.3). From 1990 to 2019, global QCI increased from 74 to 84. Developed regions (high SDI) had the highest PCa QCIs in 2019 (95.99), while the lowest QCIs belonged to low SDI countries (28.67), mainly from Africa. QCI peaked in age groups 50 to 54, 55 to 59, or 65 to 69, depending on the socio-demographic index. CONCLUSIONS: Global PCa QCI stands at a relatively high value (84 in 2019). Low SDI countries are affected the most by PCa, mainly due to the lack of effective preventive and treatment methods in those regions. In many developed countries, QCI decreased or stopped rising after recommendations against routine PCa screening in the 2010-2012 period, highlighting the role of screening in reducing PCa burden.

Predicting Iran's achievement to Sustainable Development Goal 3.2: A systematic analysis of neonatal mortality with scenario-based projections to 2030.

BACKGROUND: Sustainable Development Goal 3.2 (SDG 3.2) is to reduce Under-5 and neonatal mortality rates (U5MR and NMR), two major health systems' performance indicators, globally by 2030. We aimed to report Iran's U5MR and NMR status during 2010-2017 and its achievement of SDG 3.2 by 2030, using scenario-based projection. STUDY DESIGN: To estimate the national and subnational levels of U5MR and NMR, we applied an Ensemble Bayesian Model Averaging (EBMA) with Gaussian Process Regression (GPR) and Spatio_temporal models. We used all available data sources including: 12-year data from the Death Registration System (DRS), two censuses, and a demographic and health surveys (DHS). This study employed two approaches, Maternal Age Cohort (MAC) and Maternal Age Period (MAP), to analyze summary birth history data obtained from censuses and DHS. In addition, we calculated the child mortality rate directly from DHS using the complete birth history method. National and subnational NMR was projected up to 2030 with a scenario-based method using average Annual Rate of Reduction (ARR) introduced by UN-IGME. RESULTS: In 2017, national U5MR and NMR were 15·2 (12·4-18·0) and 11·8 (10·4-13·2), with an average ARR of 5·1% (2·1-8·9) and 3·1% (0·9-5·8) during 2010-2017, respectively. According to our projection scenarios, 17 provinces have not fulfilled SDG 3.2 for NMR yet, and the current trend (the current trend of NMR improvement in Iran) will not result in reaching SDG for some provinces by 2030; However, if each province has the same neonatal mortality annual reduction rate as the best-performing province in the same region, besides achieving SDG, the national NMR will be reduced to 5·2, and almost 92,000 newborn lives will be saved. CONCLUSIONS: Iran has achieved SDG3.2 regarding U5MR and NMR; however, there are provincial inequalities. For all provinces to reach SDG3.2, health policies should focus on reducing provincial inequalities by precise planning for neonatal health care.

CNS demyelinating disease following inactivated or viral vector SARS-CoV-2 vaccines: A case series.

BACKGROUND: Several reports have been documented in possible association with the administration of different severe acute respiratory coronavirus 2 (SARS-CoV-2) vaccines and central nervous system (CNS)demyelinating disorders, specifically post mRNA vaccines. We report twelve cases of developing Multiple sclerosis (MS) or Neuromyelitis Optica spectrum disorders (NMOSD) following neither the first nor second dose of inactivated or viral vector COVID-19 vaccine. METHODS: We retrospectively compiled twelve patients' medical information with a new onset of MS or NMOSD in their first six weeks following a COVID-19 vaccine. RESULTS: We report twelve cases of MS (n = 9), clinically isolated syndrome (CIS)(n = 1), and NMOSD (n = 2) following COVID-19 inactivated vaccines (n = 11) or viral vector vaccines (n = 1), within some days following either the first (n = 3), second dose (n = 8), or third dose (n = 1). Their median age was 33.3 years, ranging from 19 to 53 years. Ten were women (83 %). All patients fully (n = 5) or partially (n = 2) recovered after receiving 3 doses of Corticosteroids. Common medications were Natalizumab, Teriflunomide, Dimethyl fumarate, and Rituximab. Also, Interferon beta 1-a was administered to one patient with severe symptoms of numbness. CONCLUSION: Our case series identifies the Sinopharm BBIBP-CorV and the AstraZeneca AZD1222 vaccines as potential triggers for CNS demyelinating diseases. Vaccine administration routines are not affected by these rare and coincidental events. However, these manifestations are not deniable and require serious attention. Further investigations are needed to clarify the actual mechanisms and real associations.

