West syndrome (WS) is a severe developmental and epileptic encephalopathy of infancy, defined by the triad of epileptic spasms, hypsarrhythmic electroencephalography, and developmental delay. Recent limited studies have suggested that the RYR3 gene is involved in the pathogenesis of WS. Our study presents an Iranian patient with WS and aims to provide further evidence to support the role of RYR3 variants in this condition. The proband was a male patient aged 2 years and 2 months with drug-resistant epileptic spasms and developmental regression. Trio-based whole-exome sequencing (Trio-WES) was conducted, and a novel de novo heterozygous variant in RYR3 (NM_001036.6: c.4112T>C, p.Leu1371Pro) was identified in the proband. The variant was not found in population databases, and bioinformatics analyses also predicted the deleterious impact of the variant. This study describes a novel RYR3 variant in a patient with WS, supporting a potential pathogenic role for RYR3 in early-onset epileptic encephalopathy. Therefore, it should be considered during the genetic assessment of unexplained WS cases.
In the article titled "Latent Trajectories and Regional Differences in Carbon Monoxide Mortality Across Provinces of Iran," published in Arch Iran Med. August 2025;28(8):432-442(doi:10.34172/aim.34565), the affiliation of Seyed Saeed Hashemi Nazari should be updated to the following: Air Quality and Climate Change Research Center, Research Institute for Health Sciences and Environment, Shahid Beheshti University of Medical Sciences, Tehran. This correction has now been updated in both the PDF and HTML versions of the article.
Gastrointestinal cancers encompass a range of malignancies, including esophageal, gastric, esophagogastric, hepatocellular, pancreatic, and intestinal cancers. Considering the prevalence of these cancers, alongside their fatal nature, and the nonspecific symptoms that often arise in the advanced stages, developing a non-invasive screening/diagnostic method capable of detecting cancer early is in high demand. Exhaled breath serves as an accessible source of biomarkers, including volatile organic compounds (VOCs), a promising type of diagnostic marker. This method requires a sample as small as five breaths. Exhaled breath analysis is conducted using different mass spectrometry methods coupled with nano sensors or neural networks. Furthermore, innovative devices like electronic noses have also shown great promise in diagnosing different types of cancers. These biomarkers show potential in reliably differentiating between healthy individuals and cancer patients. Additionally, these compounds can be utilized for cancer staging and monitoring treatment response. However, certain fallbacks persist in differentiating malignant from pre-malignant conditions. Despite the promise of this diagnostic approach, certain limitations, such as variations in VOC profiles across different populations, lack of standardized collection protocols, and absence of established universal reference standards, underscore the need for proper standardization and large-scale, multi-center validation studies.
Introduction: Cerebrovascular disorders (CeVDs) are among the leading causes of death worldwide. This study aims to analyze the trends in mortality due to CeVDs in northern Iran between 2016 and 2023. Methods: In this cross-sectional study, we included all documented Deaths due to CeVDs in Babol County, north of Iran, from 2016 to 2023. The crude mortality rate (CMR) and age-standardized mortality rate (ASMR) were used to assess the trends in CeVDs mortality. The Cochran-Armitage trend test and Joinpoint regression were employed to analyze the changes in disease trends. Results: During the study period, a total of 1,798 deaths from CeVDs were reported, with a mean age of 76.8±13.2 years. The CMR and ASMR for CeVDs decreased from 38.4 and 28.3 per 100,000 population in 2016 to 30.9 and 23.3 per 100,000 in 2023 (P<0.001). The trend decreased in both genders and urban and rural populations (P<0.05). Joinpoint regression indicated a break point in 2018. Between 2018 and 2023, the ASMR trend decreased, with an annual percentage change of -7.98% (95% CI, -18.72% to -4.88%). Conclusion: This study reveals a significant decrease in CeVDs mortality in the region, indicating progress in therapeutic interventions. However, death rates in rural areas remain high. Addressing this condition requires targeted approaches and increased resource allocation.
