Immune checkpoint inhibitors in gastrointestinal malignancies: an Umbrella review.

In the Modern era, immune checkpoint inhibitors (ICIs) have been the cornerstone of success in the treatment of several malignancies. Despite remarkable therapeutic advances, complex matrix together with significant molecular and immunological differences have led to conflicting outcomes of ICI therapy in gastrointestinal (GI) cancers. As far we are aware, to date, there has been no study to confirm the robustness of existing data, and this study is the first umbrella review to provide a more comprehensive picture about ICIs' efficacy and safety in GI malignancies. Systematic search on PubMed, Scopus, Web of Science, EMBASE, and Cochrane library identified 14 meta-analyses. The pooled analysis revealed that ICIs application, especially programmed death-1 (PD-1) inhibitors such as Camrelizumab and Sintilimab, could partially improve response rates in patients with GI cancers compared to conventional therapies. However, different GI cancer types did not experience the same efficacy; it seems that hepatocellular carcinoma (HCC) and esophageal cancer (EC) patients are likely better candidates for ICI therapy than GC and CRC patients. Furthermore, application of ICIs in a combined-modal strategy are perceived opportunity in GI cancers. We also assessed the correlation of PD-L1 expression as well as microsatellite status with the extent of the response to ICIs; overall, high expression of PD-L1 in GI cancers is associated with better response to ICIs, however, additional studies are required to precisely elaborate ICI responses with respect to microsatellite status in different GI tumors. Despite encouraging ICI efficacy in some GI cancers, a greater number of serious and fatal adverse events have been observed; further highlighting the fact that ICI therapy in GI cancers is not without cost, and further studies are required to utmost optimization of this approach in GI cancers.

Recent developments in SARS-CoV-2 vaccines: A systematic review of the current studies.

Designing and manufacturing efficient vaccines against coronavirus disease 2019 (COVID-19) is a major objective. In this systematic review, we aimed to evaluate the most important vaccines under construction worldwide, their efficiencies and clinical results in healthy individuals and in those with specific underlying diseases. We conducted a comprehensive search in PubMed, Scopus, EMBASE, and Web of Sciences by 1 December 2021 to identify published research studies. The inclusion criteria were publications that evaluated the immune responses and safety of COVID-19 vaccines in healthy individuals and in those with pre-existing diseases. We also searched the VAERS database to estimate the incidence of adverse events of special interest (AESI) post COVID-19 vaccination. Almost all investigated vaccines were well tolerated and developed good levels of both humoural and cellular responses. A protective and efficient humoural immune response develops after the second or third dose of vaccine and a longer interval (about 28 days) between the first and second injections of vaccine could induce higher antibody responses. The vaccines were less immunogenic in immunocompromised patients, particularly those with haematological malignancies. In addition, we found that venous and arterial thrombotic events, Bell's palsy, and myocarditis/pericarditis were the most common AESI. The results showed the potency of the SARS-CoV-2 vaccines to protect subjects against disease. The provision of further effective and safe vaccines is necessary in order to reach a high coverage of immunisation programs across the globe and to provide protection against infection itself.

Quercetin can be a more reliable treatment for metastatic prostate cancer than the localized disease: An in vitro study.

Quercetin is a plant flavonoid that has been recognized to have anti-inflammatory, antioxidant and anti-proliferative activities. This study aims to evaluate the inhibitory effects of quercetin against prostate malignancy in vitro and the underlying resistance mechanism. IC50 values of quercetin were determined by MTT assay. Annexin-V/PI staining was used to measure the rate of apoptosis. DNA cell cycle was analysed by PI staining method. Real-time PCR was performed to assess mRNA levels of OPN isoforms, VEGF isoforms, P53 and KLK2. Migration potential, proliferative capability and nucleus morphology of cells were evaluated by the scratch-wound assay, colony-forming assay and Hoechst staining, respectively. Quercetin significantly increased the apoptosis rate of PC-3 and LNCaP cell lines, arrested the cell cycle at the sub-G1/G1 phase, and reduced the migration potential and colony-forming capability. Moreover, upregulation of apoptosis-related genes and downregulation of genes involved in proliferation and angiogenesis was also observed. Although our results elucidated that quercetin has antitumor effects on PC-3 and LNCaP, for the first time, we showed that quercetin treatment causes alterations in the expression of OPN and VEGF isoforms, which are cancer-promoting modulators through various processes such as angiogenesis and drug-resistance. Prostate malignant cells can dodge the anti-carcinogenic properties of quercetin via modulation of OPN and VEGF isoforms in vitro. Therefore, quercetin acts as a double-edged sword in prostate cancer treatment.

