A pilot study of volumetric and density tumor analysis of ACC patients treated with vorinostat in a phase II clinical trial.

Rationale and objectives: Adenoid cystic carcinoma (ACC) is a rare salivary gland cancer. The vast majority of clinical trials evaluating systemic therapy efficacy in solid tumors use the Response Evaluation Criteria in Solid Tumors (RECIST) to measure response that is limited to 2 dimensional only evaluations, not taking volume or density into account. The indolent behavior ACC represents a challenge toward an appropriate evaluation of therapy response. Objectives: 1) To describe and contrast volumetric and density changes at each time-point, including changes noted from baseline to best response, to currently used 2 dimensional-only criteria (RECIST) and 2) To report the coefficient of variation in volume measurement among three reviewers on a subset of ACC patients. Materials and methods: We retrospectively assessed a cohort of 18 prospectively treated patients with ACC in a phase 2 trial with vorinostat using a volumetric (viable tumor volume, VTV) and density criteria. Three independent and blinded observers segmented target lesions across a sample of randomly selected computed tomography (CT) exams to examine inter-observer variation. Results: We found that the average coefficient of variation among observers for all target lesions was 16.1%, with lung lesions displaying a smaller variation at 14.0% (p-value >0.17). We describe examples of decrease in volume and density in several lesions despite stable disease by RECIST. Conclusion: This pilot study demonstrates that two-dimensional criteria such as RECIST may not be the best criteria to assess response to therapy, especially with evolving tools within picture archiving and communication system (PACS) that can assess volumetric size, density and texture, however, this should be prospectively studied.

Randomized, Double-Blind, Placebo-Controlled Phase II Study of Yeast-Brachyury Vaccine (GI-6301) in Combination with Standard-of-Care Radiotherapy in Locally Advanced, Unresectable Chordoma.

BACKGROUND: Brachyury is a transcription factor overexpressed in chordoma and is associated with chemotherapy resistance and epithelial-to-mesenchymal transition. GI-6301 is a recombinant, heat-killed Saccharomyces cerevisiae yeast-based vaccine targeting brachyury. A previous phase I trial of GI-6301 demonstrated a signal of clinical activity in chordomas. This trial evaluated synergistic effects of GI-6301 vaccine plus radiation. MATERIALS AND METHODS: Adults with locally advanced, unresectable chordoma were treated on a randomized, placebo-controlled trial. Patients received three doses of GI-6301 (80 × 107 yeast cells) or placebo followed by radiation, followed by continued vaccine or placebo until progression. Primary endpoint was overall response rate, defined as a complete response (CR) or partial response (PR) in the irradiated tumor site at 24 months. Immune assays were conducted to evaluate immunogenicity. RESULTS: Between May 2015 and September 2019, 24 patients enrolled on the first randomized phase II study in chordoma. There was one PR in each arm; no CRs were observed. Median progressive-free survival for vaccine and placebo arms was 20.6 months (95% confidence interval [CI], 5.7-37.5 months) and 25.9 months (95% CI, 9.2-30.8 months), respectively. Hazard ratio was 1.02 (95% CI, 0.38-2.71). Vaccine was well tolerated with no vaccine-related serious adverse events. Preexisting brachyury-specific T cells were detected in most patients in both arms. Most patients developed T-cell responses during therapy, with no difference between arms in frequency or magnitude of response. CONCLUSION: No difference in overall response rate was observed, leading to early discontinuation of this trial due to low conditional power to detect statistical difference at the planned end of accrual. IMPLICATIONS FOR PRACTICE: Chordoma is a rare neoplasm lacking effective systemic therapies for advanced, unresectable disease. Lack of clinically actionable somatic mutations in chordoma makes development of targeted therapy quite challenging. While the combination of yeast-brachyury vaccine (GI-6301) and standard radiation therapy did not demonstrate synergistic antitumor effects, brachyury still remains a good target for developmental therapeutics in chordoma. Patients and their oncologists should consider early referral to centers with expertise in chordoma (or sarcoma) and encourage participation in clinical trials.

