KMT2D links TGF-ß signaling to noncanonical activin pathway and regulates pancreatic cancer cell plasticity.

Although KMT2D, also known as MLL2, is known to play an essential role in development, differentiation, and tumor suppression, its role in pancreatic cancer development is not well understood. Here, we discovered a novel signaling axis mediated by KMT2D, which links TGF-ß to the activin A pathway. We found that TGF-ß upregulates a microRNA, miR-147b, which in turn leads to post-transcriptional silencing of KMT2D. Loss of KMT2D induces the expression and secretion of activin A, which activates a noncanonical p38 MAPK-mediated pathway to modulate cancer cell plasticity, promote a mesenchymal phenotype, and enhance tumor invasion and metastasis in mice. We observed a decreased KMT2D expression in human primary and metastatic pancreatic cancer. Furthermore, inhibition or knockdown of activin A reversed the protumoral role of KMT2D loss. These findings support a tumor-suppressive role of KMT2D in pancreatic cancer and identify miR-147b and activin A as novel therapeutic targets.

A global study of the association of cesarean rate and the role of socioeconomic status in neonatal mortality rate in the current century.

INTRODUCTION: Caesarean section (C/S) rates have significantly increased across the world over the past decades. In the present population-based study, we sought to evaluate the association between C/S and neonatal mortality rates. MATERIAL AND METHODS: This retrospective ecological study included longitudinal data of 166 countries from 2000 to 2015. We evaluated the association between C/S rates and neonatal mortality rate (NMR), adjusting for total fertility rate, human development index (HDI), gross domestic product (GDP) percentage, and maternal age at first childbearing. The examinations were also performed considering different geographical regions as well as regions with different income levels. RESULTS: The C/S rate and NMR in the 166 included countries were 19.97% ± 10.56% and 10 ± 10.27 per 1000 live birth, respectively. After adjustment for confounding variables, C/S rate and NMR were found correlated (r = -1.1, p < 0.001). Examination of the relationship between C/S rate and NMR in each WHO region resulted in an inverse correlation in Africa (r = -0.75, p = 0.005), Europe (r = -0.12, p < 0.001), South-East Asia (r = -0.41, p = 0.01), and Western Pacific (r = -0.13, p = 0.02), a direct correlation in America (r = 0.06, p = 0.04), and no correlation in Eastern Mediterranean (r = 0.01, p = 0.88). Meanwhile, C/S rate and NMR were inversely associated in regions with upper-middle (r = -0.15, p < 0.001) and lower-middle (r = -0.24, p < 0.001) income levels, directly associated in high-income regions (r = 0.02, p = 0.001), and not associated in low-income regions (p = 0.13). In countries with HDI below the centralized value of 1 (the real value of 0.9), the correlation between C/S rate and NMR was negative while it was found positive in countries with HDI higher than the mentioned cut-off. CONCLUSIONS: This study indicated that NMR associated with C/S is dependent on various socioeconomic factors such as total fertility rate, HDI, GDP percentage, and maternal age at first childbearing. Further attentions to the socioeconomic status are warranted to minimize the NMR by modifying the C/S rate to the optimum cut-off.

Resveratrol as an antitumor agent for glioblastoma multiforme: Targeting resistance and promoting apoptotic cell deaths.

Glioblastoma multiforme (GBM) is one of the most aggressive brain and spinal cord tumors. Despite the significant development in application of antitumor drugs, no significant increases have been observed in the survival rates of patients with GBM, as GBM cells acquire resistance to conventional anticancer therapeutic agents. Multiple studies have revealed that PI3K/Akt, MAPK, Nanog, STAT 3, and Wnt signaling pathways are involved in GBM progression and invasion. Besides, biological processes such as anti-apoptosis, autophagy, angiogenesis, and stemness promote GBM malignancy. Resveratrol (RESV) is a non-flavonoid polyphenol with high antitumor activity, the potential of which, regulating signaling pathways involved in cancer malignancy, have been demonstrated by many studies. Herein, we present the potential of RESV in both single and combination therapy- targeting various signaling pathways- which induce apoptotic cell death, re-sensitize cancer cells to radiotherapy, and induce chemo-sensitizing effects to eventually inhibit GBM progression.