Clostridioides difficile PCR ribotypes 001 and 084 can trigger autophagy process in human intestinal Caco-2 cells.

Autophagy is a homeostatic process that can promote cell survival or death. However, the exact role of autophagy in Clostridioides difficile infection (CDI) is still not precisely elucidated. Here, we investigate the role of distinct C. difficile ribotypes (RTs) in autophagy induction using Caco-2 cells. The expression analysis of autophagy-associated genes and related miRNAs were examined following treatment of Caco-2 cells with C. difficile after 4 and 8 h using RT-qPCR. Toxin production was assessed using enzyme-linked immunosorbent assay (ELISA). Immunofluorescence analysis was performed to detect MAP1LC3B/LC3B, followed by an autophagic flux analysis. C. difficile significantly reduced the viability of Caco-2 cells in comparison with untreated cells. Elevated levels of LC3-II and SQSTM1/p62 by C. difficile RT001 and RT084 in the presence of E64d/leupeptin confirmed the induction of autophagy activity. Similarly, the immunofluorescence analysis demonstrated that C. difficile RT001 and RT084 significantly increased the amount of LC3-positive structures in Caco-2 cells. The induction of autophagy was further demonstrated by increased levels of LC3B, ULK1, ATG12, PIK3C3/VPS34, BECN1 (beclin 1), ATG5, and ATG16L1 transcripts and reduced levels of AKT and MTOR gene expression. The expression levels of MIR21 and MIR30B, microRNAs that suppress autophagy, were differentially affected by C. difficile. In conclusion, the present work revealed that C. difficile bacteria can induce autophagy through both toxin-dependent and -independent mechanisms. Also, our results suggest the potential role of other C. difficile virulence factors in autophagy modulation using intestinal cells in vitro.

Association between human herpesviruses and multiple sclerosis: A systematic review and meta-analysis.

AIM: The aim of this study was to investigate the prevalence and potential association between infection with different herpes viruses and multiple sclerosis (MS). METHODS: A systematic literature search was performed by finding relevant cross-sectional and case-control studies from a large online database. Heterogeneity, Odds ratio (OR), and corresponding 95% Confidence interval (CI) were applied to all studies by meta-analysis and forest plots. The analysis was performed using Stata Software v.14. RESULTS: One hundred and thirty-four articles (289 datasets) were included in the meta-analysis, 128 (245 datasets) of which were case/control and the rest were cross-sectional. The pooled prevalence of all human herpes viruses among MS patients was 50% (95% CI: 45-55%; I2 = 96.91%). In subgroup analysis, the pooled prevalence of Herpes simplex virus (HSV), Varicella-zoster virus (VZV), Epstein-Barr virus (EBV), Cytomegalovirus (CMV), Human herpes virus 6 (HHV-6), Human herpes virus 7 (HHV-7), and Human herpes virus 8 (HHV-8) was 32%, 52%, 74%, 41%, 39% 28%, and 28%, respectively. An association was found between infection with human herpes viruses and MS [summary OR 2.07 (95% CI (1.80-2.37); I2 = 80%)]. CONCLUSION: The results of the present study showed that EBV, VZV, and HHV-6 infection are associated with multiple sclerosis and can be considered as potential risk factors for MS. Although the exact molecular mechanism of the role of herpes viruses in the development of MS is still unknown, it seems that molecular mimicry, the release of autoreactive antibodies, and inflammation in the CNS following viral infection can be important factors in the induction of MS.

Safety and efficacy of T-cell-redirecting bispecific antibodies for patients with multiple myeloma: a systematic review and meta-analysis.