TCR-engineered T cells targeting E7 for patients with metastatic HPV-associated epithelial cancers.

Genetically engineered T cell therapy can induce remarkable tumor responses in hematologic malignancies. However, it is not known if this type of therapy can be applied effectively to epithelial cancers, which account for 80-90% of human malignancies. We have conducted a first-in-human, phase 1 clinical trial of T cells engineered with a T cell receptor targeting HPV-16 E7 for the treatment of metastatic human papilloma virus-associated epithelial cancers (NCT02858310). The primary endpoint was maximum tolerated dose. Cell dose was not limited by toxicity with a maximum dose of 1 × 1011 engineered T cells administered. Tumor responses following treatment were evaluated using RECIST (Response Evaluation Criteria in Solid Tumors) guidelines. Robust tumor regression was observed with objective clinical responses in 6 of 12 patients, including 4 of 8 patients with anti-PD-1 refractory disease. Responses included extensive regression of bulky tumors and complete regression of most tumors in some patients. Genomic studies, which included intra-patient tumors with dichotomous treatment responses, revealed resistance mechanisms from defects in critical components of the antigen presentation and interferon response pathways. These findings demonstrate that engineered T cells can mediate regression of common carcinomas, and they reveal immune editing as a constraint on the curative potential of cellular therapy and possibly other immunotherapies in advanced epithelial cancer.

Phase I Study of Cabozantinib and Nivolumab Alone or With Ipilimumab for Advanced or Metastatic Urothelial Carcinoma and Other Genitourinary Tumors.

PURPOSE: We assessed the safety and efficacy of cabozantinib and nivolumab (CaboNivo) and CaboNivo plus ipilimumab (CaboNivoIpi) in patients with metastatic urothelial carcinoma (mUC) and other genitourinary (GU) malignances. PATIENTS AND METHODS: Patients received escalating doses of CaboNivo or CaboNivoIpi. The primary objective was to establish a recommended phase II dose (RP2D). Secondary objectives included objective response rate (ORR), progression-free survival (PFS), duration of response (DoR), and overall survival (OS). RESULTS: Fifty-four patients were enrolled at eight dose levels with a median follow-up time of 44.6 months; data cutoff was January 20, 2020. Grade 3 or 4 treatment-related adverse events (AEs) occurred in 75% and 87% of patients treated with CaboNivo and CaboNivoIpi, respectively, and included fatigue (17% and 10%, respectively), diarrhea (4% and 7%, respectively), and hypertension (21% and 10%, respectively); grade 3 or 4 immune-related AEs included hepatitis (0% and 13%, respectively) and colitis (0% and 7%, respectively). The RP2D was cabozantinib 40 mg/d plus nivolumab 3 mg/kg for CaboNivo and cabozantinib 40 mg/d, nivolumab 3 mg/kg, and ipilimumab 1 mg/kg for CaboNivoIpi. ORR was 30.6% (95% CI, 20.0% to 47.5%) for all patients and 38.5% (95% CI, 13.9% to 68.4%) for patients with mUC. Median DoR was 21.0 months (95% CI, 5.4 to 24.1 months) for all patients and not reached for patients with mUC. Median PFS was 5.1 months (95% CI, 3.5 to 6.9 months) for all patients and 12.8 months (95% CI, 1.8 to 24.1 months) for patients with mUC. Median OS was 12.6 months (95% CI, 6.9 to 18.8 months) for all patients and 25.4 months (95% CI, 5.7 to 41.6 months) for patients with mUC. CONCLUSION: CaboNivo and CaboNivoIpi demonstrated manageable toxicities with durable responses and encouraging survival in patients with mUC and other GU tumors. Multiple phase II and III trials are ongoing for these combinations.

Adherence to the algorithmic approach for diagnosis of pulmonary embolism: A teaching hospital experience, Shiraz, Iran.