Corrigendum: Updates in the Diagnosis of Intraductal Neoplasms of the Pancreas.

[This corrects the article DOI: 10.3389/fphys.2022.856803.].

Updates in the Diagnosis of Intraductal Neoplasms of the Pancreas.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest types of cancer worldwide. There are many reasons for this dismal prognosis, including the advanced stage at the time of diagnosis and the lack of effective therapeutic approaches. Intraductal papillary mucinous neoplasms (IPMNs) represent detectable and treatable precursor lesions of PDAC. Our understanding of the pathology of IPMNs has evolved over the past few decades, and new advances in diagnostic tools have emerged. The new World Health Organization (WHO) classification scheme now recognizes the previously considered variants of IPMNs, such as intraductal oncocytic papillary neoplasms (IOPNs) and intraductal tubulopapillary neoplasms (ITPNs), as distinct neoplasms. New imaging and molecular diagnostic tests are being developed to recognize these PDAC precursor lesions better. Here, we review the advances in diagnostic tools for IPMNs, IOPNs, and ITPNs, emphasizing the new (5th edition, 2019) WHO classification for pathological diagnosis, molecular markers, new laboratory tests, and imaging tools.

Intravenous morphine plus ibuprofen or ketorolac versus intravenous morphine alone in reducing renal colic pain intensity in emergency department: A randomized, double-blind clinical trial.

OBJECTIVES: This study aimed to compare the efficacy of intravenous (IV) morphine plus ibuprofen or ketorolac versus IV morphine alone in controlling renal colic pain in the emergency department. METHODS: This double-blind, randomized clinical trial was conducted during November 2018 and March 2019 in Iran. Patients aged 18-65 years with acute renal colic and numerical rating scale (NRS) score of higher than 6 of 10 were enrolled to the study. They were randomly assigned to I, K, and control groups receiving 5 mg morphine with 800 mg ibuprofen (n = 65), 5 mg morphine with 30 mg ketorolac (n = 65), or only 5 mg morphine (n = 65) intravenously, respectively. NRS was evaluated 0, 15, 30, 60, and 120 min after injection. RESULTS: A total of 195 participants took part in the study. The presence of stone in pelvis area was higher in I group (P = 0.027). The mean rescue analgesic dose was higher in the control group and lower in K group (P = 0.031). From the 15th min, the NRS reduction in I and K group was higher than the control group (P < 0.001), but the difference between I and K group was not statistically significant in total (P = 1.0) or in the all follow-up time intervals (15th P = 0.864, 30th P = 0.493, 60th P = 0.493, and 120th min P = 1.0). The largest difference in pain reduction was observed in 120th min and mean of NRS was 2.9 (95% confidence interval [CI]: 2.6-3.3), 2.9 (95% CI: 2.6-3.3) and 7.0 (95% CI: 6.7-7.4) in I, K and control group, respectively. The adverse effects showed in 18.5%, 20.0%, and 13.8% of I, K, and control group, respectively. CONCLUSION: IV ibuprofen plus morphine and IV ketorolac plus morphine had similar effects in reducing renal colic pain but were more effective than IV morphine alone.

Computational Analysis of Gly482Ser Single-Nucleotide Polymorphism in PPARGC1A Gene Associated with CAD, NAFLD, T2DM, Obesity, Hypertension, and Metabolic Diseases.

Peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PPARGC1A) regulates the expression of energy metabolism's genes and mitochondrial biogenesis. The essential roles of PPARGC1A encouraged the researchers to assess the relation between metabolism-related diseases and its variants. To study Gly482Ser (+1564G/A) single-nucleotide polymorphism (SNP) after PPARGC1A modeling, we substitute Gly482 for Ser482. Stability prediction tools showed that this substitution decreases the stability of PPARGC1A or has a destabilizing effect on this protein. We then utilized molecular dynamics simulation of both the Gly482Ser variant and wild type of the PPARGC1A protein to analyze the structural changes and to reveal the conformational flexibility of the PPARGC1A protein. We observed loss flexibility in the RMSD plot of the Gly482Ser variant, which was further supported by a decrease in the SASA value in the Gly482Ser variant structure of PPARGC1A and an increase of H-bond with the increase of ß-sheet and coil and decrease of turn in the DSSP plot of the Gly482Ser variant. Such alterations may significantly impact the structural conformation of the PPARGC1A protein, and it might also affect its function. It showed that the Gly482Ser variant affects the PPARGC1A structure and makes the backbone less flexible to move. In general, molecular dynamics simulation (MDS) showed more flexibility in the native PPARGC1A structure. Essential dynamics (ED) also revealed that the range of eigenvectors in the conformational space has lower extension of motion in the Gly482Ser variant compared with WT. The Gly482Ser variant also disrupts PPARGC1A interaction. Due to this single-nucleotide polymorphism in PPARGC1A, it became more rigid and might disarray the structural conformation and catalytic function of the protein and might also induce type 2 diabetes mellitus (T2DM), coronary artery disease (CAD), and nonalcoholic fatty liver disease (NAFLD). The results obtained from this study will assist wet lab research in expanding potent treatment on T2DM.

Distress and depression among patients with diabetes mellitus: prevalence and associated factors: a cross-sectional study.

PURPOSE: This study aimed to validate the internal consistency of the Persian version of the diabetes distress scale-17 (DDS-17) and to investigate the prevalence of diabetes distress (DD), depression, and possible relevant factors. METHODS: This was a cross-sectional study on 820 diabetes patients (62.4 % females) in Tehran, Iran between January and June 2017. The Ethics Committee of Shahid Beheshti University of Medical Sciences approved the protocol. Patients filled out a demographic and health survey, DDS-17, the Beck Depression Inventory Second Edition (BDI-II) and the Summary of Diabetes Self-Care Activities Measure (SDSCA). DDS-17 consist of emotional burden, and physician, regimen, and interpersonal related distress. The correlation between DDS subscales and association between DDS and BDI-II or SDSCA scores were assessed using SPSS. RESULTS: The mean age was 58.91 ± 12.35 years. Majority of patients had high DD (37.2 %) and severe depression (38.7 %). The general and specific diets got the highest score in six SDSCA subscales. The Persian version of DDS-17 had excellent internal consistency with Cronbach's alpha coefficient of 0.924. The DDS score had significant relationship with socioeconomic level (p < .001), type of DM (p < .001), type of treatment (p < .001), glycemic control status (p < .001), complication (p < .001) and depression level (p < .001). The level of hemoglobin A1c was the most useful predictor of DDS score (p < .001). CONCLUSIONS: High prevalence of depression and distress in patient with diabetes calls for greater emphasizes on the importance of enhanced physicians and patients' knowledge in these areas.

Association study between superoxide Dismutases gene polymorphisms and development of diabetic retinopathy and cataract in Iranian patients with type two diabetes mellitus.