BACKGROUND: In recent years, several bispecific antibodies (BsAbs) have been introduced that revolutionized the treatment approach for patients with multiple myeloma (MM). In the present study, we sought for conducting a systematic review and meta-analysis with the aim of evaluating the safety and efficacy of BsAbs in MM patients. METHODS: PubMed, Scopus, Web of Science, and Embase databases were systematically searched on June 10, 2022. Two steps of title/abstract and full-text screening were performed for selecting the relevant articles. The primary endpoint was considered to evaluate the safety of BsAbs by examining the rate of hematologic and non-hematologic adverse effects (AEs). The secondary outcome was set at the efficacy of BsAbs through pooling objective response rate (ORR), (stringent) complete response (sCR/CR), very good partial response (VGPR), and partial response (PR). RESULTS: Eleven publications with a total of nine evaluable BsAbs were included for qualitative and quantitative data synthesis. Hematologic AEs were more common among patients than non-hematologic events, with the most frequent events being anemia (41.4%), neutropenia (36.4%), and thrombocytopenia (26.3%). The most common non-hematological AE was infection, which occurred in 39.9% of patients, followed by dysgeusia (28.3%), fatigue (26.5%), and diarrhea (25.8%). Besides, 8.1% of patients experienced immune effector cell-associated neurotoxicity syndrome and neurotoxicity occurred in 5.1% of them. Moreover, 59.8% of patients experienced cytokine release syndrome. The pooled rate of deaths attributable to BsAbs was estimated at 0.1%. In terms of efficacy measures, the ORR was achieved in 62.6% of MM patients, and the pooled rates of sCR/CR, VGPR, and PR were 22.7%, 23.0%, and 12.1%, respectively. CONCLUSIONS: In an era with several emerging promising treatments for MM, BsAbs have achieved a high ORR and tolerable AEs in heavily pretreated patients. However, there is still room for developing BsAbs with a lower rate of AEs and capable of bypassing tumor evasion mechanisms.

The relationship between blood groups and risk of infection with SARS-CoV-2 or development of severe outcomes: A review.

The outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is considered a global catastrophe that has overwhelmed health care systems. Since initiation of the pandemic, identification of characteristics that might influence risk of infection and poor disease outcomes have been of paramount interest. Blood group phenotypes are genetically inherited characteristics whose association with certain infectious diseases have long been debated. The aim of this review is to identify whether a certain type of blood group may influence an individual's susceptibility to SARS-CoV-2 infection and developing severe outcomes. Our review shows that blood group O protects individuals against SARS-CoV-2, whereas blood group A predisposes them to being infected. Although the association between blood groups and outcomes of COVID-19 is not consistent, it is speculated that non-O blood group carriers with COVID-19 are at higher risk of developing severe outcomes in comparison to O blood group. The interaction between blood groups and SARS-CoV-2 infection is hypothesized to be as result of natural antibodies against blood group antigens that may act as a part of innate immune response to neutralize viral particles. Alternatively, blood group antigens could serve as additional receptors for the virus and individuals who are capable of expressing these antigens on epithelial cells, which are known as secretors, would then have a high propensity to be affected by SARS-CoV-2.

Potency of BNT162b2 and mRNA-1273 vaccine-induced neutralizing antibodies against severe acute respiratory syndrome-CoV-2 variants of concern: A systematic review of in vitro studies.

BNT162b2 and mRNA-1273 are two types of mRNA-based vaccine platforms that have received emergency use authorization. The emergence of novel severe acute respiratory syndrome (SARS-CoV-2) variants has raised concerns of reduced sensitivity to neutralization by their elicited antibodies. We aimed to systematically review the most recent in vitro studies evaluating the effectiveness of BNT162b2 and mRNA-1273 induced neutralizing antibodies against SARS-CoV-2 variants of concern. We searched PubMed, Scopus, and Web of Science in addition to bioRxiv and medRxiv with terms including 'SARS-CoV-2', 'BNT162b2', 'mRNA-1273', and 'neutralizing antibody' up to June 29, 2021. A modified version of the Consolidated Standards of Reporting Trials (CONSORT) checklist was used for assessing included study quality. A total 36 in vitro studies meeting the eligibility criteria were included in this systematic review. B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), and B.1.617.2 (Delta) are four SARS-CoV-2 variants that have recently been identified as variants of concern. Included studies implemented different methods regarding pseudovirus or live virus neutralization assays for measuring neutralization titres against utilized viruses. After two dose vaccination by BNT162b2 or mRNA-1273, the B.1.351 variant had the least sensitivity to neutralizing antibodies, while B.1.1.7 variant had the most sensitivity; that is, it was better neutralized relative to the comparator strain. P.1 and B.1.617.2 variants had an intermediate level of impaired naturalization activity of antibodies elicited by prior vaccination. Our review suggests that immune sera derived from vaccinated individuals might show reduced protection of individuals immunized with mRNA vaccines against more recent SARS-CoV-2 variants of concern.