BACKGROUND: We evaluated to see if the algorithmic approach of pulmonary embolism (PE) [Wells' score, followed by D-dimer test and computed tomography pulmonary angiography (CTPA)] is appropriately followed in teaching hospitals of Shiraz, Iran. METHODS: From October 2012 to October 2013, we prospectively calculated Wells' score for all patients who underwent CTPA with clinical suspicion to PE; patients with low probability who had not checked the D-dimer or had low level of D-dimer were considered as non-adherent to the guideline and those with high level of D-dimer or high probability of Wells' score were labeled as adherent to the PE guideline. CTPA scans were independently reported by two radiologists. RESULTS: During study period, 364 patients underwent CTPA to rule out PE, of which 125 (34.3%) had Wells' score > 4 (high probable risk) and 239 had Wells' score ≤ 4. Amongst low probable risk patients (Wells' score ≤ 4), only 32 patients had undergone the D-dimer test (23 patients had high level of D-dimer). Based on the algorithmic approach, patients with suspected PE, patients with high probability (125 patients), and patients with low probability with elevated D-dimer level (23 patients) were considered as adherent to the PE guideline; consequently, the total adherence to PE guideline was 148 out of 364 (40.6%). CONCLUSION: We followed the algorithmic approach guideline in about 40.0% of cases; however, we should pay more attention to the algorithmic approach in patients with suspected PE.

Technical and Clinical Factors Affecting Success Rate of a Deep Learning Method for Pancreas Segmentation on CT.

PURPOSE: Accurate pancreas segmentation has application in surgical planning, assessment of diabetes, and detection and analysis of pancreatic tumors. Factors that affect pancreas segmentation accuracy have not been previously reported. The purpose of this study is to identify technical and clinical factors that adversely affect the accuracy of pancreas segmentation on CT. METHOD AND MATERIALS: In this IRB and HIPAA compliant study, a deep convolutional neural network was used for pancreas segmentation in a publicly available archive of 82 portal-venous phase abdominal CT scans of 53 men and 29 women. The accuracies of the segmentations were evaluated by the Dice similarity coefficient (DSC). The DSC was then correlated with demographic and clinical data (age, gender, height, weight, body mass index), CT technical factors (image pixel size, slice thickness, presence or absence of oral contrast), and CT imaging findings (volume and attenuation of pancreas, visceral abdominal fat, and CT attenuation of the structures within a 5 mm neighborhood of the pancreas). RESULTS: The average DSC was 78% ± 8%. Factors that were statistically significantly correlated with DSC included body mass index (r = 0.34, p < 0.01), visceral abdominal fat (r = 0.51, p < 0.0001), volume of the pancreas (r = 0.41, p = 0.001), standard deviation of CT attenuation within the pancreas (r = 0.30, p = 0.01), and median and average CT attenuation in the immediate neighborhood of the pancreas (r = -0.53, p < 0.0001 and r = -0.52, p < 0.0001). There were no significant correlations between the DSC and the height, gender, or mean CT attenuation of the pancreas. CONCLUSION: Increased visceral abdominal fat and accumulation of fat within or around the pancreas are major factors associated with more accurate segmentation of the pancreas. Potential applications of our findings include assessment of pancreas segmentation difficulty of a particular scan or dataset and identification of methods that work better for more challenging pancreas segmentations.

Augmented Radiologist Workflow Improves Report Value and Saves Time: A Potential Model for Implementation of Artificial Intelligence.