Prevalence of dysphagia in patients with multiple sclerosis: A systematic review and meta-analysis.

BACKGROUND: Dysphagia is a major disorder observed in patients with multiple sclerosis (MS), yet different prevalence rates are reported for it. Therefore, we designed this study to estimate the pooled prevalence of dysphagia in patients with MS. METHOD: We searched PubMed, Scopus, EMBASE, Web of Science, and gray literature including references from the identified studies, reviews studies, and conference abstracts which were published up to May 2022. Articles that were relevant to our topic and could provide information regarding the prevalence of dysphagia among MS patients were included; however, articles with self-report screening strategies were excluded. RESULTS: The literature search found 997 articles. After eliminating duplicates, 672 articles remained. Two conference abstracts were included for final analysis. A total of 11,266 MS cases and 5047 MS patients with dysphagia were included in the meta-analysis. The overall prevalence of dysphagia across all 54 studies was 44.8 % (95 % CI: [40.4 %-49.2 %]), with a high level of heterogeneity between countries (Q=; I2 = 94.96 %; p < 0.001). CONCLUSION: The results of this systematic review shows that the prevalence of dysphagia in MS patients is 45% which is greatly higher compared to the general population.

National and subnational burden of brain and central nervous system cancers in Iran, 1990-2019: Results from the global burden of disease study 2019.

INTRODUCTION: Central nervous system cancers (CNS cancers) impose a significant burden upon healthcare systems worldwide. Currently, the lack of a comprehensive study to assess various epidemiological indexes of CNS cancers on national and subnational scales in Iran can hamper healthcare planning and resource allocation in this regard. This study aims to fill this gap by providing estimates of CNS cancer epidemiological measures on national and subnational levels in Iran from 1990 to 2019. MATERIALS AND METHODS: This study is a part of Global Burden of Disease (GBD) 2019 that contains epidemiological measures including prevalence, incidence, mortality, Disability-Adjusted Life Years (DALYs), Years Lived with Disability (YLDs), and Years of Life Lost (YLLs) of CNS cancers. Age standardization was utilized for comparing different provinces. RESULTS: In 2019, 5811 (95% Uncertainty Interval: 2942-7046) national new cases and 3494 (1751-4173) deaths due to CNS cancers were reported. National age-standardized incidence (ASIR), deaths (ASDR), and DALYs rates were 7.3 (3.7-8.8), 4.6 (2.3-5.5), and 156.4 (82.0-187.0) per 100,000 in 2019, respectively. Subnational results revealed that ASDR and ASIR have increased in the past 30 years in all provinces. Although incidence rates have increased in all age groups and genders since 1990, death rates have remained the same for most age groups and genders except for young patients aged under 15, where a decrease in mortality and YLLs can be observed. CONCLUSION: The incidence, deaths, and DALYs of CNS cancers increased at national and subnational levels. These findings should be considered for planning and resource allocation.

The prevalence of restless legs syndrome (RLS) in patients with multiple sclerosis (MS): a systematic review and meta-analysis-an update.

INTRODUCTION: The prevalence of restless legs syndrome (RLS) is reported to vary in patients with multiple sclerosis (MS) in studies which are conducted in different populations. The goal of this systematic review and meta-analysis is to update the prevalence of RLS in MS cases. METHODS: We searched PubMed, Scopus, EMBASE, CINAHL, Web of Science, Google Scholar, and gray literature including references from identified studies and conference abstracts which were published up to June 2021. Data on the total number of participants, first author, country, disease duration, number of controls, mean patient age, male and female numbers, mean EDSS, and number of cases and/or controls with RLS were extracted from the included studies. RESULTS: The literature search revealed 855 articles; after deleting duplicates, 530 remained. For the meta-analysis, 75 studies were included (Fig. 1). In six articles, the authors did not differentiate between CIS and MS cases when reporting RLS cases. In total, 15,411 MS/CIS patients were evaluated and 4309 had RLS. The pooled prevalence of RLS was 28% (95% CI: 24-33%). The pooled prevalence of RLS in men was 22% (95% CI: 17-26%), and the pooled prevalence of RLS in women was 30% (95% CI: 25-35%). The pooled prevalence of RLS in controls was 8% (95% CI: 6-10%). CONCLUSION: The results of this systematic review and meta-analysis show that the pooled prevalence of RLS is 28% in MS cases and 8%. The pooled prevalence is higher in women than men (30% vs 22%).

Microbiomes and Pediatric onset multiple sclerosis (MS): A systematic review.