Epidemiology, prognosis and management of potassium disorders in Covid-19.

Coronavirus disease (Covid-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently the largest health crisis facing most countries. Several factors have been linked with a poor prognosis for this disease, including demographic factors, pre-existing comorbidities and laboratory parameters such as white blood cell count, D-dimer, C-reactive protein, albumin, lactate dehydrogenase, creatinine and electrolytes. Electrolyte abnormalities particularly potassium disorders are common among Covid-19 patients. Based on our pooled analysis, hypokalemia and hyperkalemia occur in 24.3% and 4.15% of Covid-19 patients, respectively. Potassium level deviation from the normal range may increase the chances of unfavorable outcomes and even death. Therefore, this article reviewed the epidemiology of potassium disorders and explained how hypokalemia and hyperkalemia are capable of deteriorating cardiac outcomes and the prognosis of Covid-19 for infected patients. The article finishes by highlighting some important considerations in the management of hypokalemia and hyperkalemia in these patients.

ABO blood groups and risk of human immunodeficiency virus infection: A systematic review and meta-analysis.

The last few decades have seen a pandemic of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), which continues to cause substantial morbidity and mortality. ABO blood groups are anthropological and genetic characteristics of a population whose associations with HIV infection are still controversial. This systematic review with meta-analysis was undertaken to investigate whether certain blood groups may have associations with HIV infection. PubMed, Scopus and Web of Science databases were systematically searched as of 6 September 2021. Grey literature was identified through screening Google Scholar, and reference lists of relevant studies. All observational studies providing data on ABO blood group distribution among HIV-infected and uninfected participants were included. Using a random effect model, risk ratios (RR) and 95% confidence intervals (CIs) were pooled to quantify this relationship. Fifty eligible studies with a total of 3,068,244 participants and 6508 HIV-infected cases were included. The overall analysis found that blood group AB increased the risk of HIV infection by 19% as compared with non-AB blood groups (RR = 1.19, 95% CI: 1.03-1.39, p = 0.02). Pooled estimates for other blood groups failed to reach statistical significance. Subgroup analyses identified a positive relationship between AB blood group and HIV infection within Asia, patient populations (as opposed to blood donors and general populations), studies with lower sample sizes, high-income countries and studies with a moderate quality score. The sequential omission and re-analysis of studies within sensitivity analyses produced no change in the overall pooled effect. In conclusion, this study identified that blood group AB carriers were more susceptible to HIV infection. Future investigations should be directed toward clarification of the exact role of ABO blood groups in HIV infection and the possible underlying mechanisms.

Cardiac complications following mRNA COVID-19 vaccines: A systematic review of case reports and case series.

There have been several local and systemic adverse events associated with mRNA COVID-19 vaccines. Pericarditis, myocarditis and myocardial infarction are examples of cardiac complications related to these vaccines. In this article, we conducted a systematic review of case reports and case series to identify the clinical profile, investigations, and management of reported cardiac complications post-mRNA COVID-19 vaccines. We systematically searched PubMed, Scopus, Web of Science, and Google Scholar, as well as the medRxiv preprint server, with terms including: 'SARS-CoV-2', 'COVID-19', 'messenger RNA vaccine*', 'mRNA-1273 vaccine', 'BNT162 vaccine', 'myocarditis', 'pericarditis', 'stroke' and 'Myocardial Ischemia' up to 25 September 2021. Studies were excluded if they were not case reports or case series, or reported cases from non-mRNA vaccines. Case reports and case series were included that investigated the potential cardiac complications associated with mRNA COVID-19 vaccines. The JBI checklist was used to assess quality and data synthesis was conducted using a qualitative methodology called narrative synthesis. Sixty-nine studies, including 43 case reports and 26 case series, were included. Myocarditis/myopericarditis and pericarditis were the most common adverse events among the 243 reported cardiac complications, post mRNA COVID-19 vaccination. Males with a median age of 21 years had the highest frequency of myocarditis. Almost three quarters (74.4%) of cases with myocarditis had received the BNT162b2 vaccine and 87.7% had received the second dose of the vaccine. Chest pain (96.1%) and fever (38.2%) were the most common presentations. CK-MB, troponin, and NT-proBNP were elevated in 100%, 99.5% and 78.3% of subjects, respectively. ST-segment abnormality was the most common electrocardiogram feature. Cardiac magnetic resonance imaging, which is the gold-standard approach for diagnosing myocarditis, was abnormal in all patients diagnosed with myocarditis. Non-steroidal anti-inflammatory drugs were the most prescribed medication for the management of myocarditis. Apart from inflammatory conditions, some rare cases of Takotsubo cardiomyopathy, myocardial infarction, myocardial infarction with non-obstructive coronary arteries, and isolated tachycardia were also reported following immunisation with mRNA COVID-19 vaccines. We acknowledge that only reviewing case reports and case series studies is one potential limitation of our study. We found that myocarditis was the most commonly reported adverse cardiac event associated with mRNA COVID-19 vaccines, which presented as chest pain with a rise in cardiac biomarkers. Further large-scale observational studies are recommended.