PURPOSE: Reactive oxygen species (ROS) plays pathological roles on development of diabetic retinopathy (DR) and cataract. Superoxide dismutases (SODs) are a set of enzymes to eliminate ROS and cell protection. Based on the diminished activities of SOD1 during DR and cataract, the polymorphisms within SOD1 gene may be associated with these disorders. This study assessed the relationship between SOD1 -251A/G (rs2070424) and SOD1 + 35A/C (rs2234694) gene polymorphisms and DR and cataract in Iranian patients with type 2 diabetes mellitus (T2DM). METHODS: Totally, 141 cases (73 patients with cataract and 68 with DR) with a at least five years history of T2DM and 119 age/gender matched persons without history of DM were included in the case and control groups, respectively. Genomic DNA was extracted from peripheral venous blood cells and genotyping of 251A/G and + 35A/C polymorphisms was done using PCR-RFLP technique. Statistical analysis was done using SPSS version 22. RESULTS: Results showed SOD1 -251A/G and + 35A/C genotype frequency were significantly associated (1.9 folds) with cataract (P = 0.045, OR = 0.524, 95% CI = 0.277-0.991 and P = 0.037, OR = 0.505, 95% CI = 0.265-.0965, respectively). Instead, no significant differences found between SOD -251A/G (P = 0.053, OR = 0.52, 95% CI = 0.276-1.014) and + 35A/C (P = 0.073, OR = 0.547, 95% CI = 0.281-1.063) polymorphisms and DR. Multivariate Logistic Regression model showed significant relationship between BMI, HDL and TC levels and independent predictors of T2DM (P < 0.05). CONCLUSIONS: Based on the results, there was significant association between SOD1 gene polymorphisms and cataract in patients with T2DM. Therefore, SOD1 gene polymorphisms might be a potential marker for increased risk of cataract in patients with T2DM.

Can fasting plasma glucose replace oral glucose-tolerance test for diagnosis of gestational diabetes mellitus?

BACKGROUND AND AIMS: Gestational diabetes mellitus (GDM) has high prevalence worldwide. This study aimed to evaluate the fasting plasma glucose (FPG) cutoffs at first prenatal visit and at 24-28th of gestational weeks to avoid obtaining full oral glucose-tolerance test (OGTT) in the diagnosis of GDM. METHODS: This study was a cross-sectional study conducted in Tehran, Iran during October 2016 and November 2017. All pregnant women reporting for the first routine prenatal visit before 20th week of gestational age were included in this study. Participants without overt diabetes mellitus at first prenatal visit, underwent OGTT at 24-28th of gestational weeks. RESULTS: Totally 952 pregnant women with mean age of 26.4 ± 14.1 years took part in this study. The prevalence of GDM was 12.7% (mostly diagnosed based on the FPG alone). FPG cutoffs 75 and 80 mg/dL at first prenatal visit and at 24-28th of gestational weeks can rule out the GDM with high sensitivity and negative predictive value, respectively. FPG cutoffs 85 and 90 mg/dL at first prenatal visit and at 24-28th of gestational weeks had high capacity, excellent specificity and positive predictive value in diagnosing GDM, respectively. CONCLUSIONS: Performing only the FPG and considering FPG cutoffs 75 and 80 mg/dL at first prenatal visit and at 24-28th of gestational weeks can be a useful tool predicting the incidence of GDM, respectively, and had similar diagnostic power.

The Possible Factors Correlated with The Higher Risk of Getting Infected by COVID-19 in Emergency Medical Technicians; A Case-Control Study.

OBJECTIVE: To assess the possible factors associated with increasing risk of COVID-19 among EMTs. METHODS: This study was a case-control study conducted in Tehran, Iran. Case group was consisted of confirmed COVID-19 EMTs based on the results of reverse transcriptase polymerase chain reaction and/or lung computed tomography scan. Healthy EMTs were randomly selected as control group. Patients were asked to fill out a checklist including demographic data, data related to the work situation (such as number of missions and type of mask and cloth) and PPE precautions. RESULTS: Sixty-eight patients and 148 healthy persons took part in this study as case and control group, respectively. Having two EMTs involved directly in taking care of patients (p<0.001) and working with a confirmed case teammate (p<0.001), considering the precautions such as seal check after wearing the mask (p=0.015), covering the hair with a medical hat (p<0.001), not using personal items despite protective clothing (p<0.001), and avoiding contact with the outer surface of clothing while removing (p<0.001) had significant difference in two groups. CONCLUSION: We found that the type and method of use of PPE were correlated with the increasing risk of COVID-19 in EMTs. Also, we found that when two EMTs were involved directly in taking care of the patients, and those who worked with a confirmed case teammate, more frequently affected.

