Publications by authors named "Mohammad Bagheri"

82 Publications

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.

Oncologist 2021 Feb 17. Epub 2021 Feb 17.

Genitourinary Malignancies Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.

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.

Methods: Adults with locally advanced, unresectable chordoma were treated on a randomized, placebo-controlled trial. Patients received 3 doses of GI-6301 (80 x 10 yeast cells) or placebo followed by radiation, followed by continued vaccine or placebo until progression. Primary endpoint was overall response rate, defined as a CR or 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 2 study in chordoma. There was 1 PR in each arm; no CRs were observed. Median PFS for vaccine and placebo arms was 20.6 months (95% 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. Pre-existing 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.
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http://dx.doi.org/10.1002/onco.13720DOI Listing
February 2021

Subepithelial Lesion in Bulb with Gastric Outlet Obstruction.

Middle East J Dig Dis 2020 Oct;12(4):288-291

MSc. of Health Information Technology, Tehran University of Medical Sciences, Tehran, Iran.

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http://dx.doi.org/10.34172/mejdd.2020.196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859608PMC
October 2020

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

Nat Med 2021 Feb 8. Epub 2021 Feb 8.

Genitourinary Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

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 × 10 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.
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http://dx.doi.org/10.1038/s41591-020-01225-1DOI Listing
February 2021

Glucose-6-phosphate dehydrogenase deficiency and SARS-CoV-2 mortality: Is there a link and what should we do?

Clin Biochem 2020 Dec 17;86:31-33. Epub 2020 Sep 17.

Division of Translational Medicine, Baqiyatallah Hospital, Baqiyatallah University of Medical Sciences, Tehran, Iran; Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran. Electronic address:

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http://dx.doi.org/10.1016/j.clinbiochem.2020.09.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7497541PMC
December 2020

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

J Clin Oncol 2020 11 11;38(31):3672-3684. Epub 2020 Sep 11.

Division of Medical Oncology, Department of Internal Medicine, College of Medicine, The Ohio State University, and the Comprehensive Cancer Center, Columbus, OH.

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.
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http://dx.doi.org/10.1200/JCO.20.01652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605393PMC
November 2020

Tissue Plasminogen Activator Loaded PCL Nanofibrous Scaffold Promoted Nerve Regeneration After Sciatic Nerve Transection in Male Rats.

Neurotox Res 2020 Aug 27. Epub 2020 Aug 27.

Hearing Disorders Research Center, Loghman Hakim Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

According to the studies, damages to the peripheral nerve as a result of a trauma or acute compression, stretching, or burns accounts for a vast range of discomforts which strongly impressed the patient's life quality. Applying highly potent biomolecules and growth factors in the damaged nerve site would promote the probability of nerve regeneration and functional recovery. Tissue plasminogen activator (tPA) is one of the components that can contribute importantly to degenerating and regenerating the peripheral nerves following the injuries occurred and the absence of this biomolecule hinders the recoveries of the nerves. This technique would guarantee the direct accessibility of tPA for the regenerating axons. Structural, physical, and in vitro cytotoxicity evaluations were done before in vivo experiments. In this study, twenty-four mature male rats have been exploited. The rats have been classified into four groups: controls, axotomy, axotomy + scaffold, and axotomy + tPA-loaded scaffold. Four, 8, and 12 weeks post-surgical, the sciatic functional index (SFI) has been measured. After 12 weeks, the spinal cord, sciatic nerve, and dorsal root ganglion specimens have been removed and stereological procedures, immunohistochemistry, and gene expression have been used to analyze them. Stereological parameters, immunohistochemistry of GFAP, and gene expression of S100, NGF, and BDNF were significantly enhanced in tPA-loaded scaffold group compared with axotomy group. The most similarity was observed between the results of control group and tPA-loaded scaffold group. According to the results, a good regeneration of the functional nerve tissues in a short time was observed as a result of introducing tPA.
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http://dx.doi.org/10.1007/s12640-020-00276-zDOI Listing
August 2020

Fixation of distal tibia fracture through plating, nailing, and nailing with Poller screws: A comparative biomechanical-based experimental and numerical investigation.

Proc Inst Mech Eng H 2020 Oct 10;234(10):1129-1138. Epub 2020 Jul 10.

Department of Orthopedic, Tehran University of Medical Sciences, Tehran, Iran.