RATIONALE AND OBJECTIVES: Our primary aim was to improve radiology reports by increasing concordance of target lesion measurements with oncology records using radiology preprocessors (RP). Faster notification of incidental actionable findings to referring clinicians and clinical radiologist exam interpretation time savings with RPs quantifying tumor burden were also assessed. MATERIALS AND METHODS: In this prospective quality improvement initiative, RPs annotated lesions before radiologist interpretation of CT exams. Clinical radiologists then hyperlinked approved measurements into interactive reports during interpretations. RPs evaluated concordance with our tumor measurement radiologist, the determinant of tumor burden. Actionable finding detection and notification times were also deduced. Clinical radiologist interpretation times were calculated from established average CT chest, abdomen, and pelvis interpretation times. RESULTS: RPs assessed 1287 body CT exams with 812 follow-up CT chest, abdomen, and pelvis studies; 95 (11.7%) of which had 241 verified target lesions. There was improved concordance (67.8% vs. 22.5%) of target lesion measurements. RPs detected 93.1% incidental actionable findings with faster clinician notification by a median time of 1 hour (range: 15 minutes-16 hours). Radiologist exam interpretation times decreased by 37%. CONCLUSIONS: This workflow resulted in three-fold improved target lesion measurement concordance with oncology records, earlier detection and faster notification of incidental actionable findings to referring clinicians, and decreased exam interpretation times for clinical radiologists. These findings demonstrate potential roles for automation (such as AI) to improve report value, worklist prioritization, and patient care.

Effect of low-level laser therapy on fracture healing in rabbits.

BACKGROUND AND AIMS: The purpose of this study was to investigate the effect of low-level laser therapy (LLLT) on radial bone fracture gap healing in a rabbit model. MATERIALS SUBJECTS AND METHODS: Thirty male white New Zealand rabbits under general anesthesia had a 3mm slice of radial bone surgically removed. Fifteen rabbits were treated by 830 nm laser at 4 J/cm2 and 15 were used as non-treated controls. Callus development was assessed by X-ray and radiographs every 7 days for 3 weeks. RESULTS: Significant radiologic changes were observed in both groups against time (P > 0.001) or from week to week (P > 0.05). However, there was no statistical difference in radiologic scores after week 2 (P = 0.087) or week 3 (P = 0.077) between control and laser treated bone. CONCLUSIONS: Findings suggest that in this study, laser treatment did not enhance callus formation nor reduce repair time of complete fracture of the radius in rabbits.

ENABLE (Exportable Notation and Bookmark List Engine): an Interface to Manage Tumor Measurement Data from PACS to Cancer Databases.

Oncologists evaluate therapeutic response in cancer trials based on tumor quantification following selected "target" lesions over time. At our cancer center, a majority of oncologists use Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 quantifying tumor progression based on lesion measurements on imaging. Currently, our oncologists handwrite tumor measurements, followed by multiple manual data transfers; however, our Picture Archiving Communication System (PACS) (Carestream Health, Rochester, NY) has the ability to export tumor measurements, making it possible to manage tumor metadata digitally. We developed an interface, "Exportable Notation and Bookmark List Engine" (ENABLE), which produces prepopulated RECIST v1.1 worksheets and compiles cohort data and data models from PACS measurement data, thus eliminating handwriting and manual data transcription. We compared RECIST v1.1 data from eight patients (16 computed tomography exams) enrolled in an IRB-approved therapeutic trial with ENABLE outputs: 10 data fields with a total of 194 data points. All data in ENABLE's output matched with the existing data. Seven staff were taught how to use the interface with a 5-min explanatory instructional video. All were able to use ENABLE successfully without additional guidance. We additionally assessed 42 metastatic genitourinary cancer patients with available RECIST data within PACS to produce a best response waterfall plot. ENABLE manages tumor measurements and associated metadata exported from PACS, producing forms and data models compatible with cancer databases, obviating handwriting and the manual re-entry of data. Automation should reduce transcription errors and improve efficiency and the auditing process.

Management of epilepsy in resource-limited areas: establishing an epilepsy surgery program in Iran.