Efficacy of tocilizumab in the treatment of COVID-19: An umbrella review.

Tocilizumab is an interleukin (IL)-6 receptor inhibitor that has been proposed as a therapeutic agent for treating coronavirus disease 2019 (COVID-19). The aim of this umbrella review was to determine the efficacy of tocilizumab in treating COVID-19, and to provide an overview of all systematic reviews on this topic. We systematically searched PubMed, Scopus, the Web of Science collection, the Cochrane library, Epistemonikos, and Google Scholar, as well as the medRxiv preprint server. These databases were searched up to 30 September 2021, using the following keywords: 'SARS-CoV-2', 'COVID-19', 'tocilizumab', 'RHPM-1', 'systematic review', and 'meta-analysis'. Studies were included if they were systematic reviews (with or without meta-analysis) investigating the efficacy or safety of tocilizumab in confirmed COVID-19 patients. The AMSTAR 2 checklist was used to assess quality of the included articles, while publication bias was examined using Egger's test. A total of 50 eligible systematic reviews were included. The pooled estimates showed significant reductions in clinical failure (risk ratio (RR) 0.75; 95% confidence interval (CI), 0.61-0.93), deaths (RR 0.78; 95%CI, 0.71-0.85) and the need for mechanical ventilation (RR 0.77; 95%CI, 0.64-0.92) for those receiving tocilizumab compared with the control group. Also, an emerging survival benefit was demonstrated for those who received tocilizumab, over those in the control group (adjusted hazard ratio (aHR) 0.52; 95%CI, 0.43-0.63). In addition, tocilizumab substantially increased the number of ventilator-free days, compared with the control treatments (weighted mean difference (WMD) 3.38; 95%CI, 0.51-6.25). Furthermore, lymphocyte count (WMD 0.26 × 109 /L; 95%CI, 0.14-0.37), IL-6 (WMD 176.99 pg/mL; 95%CI, 76.34-277.64) and D-dimer (WMD 741.08 ng/mL; 95%CI, 109.42-1372.75) were all significantly elevated in those receiving tocilizumab. However, the level of lactate dehydrogenase (LDH) (WMD -30.88 U/L; 95%CI, -51.52, -10.24) and C-reactive protein (CRP) (WMD -104.83 mg/L; 95%CI, -133.21, -76.46) were both significantly lower after treatment with tocilizumab. Tocilizumab treatment reduced the risk of intubation, mortality and the length of hospital stay, without increasing the risk of superimposed infections in COVID-19 patients. Therefore, tocilizumab can be considered an effective therapeutic agent for treating patients with COVID-19.

The burden of pancreatic cancer and its attributable risk factors in the Middle East and North Africa region, 1990-2019.

BACKGROUND AND AIM: Globally, pancreatic cancer is recognized as one of the most lethal types of cancers. We report the burden of pancreatic cancer and its attributable risk factors in the Middle East and North Africa (MENA) region, from 1990 to 2019, by age, sex, and socio-demographic index. METHODS: Publicly available data from the Global Burden of Disease 2019 study were used to report the incidence, deaths, and disability-adjusted life years (DALYs) attributable to pancreatic cancer, as counts and age-standardized rates with 95% uncertainty intervals. RESULTS: In 2019, pancreatic cancer had an age-standardized incidence rate of 5.3 and a death rate of 5.5 (per 100 000) in MENA, which have increased by 97.5% and 93.4%, respectively, since 1990. There were 563.6 thousand DALYs attributable to pancreatic cancer in 2019, with an age-standardized DALY rate of 123.0, which has increased by 84.9% since 1990. The highest number of incident cases was found in the 60-64 and 65-69 age groups, among male and female, respectively. In addition, the MENA/global DALY ratios were higher in all age groups for both sexes in 2019, than they were in 1990. There was a positive association between socio-demographic index and the burden of pancreatic cancer. Smoking, high fasting plasma glucose, and high body mass index were responsible for 19.2%, 9.3%, and 9.3% of the attributable DALYs in 2019, respectively. CONCLUSIONS: There was a clear and substantial increase in the burden of pancreatic cancer in the MENA region. Prevention programs should be implemented in the region that target these three risk factors.