Merkel cell carcinoma on the right calf in association with chronic lymphocytic leukemia: A case report.

This study showed a rare case of Merkel cell carcinoma (MCC) with atypical manifestations accompanied by chronic lymphocytic leukemia of B-cell type that underwent chemotherapy and had poor prognosis. The findings suggest that the physicians should consider MCC when performing diagnosis and assess all possible associated risk factors like neoplasms to achieve good prognosis.

Antibody Rapid Test Results in Emergency Medical Services Personnel during COVID-19 Pandemic; a Cross Sectional study.

INTRODUCTION: Like other infectious diseases, it is expected that COVID-19 will mostly end with the development of neutralizing antibody immunity. This study aimed to evaluate the value of COVID-19 antibody rapid test assessment in emergency medical services (EMS) personnel. METHODS: This cross-sectional study was conducted in Tehran, Iran from 20th March until 20th May 2020. The results of chest computed tomography (CT) scan, and antibody rapid test were compared in EMS personnel with confirmed COVID-19, as well as symptomatic and asymptomatic ones who had exposure to a probable/confirmed COVID-19 teammate. In symptomatic or asymptomatic individuals who were only IgM-positive, chest CT scan or RT-PCR was recommended. RESULTS: A total of 243 EMS personnel with the mean age of 36.14±8.70 (range 21 to 59) years took part in this study (87.7% were males). Most of the participants (73.3%) had history of exposure. One hundred sixty-three EMS personnel were tested using either RT-PCR test or chest CT-scan or both, and 78 (47.9%) of them had at least one positive result. Among the participants who had undergone chest CT-scan and/or RT-PCR test (n=163), 78 had positive chest CT-scan and/or RT-PCR test; of these, 18 individuals had negative results for IgM and IgG. The rate of positive IgM and IgG in participants with positive chest CT-scan was 1.6 or 1.3 times more than those with negative chest CT-scan, respectively (p < 0.05). The percentage of positive results for both IgM and IgG in participants having positive RT-PCR test was 1.7 times more than those having negative RT-PCR test (p < 0.05). CONCLUSION: Rapid antibody test could help in diagnosis of COVID-19 in asymptomatic or symptomatic EMS personnel who did not undergo RT-PCR test or the test was reported as negative. However, its sensitivity could be enhanced through use along with other diagnostic methods.

A Rare Case of Simultaneous Intrahepatic and Porcelain Gallbladder: Case Report.

Intrahepatic gallbladder is a rare anomaly that is due to the failure of gallbladder migration from liver to its proper position. This condition increases the risk of cholelithiasis, hepatic abscess and cholangiocarcinoma. Calcification in the wall of the gallbladder, which is known as porcelain gallbladder, also increases the risk of malignancy. In this report a 47-year-old man presented at the emergency department with continuous right upper quadrant abdominal pain who was misdiagnosed with acute cholecystitis. During abdominal surgery, gallbladder was not detectable in its proper location. Therefore, the patient underwent enhanced abdominal computed tomography scan and magnetic resonance cholangiopancreatography and the results showed an intrahepatic porcelain gallbladder. In order to avoid future complications, intrahepatic gallbladder should always be considered in patients whose physical examination and radiologic findings do not match.

Glycemic control and associated factors among Iranian population with type 2 diabetes mellitus: a cross-sectional study.