Asthma in older adults represents a growing and underrecognized clinical challenge, characterized by increased morbidity, mortality, and complex immunological alterations associated with aging. Although the global literature on asthma immunopathogenesis continues to expand rapidly, particularly in the areas of immunosenescence, inflammaging, and biomarker discovery, a focused synthesis of innate immune mechanisms specific to older populations remains limited. Epidemiological data indicate that asthma prevalence in individuals aged≥60 years ranges from 4% to 13%, yet this group accounts for a disproportionate share of asthma-related mortality. Age-associated physiological changes, comorbidities, and frequent underdiagnosis contribute to poorer outcomes. Emerging evidence from academic research centers highlights profound age-related alterations in epithelial integrity, neutrophil and macrophage function, cytokine regulation, and innate immune receptor signaling, resulting in asthma phenotypes that differ fundamentally from those seen in younger patients. In parallel, advances in biomarker research (including inflammatory mediators, cellular signatures, and epigenetic markers) offer new opportunities for improved phenotyping and precision management in elderly asthma. This mini-review synthesizes contemporary findings from reputable academic studies to summarize key innate immune alterations and candidate biomarkers relevant to asthma in older adults. By consolidating current evidence within a rapidly evolving field, this review aims to provide a clinically meaningful framework for researchers and clinicians seeking to better understand immune aging in asthma and to guide future investigation and targeted therapeutic strategies.
Introduction: The 8-item Inflammatory Bowel Disease control Questionnaire-8 (IBDcQ-8) is a patient-reported measure designed to capture the core domains of disease control and quality of life. The aim of this study was to evaluate the validity and reliability of the Persian version of the IBDcQ-8 in the Iranian IBD population. Methods: A standardized forward-backward translation procedure was employed to adapt the questionnaire into Persian. Content validity was evaluated through structured interviews with a panel of 10 evaluators. Construct validity was examined by structured interview and clinical visits of 101 patients. Harvey Bradshaw Index (HBI), partial Mayo score, and IBD Questionnaire (IBDQ) were used as comparator instruments. Patients' responses were compared with clinical global assessment, Harvey Bradshaw Index (HBI), partial Mayo score, IBDQ score , and laboratory markers using Spearman's rank correlation. Test-retest reliability was evaluated by calculating the intraclass correlation coefficient (ICC) between the two subsequent interviews. A P-value< 0.05 was considered statistically significant. Results: Half of the subjects (n = 51 (50.5%)) were female. The mean age was 38 years (SD = 14). Sixty-seven patients (66%) had UC. IBDcQ-8 scores showed strong correlations with HBI and IBDQ, and moderate correlations with the partial Mayo score, CRP, and clinical evaluation at the first visit (P-value < 0.05). Agreement was excellent for one-day follow-up (ICC = 0.82, 95% CI: 0.71-0.89, P < 0.001), and moderate for two-week follow-up (ICC = 0.61, 95% CI: 0.44-0.73, P< 0.001). Conclusion: The Persian version of the IBDcQ-8 questionnaire demonstrated robust validity and acceptable reliability even when administered by telephone interview, supporting its usefulness for evaluating disease-specific quality of life in patients with IBD and its applicability in future studies.
INTRODUCTION:Stroke remains a leading cause of death and disability worldwide, with high systolic blood pressure (HSBP) being a major modifiable risk factor. This study aimed to assess global trends, age- and SDI-specific patterns, and future projections of the stroke burden attributable to HSBP among adults aged≥45 years from 1990 to 2021. METHODS:Data were obtained from the Global Burden of Disease Study 2021. Mortality, disability-adjusted life years (DALYs), age-standardized mortality rate (ASMR), and age-standardized DALYs rate (ASDR) were analyzed across sex, age, and socio-demographic index (SDI) strata. Estimated annual percentage change (EAPC) was used to quantify temporal trends, and the ARIMA model was applied for projections to 2045. RESULTS:In 2021, global HSBP-attributable stroke deaths and DALYs among adults aged≥45 years reached 4.12 million and 86.18 million, respectively. From 1990 to 2021, the number of deaths increased by 51.5% and DALYs by 47.9%, despite declines in ASMR (EAPC=-1.72) and ASDR (EAPC=-1.61). Mortality and DALY rates increased with age in all SDI regions, peaking at 70-79 years, with low-SDI regions showing the highest rates and an earlier peak age. High-SDI regions recorded the lowest burden and largest declines in ASMR and ASDR. Projections indicate a continued global decline in mortality rates through 2045, with a faster reduction in females. CONCLUSION:Although the global age-standardized burden of HSBP-attributable stroke has declined, absolute cases continue to rise, especially among older adults and in low-SDI regions, highlighting the need for targeted prevention.