The burden of Alzheimer's disease and other types of dementia in the Middle East and North Africa region, 1990-2019.

BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia and this progressive neurological disorder is associated with substantial mortality and morbidity. We aimed to report the burden of AD and other types of dementia in the Middle East and North Africa (MENA) region, by age, sex and sociodemographic index (SDI), for the period 1990-2019. METHODS: publicly accessible data on the prevalence, death and disability-adjusted life years (DALYs) because of AD, and other types of dementia, were retrieved from the global burden of disease 2019 project for all MENA countries from 1990 to 2019. RESULTS: in 2019, the age-standardised point prevalence of dementia was 777.6 per 100,000 populations in MENA, which was 3.0% higher than in 1990. The age-standardised death and DALY rates of dementia were 25.5 and 387.0 per 100,000, respectively. In 2019, the highest DALY rate was observed in Afghanistan and the lowest rate was in Egypt. That same year, the age-standardised point prevalence, death and DALY rates increased with advancing age and were higher for females of all age groups. From 1990 to 2019, the DALY rate of dementia decreased with increasing SDI up to 0.4, then slightly increased up to an SDI of 0.75, followed by a decrease for the remaining SDI levels. CONCLUSIONS: the point prevalence of AD and other types of dementia has increased over the past three decades, and in 2019, the corresponding regional burden was higher than the global average.

The estimated burden of bulimia nervosa in the Middle East and North Africa region, 1990-2019.

OBJECTIVE: We aimed to report the burden of bulimia nervosa (BN) in the Middle East and North Africa (MENA) region by age, sex, and sociodemographic index (SDI), for the period 1990-2019. METHODS: Estimates of the prevalence, incidence, and disability-adjusted life-years (DALYs) attributable to BN were retrieved from the Global Burden of Disease study 2019, between 1990 and 2019, for the 21 countries in the MENA region. The counts and age-standardized rates (per 100,000) were presented, along with their corresponding 95% uncertainty intervals. RESULTS: In 2019, the estimated regional age-standardized point prevalence and incidence rates of BN were 168.3 (115.0-229.6) and 178.6 (117.0-255.6) per 100,000, which represented 22.0% (17.5-27.2) and 10.4% (7.1-14.7) increases, respectively, since 1990. Moreover, in 2019 the regional age-standardized DALY rate was 35.5 (20.6-55.5) per 100,000, which was 22.2% (16.7-28.2) higher than in 1990. In 2019, Qatar (58.6 [34.3-92.5]) and Afghanistan (18.4 [10.6-29.2]) had the highest and lowest age-standardized DALY rates, respectively. Regionally, the age-standardized point prevalence of BN peaked in the 30-34 age group and was more prevalent among women. In addition, there was a generally positive association between SDI and the burden of BN across the measurement period. DISCUSSION: In the MENA region, the burden of BN has increased over the last three decades. Cost-effective preventive measures are needed in the region, especially in the high SDI countries. PUBLIC SIGNIFICANCE: This study reports the estimated burden of BN in the MENA region and shows that its burden has increased over the last three decades.

The burden of Parkinson's disease in the Middle East and North Africa region, 1990-2019: results from the global burden of disease study 2019.