Background Of about 40 million people with epilepsy, who live in developing countries, the majority do not receive appropriate treatment. Nonetheless, there are striking disparities among the so-called developing countries, however generally speaking, access to and availability of epilepsy management programs in developing countries are very limited and therefore, the issue of developing epilepsy centers in resource-limited settings in a large scale is very essential. The surgery for epilepsy, including temporal lobotomy, lesionectomy and corpus colostomy, for patients with medically-refractory seizures, defined as failure of adequate trials of two tolerated, appropriately chosen and using antiepileptic drug to achieve sustained freedom, from seizure has been proved to be feasible and cost-effective in developing countries. However, the success of epilepsy surgery depends upon the accurate identification of good surgical candidates based on the available resources and technologies without jeopardizing safety. In the current paper, we will share our experiences of establishing an epilepsy surgery program in Iran, despite all short-comings and limitations and try to provide some answers to those challenges, which helped us establish our program.

Frequency of cholelithiasis in patients with Beta-thalassemia intermedia with and without hydroxyurea.

BACKGROUND: Recent studies regarding the effect of hydroxyurea (HU) in thalassemia have revealed favorable effects on the reduction of ineffective erythropoiesis. OBJECTIVES: The aim of the current study was to evaluate whether or not HU can have an effect on the gallstone formation rate in patients with beta-thalassemia intermedia (BTI). PATIENTS AND METHODS: In this case control cross-sectional study, from a total of 250 transfusion-independent BTI patients, 51 patients who were taking HU, participated in the study. Patients were registered in the Thalassemia clinic of Shiraz University of Medical Sciences, Shiraz, which is a referral center located in southern Iran, during 2011-2012. Mean dose of HU consumption in the case group was 10 ± 2.5 mg/kg/day (range of 8-15 mg/kg/day), with a mean duration of consumption of 7.5 ± 3.8 years (range 1-14 years). In addition, 41 age- and sex-matched BTI patients who did not use HU were randomly selected as a control group. All patients underwent abdominal ultrasound by a radiologist for evaluation of gallstones. RESULTS: Mean age of the participants was 21.4 ± 6.5 years (10-40 years). There was no statistically significant difference regarding the frequency of cholelithiasis between the two groups of patients (P = 0.822). Our study showed significantly lower hemoglobin levels and a higher percentage of nucleated red blood cells in the HU group compared with the control group (P = 0.001 and P = 0.005, respectively). CONCLUSIONS: It seems that taking HU for long periods can reduce hemolysis and bone marrow suppression, and that decreases the rate of cholelithiasis. We believe that if these patients had not been treated with HU, we would probably have observed a significantly higher frequency of cholelithiasis, due to more hemolysis compared with patients not taking HU. Further studies with larger sample sizes are suggested.

An effective method for segmentation of MR brain images using the ant colony optimization algorithm.

Since segmentation of magnetic resonance images is one of the most important initial steps in brain magnetic resonance image processing, success in this part has a great influence on the quality of outcomes of subsequent steps. In the past few decades, numerous methods have been introduced for classification of such images, but typically they perform well only on a specific subset of images, do not generalize well to other image sets, and have poor computational performance. In this study, we provided a method for segmentation of magnetic resonance images of the brain that despite its simplicity has a high accuracy. We compare the performance of our proposed algorithm with similar evolutionary algorithms on a pixel-by-pixel basis. Our algorithm is tested across varying sets of magnetic resonance images and demonstrates high speed and accuracy. It should be noted that in initial steps, the algorithm is computationally intensive requiring a large number of calculations; however, in subsequent steps of the search process, the number is reduced with the segmentation focused only in the target area.

Artifacts in magnetic resonance imaging after surgical resection of brain tumors.