Background: Given the pivotal role of DNA methylation in the progression and severity of rheumatoid arthritis (RA), identifying a unique methylation pattern associated with the disease could support early detection, disease monitoring, and the development of personalized treatment plans. We aimed to explore the potential of OAS2 and OAS3 methylation levels in peripheral blood cells. These levels could be used to diagnose RA and predict patient outcomes. Methods: We collected 105 peripheral blood specimens from RA patients and 110 from healthy subjects. We then performed methylation analysis using the methylation-quantification of endonuclease-resistant DNA (MethyQESD) technique. Finally, we analyzed the data using appropriate nonparametric tests. Results: Our study revealed a significant decrease in OAS2 gene methylation in RA patients (P < 0.001). The ROC curve analysis further underscored the potential of OAS2 DNA methylation (AUC= 0.718, P < 0.001) to effectively distinguish RA patients from healthy individuals. Although OAS2 methylation was generally reduced in RA patients compared to controls, RA patients with a positive family history exhibited higher methylation than those without (P = 0.018). Moreover, increased OAS2 methylation was associated with reduced CRP levels (r =-0.317, P < 0.001). Conclusion: The methylation levels of OAS2 in peripheral blood cells show promise in distinguishing RA patients from healthy individuals. Furthermore, these levels show potential in identifying inflammation, a family history of RA, and other related disorders.
Background: In today's rapidly changing social and cultural landscape, recognizing the rights of Healthcare Professionals (HCPs) alongside those of the patients has become essential for a fair and sustainable healthcare system. While patient rights are widely acknowledged, HCPs in Iran often face heavy workloads, poor work-life balance, and reduced professional dignity. These challenges not only affect their well-being but can also compromise the quality of care the patients receive. This report presents the development of the "Charter of Rights for HCPs of Iran," prepared by the Supreme Council of the Iranian Medical Council (IMC). The charter aims to create a clear framework that protects HCPs' rights, promotes ethical practice, and supports the delivery of high-quality care nationwide. Development Process and Implementation: A comprehensive, consultative approach was used to develop the charter. The process began with a literature review, followed by semi-structured interviews with a diverse group of physicians, pharmacists, and dentists. Key themes were identified through content analysis, and the draft charter was refined based on feedback from focus groups and the Delphi method, ensuring its relevance, practicality, and acceptance by stakeholders. Key Findings: The charter includes six chapters and 59 articles addressing areas such as professional respect, workplace safety, fair compensation, continuing education, transparency, and professional autonomy. Each chapter outlines clear rights and responsibilities, highlighting the importance of balanced relationships between HCPs and patients. Discussion: The Iran HCPs' Charter of Rights presents a comprehensive framework for safeguarding healthcare professionals' rights, establishing multi-stakeholder accountability and addressing issues such as conscientious objection, aiming to mitigate systemic vulnerabilities and reduce dissatisfaction-driven turnover. This pioneering document offers a potential global model for balancing professional rights with quality patient care. Conclusion: Ratifying and implementing this charter represents a significant step toward recognizing and safeguarding the rights of HCPs in Iran. Its adoption is expected to enhance workforce well-being, strengthen ethical standards, and improve patient care. Future studies should assess the charter's impact and uptake by key national stakeholders to guide further improvements.
Background: Major depressive disorder (MDD), a major cause of the burden of diseases, is associated with a considerable rate of inadequate treatment and high costs. We assessed the pattern of service use, quality, and costs of healthcare for MDD in Iran. Methods: We assessed a national sample of 265 patients in the acute phase of MDD recruited from outpatient/inpatient settings at baseline and in three follow-up points of one, three, and six months. The pattern of service use and selected quality indicators were assessed, and the costs of care for an episode of MDD were estimated using the bottom-up approach. Results: The subjects were primarily female (73.6%), with a mean age of 43.3 years (±13.8). Of 173 respondents at the end of the study, 65.3% were on treatment for at least six months. Regarding quality indicators, the majority of the patients (97.7%) were prescribed antidepressants. However, only 71.2% of the patients initiated their antidepressants following prescription at the initial visit. At the end of the study, 40.1% were in remission and 58.1% had at least a 50% improvement in depressive symptoms. However, no standardized process or outcome measures were documented on the patients’ medical records. The average out-of-pocket and total costs for an episode of MDD per patient were estimated at Int$ 1331.4 and 2107.4, respectively. Conclusion: We recommend establishing an infrastructure for monitoring the clinical evaluation and treatment, and proper documentation based on standard quality of care, especially for ambulatory clinical practice.