BACKGROUND: Parkinson's disease (PD) remains a common disabling progressive neurodegenerative disorder. We aimed to report the prevalence, death and disability-adjusted life-years (DALYs) attributable to PD in the Middle East and North Africa (MENA) region and its 21 countries by age, sex and socio-demographic index (SDI), between 1990 and 2019. METHODS: Publicly available data on the burden of PD in the MENA countries were retrieved from the Global Burden of Disease (GBD) 2019 project. The results are presented with age-standardised numbers and rates per 100,000 population, along with their corresponding 95% uncertainty intervals (UIs). RESULTS: In 2019, PD had an age-standardised point prevalence of 82.6 per 100,000 population in MENA and an age-standardised death rate of 5.3, which have increased from 1990 to 2019 by 15.4% and 2.3%, respectively. In 2019, the age-standardised DALY rate of PD was 84.4, which was 0.9% higher than in 1990. The highest and lowest age-standardised DALY rates of PD in 2019 were found in Qatar and Kuwait, respectively. Also in 2019, the highest number of prevalent cases and number of DALYs were found in the 75-79 age group for both sexes. In 2019, females in MENA had an overall higher DALY rate. Furthermore, from 1990 to 2019 the burden of PD generally decreased with increasing socio-economic development, up to an SDI of around 0.4, and then increased with higher levels of SDI. CONCLUSION: An upward trend was observed in the point prevalence of PD over the last three decades. This highlights the need to allocate more resources for research. Furthermore, properly equipped healthcare services are needed for the increasing number of patients with PD.

The burden of low back pain and its association with socio-demographic variables in the Middle East and North Africa region, 1990-2019.

BACKGROUND: Low back pain (LBP) is the most common musculoskeletal disorder globally. Providing region- and national-specific information on the burden of low back pain is critical for local healthcare policy makers. The present study aimed to report, compare, and contextualize the prevalence, incidence and years lived with disability (YLDs) of low back pain in the Middle East and North Africa (MENA) region by age, sex and sociodemographic index (SDI), from 1990 to 2019. METHODS: Publicly available data were obtained from the Global Burden of Disease (GBD) study 2019. The burden of LBP was reported for the 21 countries located in the MENA region, from 1990 to 2019. All estimates were reported as counts and age-standardised rates per 100,000 population, together with their corresponding 95% uncertainty intervals (UIs). RESULTS: In 2019, the age-standardised point prevalence and incidence rate per 100,000 in MENA were 7668.2 (95% UI 6798.0 to 8363.3) and 3215.9 (95%CI 2838.8 to 3638.3), which were 5.8% (4.3 to 7.4) and 4.4% (3.4 to 5.5) lower than in 1990, respectively. Furthermore, the regional age-standardised YLD rate in 2019 was 862.0 (605.5 to 1153.3) per 100,000, which was 6.0% (4.2 to 7.7) lower than in 1990. In 2019, Turkey [953.6 (671.3 to 1283.5)] and Lebanon [727.2 (511.5 to 966.0)] had the highest and lowest age-standardised YLD rates, respectively. There was no country in the MENA region that showed increases in the age-standardised prevalence, incidence or YLD rates of LBP over the measurement period. Furthermore, in 2019 the number of prevalent cases were highest in the 35-39 age group, with males having a higher number of cases in all age groups. In addition, the age-standardised YLD rates for males in the MENA region were higher than the global estimates in almost all age groups, in both 1990 and 2019. Furthermore, the burden of LBP was not associated with the level of socio-economic development during the measurement period. CONCLUSION: The burden attributable to LBP in the MENA region decreased slightly from 1990 to 2019. Furthermore, the burden among males was higher than the global average. Consequently, more integrated healthcare interventions are needed to more effectively alleviate the burden of low back pain in this region.

The burden of major depressive disorder in the Middle East and North Africa region, 1990-2019.

BACKGROUND: Major depressive disorder (MDD) is one of the leading causes of disability. We aimed to report the MDD-attributable prevalence, incidence and years lived with disability (YLDs) in the Middle East and North Africa (MENA) region from 1990 to 2019 by age, sex and socio-demographic index (SDI). METHODS: Publicly available data on the burden of MDD were retrieved from the Global Burden of Disease (GBD) study 2019 for the 21 countries in MENA. The counts and age-standardised rates (per 100,000) were presented, along with their corresponding 95% uncertainty intervals. RESULTS: In 2019, MDD had an age-standardised point prevalence of 3322.1 and an incidence rate of 4921.7 per 100,000 population in MENA. Furthermore, there were 4.1 million YLDs in 2019. However, there were no substantial changes in the MDD burden over the period 1990-2019. In 2019, Palestine had the highest burden of MDD. The highest prevalence, incidence and YLDs attributable to MDD were found in the 35-39 age group. In 2019, the YLD rate in MENA was higher than the global rate for almost all age groups. Furthermore, there was a broadly negative association between the YLD rate and SDI. CONCLUSION: The study highlights the need to prevent the disorder using a multidisciplinary approach and for the provision of cost-effective treatments for those affected, in order to increase their quality of life.