Background: Gut microbiomes play a role in developing and regulating autoimmune diseases such as multiple sclerosis (MS). We designed this systematic review to summarize the evidence of the effect of gut microbiota in developing pediatric-onset MS. Methods: PubMed, Scopus, EMBASE, Web of Science, Google Scholar, references of the references and conference abstracts were comprehensively searched by two independent researchers. The search was done on January 1st, 2023. Data regarding the total number of patients, the name of the first author, publication year, country of origin, mean age, duration of the disease, body mass index (BMI), type of MS, Expanded Disability Status Scale (EDSS), age at disease onset and stool composition were extracted. Results: A literature search revealed 4237 published studies. After removing duplicates, we had 2045 records for evaluation. Twenty-three full texts were evaluated, and four case-control studies remained for systematic review. Three studies were conducted in the United States and one in the Netherlands. The number of participants in included studies ranged between 24 and 68. The mean age of patients at the time of study varied between 11.9 and 17.9 years, and the mean age at the onset of the disease ranged between 11.5 and 14.3 years. Most included patients were female. The results show that median richness (the number of unique taxa identified, which was provided by two studies) was higher in controls, and also Margalef index, which was reported by one study was higher in control group than the case group. The results of two studies also demonstrated that median evenness indexes (taxon distribution, Shannon, Simpson) were higher in control groups, as well as PD index (Faith's phylogenic diversity metric). Conclusion: The result of this systematic review (including four studies) showed disruption of the microbiota-immune balance in pediatric-onset MS cases.

Is Celiac Disease (CD) Prevalent in Patients with Multiple Sclerosis (MS): A Systematic Review and Meta-Analysis.

Background: Celiac disease (CD) is an autoimmune disease, and its prevalence reported variously in different studies. The goal of this study is to evaluate the pooled prevalence of CD in subjects with MS. Methods: PubMed, Scopus, EMBASE, Web of Science, and Google Scholar along with gray literature were systematically searched. The search included all relevant studies which were published up to October 2022. Two researchers independently searched all databases and also references of included studies. Results: We found 8211 articles by literature search, and after deleting duplicates, 5594 remained. Fifteen articles remained for meta-analysis. Totally, 31418 patients were evaluated, and the total number of possible/confirmed cases was 124. Studies were published between 2004 and 2020, and the most published studies were from Italy. Five studies provided information regarding controls. The total number of controls was 22394, of whom 22 had CD. Mean age ranged from 35 to 55 years. The pooled prevalence of CD in MS patients was 0 (I 2 = 88.2%, p < 0.001). The pooled odds of CD in subjects with MS are 0.46 (95% CI: 0.19-1.1) (I 2 = 0, p = 0.9). Conclusion: The pooled prevalence of this systematic review showed that CD is not prevalent in MS cases.

Is elevated ALT associated with lifestyle risk factors? A population-based survey.

Purpose: Given the high prevalence of non-alcoholic fatty liver disease (NAFLD) and the role of Alanine aminotransferase (ALT) in diagnosing liver injury along with the increasing prevalence of lifestyle risk factors, we aimed to evaluate the association between serum ALT level and lifestyle risk factors in a population-based survey. Methods: This was a population-based study conducted in rural and urban areas of Iran in 2016. Cluster sampling method was applied to enroll a total of 31,050 participants aged ≥ 18. Demographic data, anthropometric measures, and laboratory samples were gathered. Multivariate logistic regression analyses were performed using three different cut-off levels for elevated ALT to assess the relationship between elevated ALT and lifestyle risk factors. Results: The prevalence of elevated ALT was significantly higher in men with elevated body mass index (BMI), waist-to-hip ratio (WTH), hip circumference, and salt consumption, likewise, in women with higher BMI and WTH. In the multivariate logistic model adjusted for age and sex, high WTH (adjusted odds ratio: 1.73; 95% CI 1.52-1.96), BMI > 25 (1.51; 95% CI 1.29-1.76), hip circumference (1.26; 95% CI 1-1.58), and current smoking (0.67; 95% CI 0.56-0.8) were associated with elevated ALT levels using American cut-off (ALT > 33U/L for male and ALT > 25U/L for female). Only physical measurements (BMI, WTH) but not lifestyle risk factors were related to the increased ALT regardless of the selected cut-offs. Conclusion: As elevated ALT was associated with several lifestyle risk factors, stewardship programs should be established to modify lifestyle risk factors, such as abdominal obesity and physical inactivity. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-022-01137-6.