BACKGROUND: Since the advent of magnetic resonance imaging, metal artifacts have posed an important diagnostic problem in different fields of medicine. However, this has not been systematically studied in patients undergoing surgery for brain tumors. OBJECTIVE: This study was planned to assess whether metal artifacts can occur in patients undergoing brain surgery without metallic implants. METHODS: Of 40 individuals who could be included because of having a pre- and postoperative MRI and a postoperative computed tomography (CT) scan or a conventional skull X-ray for the detection of metallic artifacts, 26 patients agreed to participate in this study and gave informed consent. RESULTS: Twenty-six subjects, 12 males and 14 females, with an age range of 12 to 54 years, were included in the study. Four patients were found to have gross metal particles in their postoperative brain CTs and were excluded. Of the remaining 22 subjects, 7 patients (31.8%) had metallic artifacts. CONCLUSION: Our study showed that simple bone drilling or chiseling during surgical manipulation of skull bones may result in separation of very tiny metal particles which can remain in the surgical site and cause artifacts in postoperative MRIs. This finding appeared to be independent of factors such as age, sex, tumor/incision site, tumor size, pathologic tumor type, total radiation dose, operation-MRI time interval and sequence of MRI.

Frequency and distribution of asymptomatic brain lesions in patients with ß-thalassemia intermedia.

We aimed to determine the frequency of asymptomatic brain lesions in a group of patients with ß-thalassemia intermedia (ß-TI) and to evaluate correlation of asymptomatic brain lesions with splenectomy, thrombocytosis, blood transfusions, and clinical parameters. Ninety five neurologically intact patients with ß-TI were randomly enrolled in this cross-sectional study. Diffusion-weighted imaging brain MRI was performed in every patient to detect cerebral white matter lesions (WML). We found an overall frequency of 15 (15.8 %) for WMLs, 14 (23.7 %) in splenectomized, and 1 (2.8 %) in nonsplenectomized patients. The presence of WML was significantly associated with splenectomy (P = 0.008) and thrombocytosis (P = 0.009). However, after adjustment for splenectomy, thrombocytosis was not significantly associated with the presence of WML (P > 0.05). The number of patients with regular blood transfusions and normal MRI was not significantly higher compared to those with abnormal findings (52.5 % vs. 26.7 %; P = 0.092). In untransfused patients, hydroxyurea (HU) administration was associated with a lower incidence of WML (P < 0.001). Although in univariate analysis either splenectomy or thrombocytosis showed significant correlation with the presence of single or multiple WMLs, thrombocytosis by itself did not significantly contribute in developing asymptomatic brain lesions. The lack of significant correlation between lesions and regular blood transfusions could be related to the treatment with HU in untransfused patients, which increased fetal hemoglobin levels and improved the morphology and the pathological indices of the red blood cells. Larger prospective studies are suggested for the accurate evaluation of the correlation of these factors with developing asymptomatic brain lesions.

Micro and nanoparticle deposition in human nasal passage pre and post virtual maxillary sinus endoscopic surgery.

Realistic 3-D models of the human nasal passages were developed pre and post virtual uncinectomy and Middle Meatal Antrostomy. A 3-D computational domain was constructed by a series of coronal CT scan images from a healthy subject. Then a virtual uncinectomy intervention and maxillary antrostomy were performed on the left nasal passage by removing the uncinate process and exposing the maxillary sinus antrum. For several breathing rates corresponding to low or moderate activities, the airflows in the nasal passages were simulated numerically pre and post virtual routine maxillary sinus endoscopic surgery. The airflow distribution in the nasal airway, maxillary and frontal sinuses were analyzed and compared between pre and post surgery cases. A Lagrangian trajectory analysis approach was used for evaluating the path and deposition of microparticles in the nasal passages and maxillary sinuses. A diffusion model was used for nanoparticle transport and deposition analysis. The deposition rate of the inhaled micro and nanoparticles in the sinuses were evaluated and compared for pre and post operation conditions. The results showed that after maxillary sinus endoscopic surgery, the inhaled nano and microparticles can easily enter this sinus due to penetration of the airflow into the sinus cavity. This was in contrast to the preoperative condition in which almost no particles entered the sinuses. These results could be of importance for a better understanding of the effect of sinus endoscopic surgery on patient exposure to particulate pollution and inhalation drug delivery. The significantly higher airflow rate and particle deposition in the sinus could be a reason for the discomfort reported by some patient after maxillary sinus endoscopic surgery.