PURPOSE: Detection and modification of various factors such as life style, smoking and so on can significantly improve the glycemic control status. This study aimed to investigate glycemic control status and its relevant factors among patients with Type 2 DM. METHODS: In this cross-sectional study, the glycemic control status of patients with type 2 DM was investigated. In addition, relevant risk factors including demographic, clinical characteristics, self-care management behavior, medication adherence and laboratory data and their relationship with glycemic control status were assessed. Glycemic control status was defined as very good (HbA1c < 7%), good (HbA1c = 7-7.9%), poor (HbA1c = 8-9.9%) or extremely bad (HbA1c ≥ 10%). RESULTS: The present study included 562 patients (64.4% female). Most of the patients (37%) had poor glycemic control status. Microvascular complications especially diabetic neuropathy were the most common complications in our study. Glycemic control had significant relationship with level of education (p < .01) and occupation (p = .04). Among laboratory parameters, fasting plasma glucose (FPG) and total cholesterol levels were significantly lower in patients with desirable glycemic control (p < .05). The linear regression test showed that HbA1c had significant relationship with FPG (p < .01) and increasing one standard deviation in FPG can increase the level of HbA1c 0.014. CONCLUSION: Glycemic control status in our study was very low and FPG was the strongest predictor of glycemic control status. Some other factors were also associated such as education level, occupation, type of treatment, diastolic blood pressure, the lipid profile and aspartate transaminase.

The Relation between Atherosclerosis Plaque Composition and Plaque Rupture.

BACKGROUND: Intima, media, and adventitia are three layers of arteries. They have different structures and different mechanical properties. Damage to intima layer of arteries leads to an inflammatory response, which is usually the reason for atherosclerosis plaque formation. Atherosclerosis plaques mainly consist of smooth muscle cells and calcium. However, plaque geometry and mechanical properties change during time. Blood flow is the source of biomechanical stress to the plaques. Maximum stress that atherosclerosis plaque can burden before its rupture depends on fibrous cap thickness, lipid core, calcification, and artery stenosis. When atherosclerotic plaque ruptures, the blood would be in contact with coagulation factors. That is why plaque rupture is one of the main causes of fatality. METHOD: In this article, the coronary artery was modeled by ANSYS. First, fibrous cap thickness was increased from 40 µm to 250 µm by keeping other parameters constant. Then, the lipid pool percentage was incremented from 10% to 90% by keeping other parameters unchanged. Furthermore, for investigating the influence of calcium in plaque vulnerability, calcium was modeled in both agglomerated and microcalcium form. RESULTS: It is proved that atherosclerosis plaque stress decreases exponentially as cap thickness increases. Larger lipid pool leads to more vulnerable plaques. In addition, the analysis showed maximum plaque stress usually increases in calcified plaque as compared with noncalcified plaque. CONCLUSION: The plaque stress is dependent on whether calcium is agglomerated near the lumen or far from it. However, in both cases, the deposition of more calcium in calcified plaque reduces maximum plaque stress.

The prevalence of autoimmune diseases in patients with multiple sclerosis: A cross-sectional study in Qom, Iran, in 2018.

Background: Multiple sclerosis (MS) is one of the most common autoimmune diseases worldwide and various autoimmune comorbidities are reported with MS. The objective of this study is to estimate the prevalence of the autoimmune diseases' comorbidity in patients with MS. Methods: In this cross-sectional study, we investigated a group of patients with MS in terms of age, gender, duration of MS, presence of simultaneous autoimmune diseases, such as Graves' disease, Hashimoto's thyroiditis, type 1 diabetes mellitus (DM), and systemic lupus erythematous (SLE). Results: This study included 1215 patients with MS, of which 70.8% were women. The mean age of participants was 33.70 ± 27.63 years. 55 patients (4.5%) had at least one autoimmune disease. The most common comorbidity was for Hashimoto's thyroiditis (30 patients). The frequency of simultaneous autoimmune disease was higher in women. Mean age (P = 0.01), mean duration of MS (P = 0.03), and mean age on MS diagnosis (P = 0.02) were significantly higher in simultaneous MS and other autoimmune diseases. Conclusion: Our study revealed that the probability of autoimmune diseases co-occurrence in patients with MS could be higher in older patients, in longer duration of disease, and also in patients with higher age at time of MS diagnosis.