Surface layer protein A from hypervirulent Clostridioides difficile ribotypes induce significant changes in the gene expression of tight junctions and inflammatory response in human intestinal epithelial cells.

BACKGROUND: Surface layer protein A (SlpA), the primary outermost structure of Clostridioides difficile, plays an essential role in C. difficile pathogenesis, although its interaction with host intestinal cells are yet to be understood. The aim of this study was to investigate the effects of SlpA extracted from C. difficile on tight junction (TJ) proteins expression and induction of pro-inflammatory cytokines in human colon carcinoma cell line HT-29. SlpA was extracted from three toxigenic C. difficile clinical strains including RT126, RT001, RT084 as well as C. difficile ATCC 700057 as non-toxigenic strain. Cell viability was performed by MTT assay, and the mRNA expression of TJ proteins and inflammation-associated genes was determined using quantitative RT-PCR. Additionally, the secretion of IL-8, IL-1ß and TNF-α cytokines was measured by ELISA. RESULTS: C. difficile SlpA from selected RTs variably downregulated the expression level of TJs-assassinated genes and increased the expression level of TLR-4 and pro-inflammatory cytokines in HT-29 treated cells. SlpA from RT126 significantly (padj<0.05) decreased the gene expression level of claudins family and JAM-A and increased the secretion of IL-8, TNF-α and IL1-ß as compared to untreated cells. Moreover, only SlpA from RT001 could significantly induce the expression of IL-6 (padj<0.05). CONCLUSION: The results of the present study highlighted the importance of SlpA in the pathogenesis of CDI and C. difficile-induced inflammatory response in the gut. Further studies are required to unravel the significance of the observed results in promoting the intestinal inflammation and immune response induced by C. difficile SlpA from different RTs.

Prevalence, incidence and years lived with disability due to polycystic ovary syndrome in 204 countries and territories, 1990-2019.

STUDY QUESTION: What is the global, regional and national burden of polycystic ovary syndrome (PCOS), by age and socio-demographic index (SDI), over the period 1990-2019? SUMMARY ANSWER: In 2019, the global age-standardized point prevalence, incidence and years lived with disability (YLD) of PCOS were 30.4, 29.5 and 29.9 per 100 000 population, respectively. WHAT IS KNOWN ALREADY: Data from the Global Burden of Disease (GBD) study 2017 showed that the global age-standardized PCOS incidence rate increased 1.45% over the period 1990-2017. STUDY DESIGN, SIZE, DURATION: A systematic analysis of the PCOS prevalence, incidence and YLDs across 204 countries and territories was performed. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data on the point prevalence, annual incidence and YLDs due to PCOS were retrieved from the GBD study 2019 for 204 countries and territories from 1990 to 2019. The counts and age-standardized rates (per 100 000) are presented, along with their corresponding 95% uncertainty intervals (UIs). MAIN RESULTS AND THE ROLE OF CHANCE: In 2019, the global age-standardized point prevalence and annual incidence rates for PCOS were 1677.8 (95% UI: 1166.0 to 2192.4) and 59.8 (95% UI: 41.7 to 78.9) per 100 000, which represents a 30.4% and 29.5% increase since 1990, respectively. Moreover, the global age-standardized YLD rate in 2019 was 14.7 (6.3-29.5), an increase of 29.9% since 1990. In 2019, Italy (7897.0), Japan (6298.7) and New Zealand (5419.1) had the highest estimated age-standardized point prevalences of PCOS. Globally, the number of prevalent cases and the point prevalence of PCOS peaked in the 25-29 years and 40-44 years age groups, respectively. Positive associations were found between the burden of PCOS and the SDI at the regional and national levels. LIMITATIONS, REASONS FOR CAUTION: Variations in how PCOS was defined is a major limitation that prevents valid comparisons between different regions. WIDER IMPLICATIONS OF THE FINDINGS: Globally, the burden of PCOS has increased at an alarming rate, making it a major public health concern. Increasing public awareness about this common condition, improving management options and increasing support to reduce factors which lead to further complications, need to be public health priorities. STUDY FUNDING/COMPETING INTEREST(S): The Bill and Melinda Gates Foundation, who were not involved in any way in the preparation of this manuscript, funded the GBD study. The Shahid Beheshti University of Medical Sciences, Tehran, Iran (Grant No. 28709) also supported the present report. The authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.