Background: Liver disease is a leading cause of mortality among adults worldwide. Liver transplantation (LT) remains the only definitive treatment for patients with end-stage liver failure and has shown considerable success, particularly in high-volume centers in developing countries. Numerous factors can influence long-term survival following LT. This study aimed to identify the factors associated with survival among adult liver transplant recipients at Namazi Hospital, Shiraz between 2001 and 2018. Methods: This retrospective cohort study included 3712 adult patients who underwent liver transplantation for advanced liver failure. Demographic and clinical data were extracted from medical records. Cox regression models were used to assess factors associated with post-transplant survival. Data was analyzed using the SPSS and R software. Results: Of the 3712 patients, 742 (20%) died during follow-up. Also, 2348 (63.3%) patients were male, and the mean (SD) age was 42.3 (13.2) years (range: 19-74 years). In the multivariable Cox model, re-transplantation, older recipient and donor age, higher Model for End-Stage Liver Disease (MELD) score, and certain etiologies of liver disease were significantly associated with poorer survival. Conversely, transplantation performed in 2010 or later was independently associated with improved survival outcomes. Conclusion: Older recipient, donor age, and higher MELD score were independently associated with higher mortality after liver transplantation. Patients transplanted from 2010 onward experienced better survival, reflecting advancements in transplant care over time. Additionally, compared to acute liver failure (ALF), etiologies such as primary sclerosing cholangitis (PSC), autoimmune hepatitis (AIH), Budd-Chiari syndrome, cryptogenic liver disease, hepatitis B virus (HBV), and primary biliary cholangitis (PBC) were associated with significantly lower mortality risk and improved long-term survival.
Background: Cholangiocarcinoma (CCA) is the most common malignancy in patients with primary sclerosing cholangitis (PSC). It is typically associated with low survival rates due to late diagnosis. This study aimed to evaluate the predictors of incidental CCA in PSC patients. Methods: In this cross-sectional study, we included 425 patients aged 18 years or older who underwent liver transplant with a confirmed diagnosis of PSC. Demographic data, pre-transplant clinical features, and para-clinical evidence were obtained from medical records. Pathology experts examined livers removed during transplantation, and CCA was diagnosed accordingly. Multivariable logistic regression and receiver operating characteristic (ROC) curve analyses were conducted to assess the risk factors for incidental CCA and the effectiveness of carbohydrate antigen 19-9 (CA 19‒9) in predicting CCA, respectively. Results: Of the 425 included patients, 29 had PSC-CCA and 396 patients had PSC alone. According to the multivariable logistic model, CA 19‒9 (odds ratio [OR]=1.001, 95% confidence interval [CI]: 1.000‒1.001, P-value=0.041) and weight loss (OR=4.712, 95% CI: 1.392 to 15.947, P-value=0.013) were significantly associated with CCA development. ROC curve analysis also revealed that CA 19‒9 could predict CCA (AUC=0.737; 95% CI: 0.689‒0.782) at an optimal cut-off point above 46 U/mL, with a good sensitivity (68%, bootstrapped 95% CI: 62‒74%) and specificity (72.32%, bootstrapped 95% CI: 68‒76%). Conclusion: We found that CA 19‒9 and weight loss are independent predictors of incidental CCA in PSC patients, and a CA 19‒9 level above 46 U/mL has relatively good predictive power for incidental CCA.
Background: Obstructive jaundice commonly complicates pancreatic cancer and often requires biliary decompression. Percutaneous transhepatic biliary drainage (PTBD) followed by stent placement is used for palliation, but long-term stent patency and the relationship between patency and overall survival (OS) remain incompletely characterized. Methods: We conducted a retrospective cohort study of 60 consecutive patients who underwent sequential PTBD and biliary stent placement at the Affiliated Hospital of Jiangnan University (Wuxi, China) between January 2020 and December 2024. Primary endpoint was stent patency (time from stent insertion to radiologically confirmed occlusion or repeat intervention). Secondary endpoint was OS measured from stent insertion. Patient characteristics, stent type (covered vs uncovered), tumor location, stage, and receipt of systemic chemotherapy were extracted from electronic medical records. Kaplan-Meier analysis and Cox proportional hazards models (adjusted for age, sex, cancer stage, tumor location, baseline bilirubin and chemotherapy) were used. Proportional hazards assumption was tested using Schoenfeld residuals. Results: Median stent patency was 12.0 months (IQR 8.0-15.0) and median OS was 9.5 months (IQR 6.0-13.0). Covered stents were associated with longer patency (median 13.0 vs 11.0 months; log-rank P = 0.018). In multivariable Cox regression, Stage IV disease (adjusted HR 2.50; 95% CI 1.68-3.86; P < 0.001) and age (per year, adjusted HR 1.05; 95% CI 1.02-1.09; P= 0.002) were independent predictors of mortality; covered stent use was associated with lower mortality (adjusted HR 0.78; 95% CI 0.61-0.99; P = 0.043). Schoenfeld tests showed no violation of the proportional hazards assumption (global P= 0.18). Stent-related complications occurred in 16.7% of patients (migration 5.0%, infection 3.3%, biliary leak 1.7%, recurrent jaundice 6.7%). Conclusion: Sequential PTBD and biliary stenting provides effective biliary decompression with a median stent patency of 12 months but only limited impact on OS, which is dominated by disease stage. Covered stents improved patency and were associated with a modest survival advantage after adjustment. Prospective, multicenter studies are required to confirm these findings and to explore integration with systemic therapies.