Point-of-care ultrasound modalities in terms of diagnosing acute decompensated heart failure in emergency department; a diagnostic accuracy study.

This study aimed to compare the diagnostic accuracy of heart, lung and inferior vena cava (IVC) ultrasonography modalities, alone and combined, for possible added accuracy in diagnosing acute decompensated heart failure (ADHF), in a group of patients with the final diagnosis of ADHF based on plasma level of B-type natriuretic peptide (BNP) as the standard. The present study is a diagnostic accuracy study, which was carried out in the emergency department of Imam Khomeini hospital, affiliated to Tehran University of Medical Sciences, in 2014-2015. All patients over 18 years old, who were referred to emergency department with complaint of acute dyspnea were regarded as eligible and no exclusion criteria were considered. All ultrasounds were performed by a trained emergency medicine resident and then saved and classified for each patient, separately, and reviewed by the attending emergency medicine physician. In this study, patients with BNP levels higher than 500 pg/ml were considered positive for dyspnea caused by heart failure. A total of 120 patients with an average age of 60.83 ± 16.528 years were studied, 64 (53%) of which were male. In total, 47.5% of patients had a BNP level over 500 pg/ml. Among patients with positive ultrasound, 94.7% were true positive and among those with a negative ultrasound, 61.4% were true negative. Based on the findings, B-line ≥ 10 has the highest specificity and left ventricular ejection fraction (LVEF) < 45% has the highest sensitivity. The combination of LVEF and IVC collapsibility index (IVC-CI), LVEF and BLC, IVC-CI and BLC, and IVC-CI and BBPC had a higher specificity rate and combination of LVEF and BBPC and BLC and BBPC had the highest sensitivity. Sensitivity, specificity, positive predictive value and negative predictive value of all three ultrasounds combined were 31.6%, 98.4%, 94.7% and 61.4%, respectively. In this study, the diagnostic accuracy of double and triple ultrasonography of heart, lung and IVC in the diagnosis of ADHF was very high, among which triple ultrasonography was more preferable.

A clinical prediction rule for uncomplicated ureteral stone: The STONE score; a prospective observational validation cohort study.

INTRODUCTION: Renal colic is one of the most common complaints in patients admitted to Emergency Department (ED). Computed Tomography (CT) is the reference standard for the diagnosis of any stones in the kidneys or ureters. However, CT has classical disadvantages, such as radiation exposure, cost and availability. Recently, STONE clinical prediction criteria were suggested to identify uncomplicated ureteral stone cases among patiens admitted to the ED with abdominal pain. Primary objective of this study was the external validation of the STONE criteria. METHODS: This was a diagnostic accuracy study conducted on a prospective, observational cohort. All consecutive patients who underwent a non-enhanced abdominopelvic CT scan in the ED with an initial diagnosis of ureteral stone disease were enrolled. Using a pre-prepared checklist, all data and the final diagnosis according to the CT scan were recorded. STONE score was calculated for all patients. The area under the curve (AUC) of the STONE Score and the CT, the reference standard, were compared using the ROC curve analysis. RESULTS: Totally, 237 patients (59.9% male) with an average age of 41.54 years (SD: 13.37) were evaluated, and 156 cases (65.8%) were proved to have renal stone. The mean (SD) STONE scores in the groups of patients with renal stone and in the group of patients without renal stone group were 9.1 (2.6) and 6.0 ( 2.8), respectively (p < 0.001). The area under the curve (AUC) for the STONE score was 0.789 (95% confidence interval (CI) 0.725 to 0.852). The optimum threshold value of the STONE score for the diagnosis of a renal stone was 8 or more, which had a sensitivity of 75.0% and a specificity of 70.4%. CONCLUSION: Despite the acceptable diagnostic accuracy, further modifications and enhancements of the STONE score are needed to differentiate patients with low risk prior to imaging.