Metallic artifact in MRI after removal of orthopedic implants.

OBJECTIVE: The aim of the present study was to evaluate the metallic artifacts in MRI of the orthopedic patients after removal of metallic implants. SUBJECTS AND METHODS: From March to August 2009, 40 orthopedic patients operated for removal of orthopedic metallic implants were studied by post-operative MRI from the site of removal of implants. A grading scale of 0-3 was assigned for artifact in MR images whereby 0 was considered no artifact; and I-III were considered mild, moderate, and severe metallic artifacts, respectively. These grading records were correlated with other variables including the type, size, number, and composition of metallic devices; and the site and duration of orthopedic devices stay in the body. RESULTS: Metallic susceptibly artifacts were detected in MRI of 18 of 40 cases (45%). Screws and pins in removed hardware were the most important factors for causing artifacts in MRI. The artifacts were found more frequently in the patients who had more screws and pins in the removed implants. Gender, age, site of implantation of the device, length of the hardware, composition of the metallic implants (stainless steel versus titanium), and duration of implantation of the hardware exerted no effect in producing metallic artifacts after removal of implants. Short TE sequences of MRI (such as T1 weighted) showed fewer artifacts. CONCLUSION: Susceptibility of metallic artifacts is a frequent phenomenon in MRI of patients upon removal of metallic orthopedic implants.

Developing Criteria for Lumbar Spine Magnetic Resonance Imaging (MRI) Using RAND Appropriateness Method (RAM).

BACKGROUND: Studies show that a large proportion of healthcare offered may be inappropriate or unnecessary. Magnetic resonance imaging (MRI) is a new and expensive diagnostic technology which has been increasingly used all over the world. Moreover, this trend has been more rapidly increasing in Iran. Low back pain is a common disorder all over the world and MRI technique is one of the several ways to assess its cause. OBJECTIVES: The present study aims to develop scenarios for lumbar spine MRI. MATERIALS AND METHODS: In the present study, the RAND Appropriateness Method (RAM) was used in order to reach consensus regarding developing scenarios for lumbar spine MRI. We generated scenarios from valid clinical guidelines as well as the experts' opinion. The panel members included nine specialists from various medical specialties that had scored scenarios in two rounds, the first of which was without interaction, while the second one was with interaction. RESULTS: We extracted 97 scenarios for the lumbar spine MRI in the scenario extracting phase of the study and the panel members added 18 scenarios. After implementation of two rounds, the scenarios were categorized into three ranges. Sixty seven (58%) of the scenarios were considered as appropriate, 45 (39%) as uncertain, and three (2.6%) as inappropriate. CONCLUSIONS: RAM is useful for identifying stakeholder views in settings with limited resources. Since RAM has precise instructions for consensus developing, a large number of scenarios were considered as uncertain. Therefore, more research has to be conducted on the issue.

Effects of Melissa officinalis L. on oxidative status and DNA damage in subjects exposed to long-term low-dose ionizing radiation.

The aim of this study was to determine the capability of Melissa officinalis L. (Lemon balm) infusion on improvement of oxidative stress status in radiology staff that were exposed to persistent low-dose radiation during work. The study was a before-after clinical trial performed on 55 radiology staff. They were asked to drink Lemon balm infusion which was prepared like a tea bag twice daily (1.5 g/100 mL) for 30 days. In the plasma, lipid peroxidation, DNA damage, catalase, superoxide dismutase, myeloperoxidase, and glutathione peroxidase activity were measured before and after using Lemon balm infusion.Use of Lemon balm infusion in radiology unit workers resulted in a significant improvement in plasma levels of catalase, superoxide dismutase, and glutathione peroxidase and a marked reduction in plasma DNA damage, myeloperoxidase, and lipid peroxidation. It is concluded that infusion of Lemon balm markedly improve oxidative stress condition and DNA damage in radiology staff when used as a dietary supplement for radiation protection.