Pancreatic perivascular epithelioid cell tumors (PEComas) are rare mesenchymal neoplasms with only a few reported cases. Their non-specific clinical presentations and imaging features often lead to misdiagnosis. We report a case of a 63-year-old female with intermittent left upper quadrant pain. Imaging revealed a hypervascular mass in the pancreatic tail, initially suspected to be a neuroendocrine tumor. The patient underwent distal pancreatectomy with splenectomy. Histopathological examination showed that the tumor consisted of epithelioid and spindle cells with clear cytoplasm, a rich vascular network and low mitotic activity. Immunohistochemically, the tumor cells were positive for HMB-45, Melan-A, and smooth muscle actin, confirming the diagnosis of pancreatic PEComa. The postoperative course was uneventful. Given the uncertain malignant potential of PEComas, complete surgical excision is the preferred treatment option, with long-term follow-up recommended. This case highlights the diagnostic challenges of pancreatic PEComas and underscores the role of histopathology and immunohistochemistry in their accurate identification and management.
Background: Thyroid cancer (TC) incidence varies regionally in Iran, with a notable increase observed in females. However, region-specific spatiotemporal epidemiological data are limited. This study aimed to quantify the spatiotemporal trends and geographic clustering of female TC in the Hamadan province, western Iran, from 2010 to 2019. Methods: Female TC cases from the Hamadan province were obtained from the population-based cancer registry. County-level standardized incidence ratios (SIRs) were calculated to adjust for differences in population size, and were smoothed using a hierarchical Bayesian spatial smoothing model that accounts for spatial and temporal dependence. Temporal trends were analyzed using joinpoint regression. Spatiotemporal clusters were identified using space-time scan statistics. Results: The incidence of female TC showed an average annual increase of 14.5% (Average annual percent change [AAPC]: 14.5, 95% confidence interval: 4.7 to 25.3; P < 0.001) from 2010 to 2019 in the Hamadan province. The smoothed SIRs indicated increasing trends in northern and central counties, including Hamadan, Asadabad, Famenin, Razan, and Tuyserkan, while decreasing trends were observed in southern counties such as Nahavand and Malayer. A significant high-risk spatiotemporal cluster was identified in the Hamadan county during 2018-2019 (observed-to-expected cases ratio: 2.24, P < 0.001), and a low-risk cluster was detected in Nahavand, Malayer, and Tuyserkan from 2010 to 2013 (0.51, P< 0.001). Conclusion: This study revealed significant spatiotemporal heterogeneity in female TC incidence in the Hamadan province. Identification of high-risk clusters provides an evidence base for targeted preventive measures and health resource allocation.
Background: Cervical cancer is the leading malignancy among women worldwide, posing clinical and public health challenges. This in silico study aims to identify potential diagnostic biomarkers, therapeutic targets, and prognostic markers associated with cervical cancer through integrative bioinformatics approaches. Methods: A hybrid machine learning approach, combining genetic algorithm (GA) and support vector machine (SVM), was applied to high-dimensional gene expression data from publicly available transcriptomic datasets, including the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). A total of 72 Geo samples (Affymetrix, Illumina) served as the primary dataset after normalization. Results: The GA-SVM model achieved about 99% accuracy and AUC with 10-fold cross validation, clearly separating cervical cancer from normal tissues. Eight genes (CXCL9, CTGF, ZNF704, ZEB2, SASH1, PTN, KPNA2, SLC5A1) were identified as diagnostic biomarkers. Protein-protein interaction (PPI) and functional enrichment analyses revealed 42 therapeutic targets (e.g. CDK1, BRCA1, CCNB1, and AURKB) linked to regulating cell cycle, DNA repair, and mitotic processes. Survival analysis identified six genes (CXCL1, DNMT1, MMP1, MYBL2, PCNA, and RRM2) as key prognostic markers. Additionally, transcription factor analysis identified E2F1 and TP63 as major regulators of the prognostic genes, elucidating the molecular mechanisms underlying cervical cancer progression. Conclusion: The identified gene signatures may serve as candidates for hypothesis generation and provide a computational framework to prioritize biomarkers and therapeutic targets in cervical cancer. However, these findings are based on in silico analyses and require experimental and clinical validation before translation into practice.