The goal of this study was to investigate two commonly used methods of fixation of distal metaphyseal tibia fractures, plating and nailing as well as the less frequently employed nailing with Poller screws, from a biomechanical perspective. Despite numerous studies, the best method to repair fractures of tibia the remains up for of debate. This study includes an in vitro experimental phase on human cadaveric tibias followed by a finite element analysis. In the experimental phase, under partial weight-bearing axial loading, the axial stiffness of the bone-implant construct and interfragmentary movements for each of the fixation methods, bone-plate, bone-nail, and bone-nail-Poller screw, were measured and compared with each other. Shear interfragmentary movement and stress distribution in the bone-implant construct for the three mentioned fixation methods were also determined from FE models and compared with each other. Results of in vitro experiments, i.e., the exertion of axial loading on the tibia-plate, tibia-nail, and tibia-nail-Poller screw, showed that utilization of tibia-nail and tibia-nail-Poller screw led to a stiffer bone-implant construct, and consequently, lower interfragmentary movement, compared to the tibia-plate construct ( values for tibia-nail and tibia-nail-Poller screw, and for both axial stiffness and interfragmentary movement, compared to those of tibia-plate construct, were less than 0.05). Numerical analyses showed that nailing produced less undesirable shear interfragmentary movement, compared to the plating, and application of a Poller screw decreased the shear movements, compared to tibia-nail. Furthermore, using the finite element analysis, maximum von Mises stress of adding a screw in tibia-nail, tibia-plate, and tibia-nail-Poller screw, was found to be: 51.5, 78.6, and 60.5 MPa, respectively. The results of this study suggested that from a biomechanical standpoint, nailing both with and without a Poller screw is superior to plating for the treatment of distal tibia fractures.
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http://dx.doi.org/10.1177/0954411920941664DOI Listing
October 2020

A Rare Cause of Bowel Obstruction.

Middle East J Dig Dis 2020 Apr;12(2):133-135

Department of Surgery, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

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http://dx.doi.org/10.34172/mejdd.2020.175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320988PMC
April 2020

Combination of PARP Inhibitor Olaparib, and PD-L1 Inhibitor Durvalumab, in Recurrent Ovarian Cancer: a Proof-of-Concept Phase II Study.

Clin Cancer Res 2020 Aug 12;26(16):4268-4279. Epub 2020 May 12.

Women's Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.

Purpose: Preclinical studies suggest PARP inhibition (PARPi) induces immunostimulatory micromilieu in ovarian cancer thus complementing activity of immune checkpoint blockade. We conducted a phase II trial of PARPi olaparib and anti-PD-L1 durvalumab and collected paired fresh core biopsies and blood samples to test this hypothesis.

Patients And Methods: In a single-center, proof-of-concept phase II study, we enrolled women aged ≥18 with recurrent ovarian cancer. All patients were immune checkpoint inhibitor-naïve and had measurable disease per RECISTv1.1, ECOG performance status 0-2, and adequate organ and marrow function. Patients received olaparib 300 mg twice daily and durvalumab 1,500 mg intravenously every 4 weeks until disease progression, unacceptable toxicity, or withdrawal of consent. Primary endpoint was overall response rate (ORR). Secondary objectives were safety and progression-free survival (PFS). Translational objectives included biomarker evaluation for relationships with clinical response and immunomodulatory effects by treatment.

Results: Thirty-five patients with ovarian cancer [median, four prior therapies (IQR, 2-5.5), predominantly platinum-resistant (86%), wild-type (77%)] received at least one full cycle of treatment. ORR was 14% [5/35; 95% confidence interval (CI), 4.8%-30.3%]. Disease control rate (PR+SD) was 71% (25/35; 95% CI, 53.7%-85.4%). Treatment enhanced and expression, systemic IFNγ/TNFα production, and tumor-infiltrating lymphocytes, indicating an immunostimulatory environment. Increased IFNγ production was associated with improved PFS [HR, 0.37 (95% CI, 0.16-0.87), = 0.023], while elevated VEGFR3 levels were associated with worse PFS (HR, 3.22 (95% CI, 1.23-8.40), = 0.017].

Conclusions: The PARPi and anti-PD-L1 combination showed modest clinical activity in recurrent ovarian cancer. Our correlative study results suggest immunomodulatory effects by olaparib/durvalumab in patients and indicate that VEGF/VEGFR pathway blockade would be necessary for improved efficacy of the combination.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-0056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442720PMC
August 2020

Development of Evaluation System for Iranian Health Research Networks: Challenges and Lessons Learned.

Iran J Public Health 2020 Jan;49(1):104-113

Deputy of Research and Technology, Ministry of Health and Medical Education, Tehran, Iran.

Background: Health research networks (HRNs) are critical components of large-scale systems of production and validation of scientific evidence. As evaluation of research systems is a reliable process to measure efficiency and effectiveness of their activities, we aimed to report the processes of development of evaluation indicators' for Iranian health research networks and the results of conducted assessment.

Methods: In 2017, for the first time, aim to develop the evaluation framework for national HRNs, following the qualitative approach to assess the quality of research we designed the peer review method as one of the most important tools. This qualitative method was conducted according to experts' views in specific fields. Key policy makers and stakeholders collaboratively developed a number of criteria for evaluation of research performance of Iranian HRNs. Following the review of conducted studies, benefitting from published guide line, these indicators were defined under 4 main axes of governance and leadership; infrastructures; research products and research impact.

Results: Based on requirements of developed protocol for evaluation of HRNs in Iran, 18 HRNs completed the processes of evaluation. Results show a progressive need for more attention to precise planning of HRNs for achieving to goals. Another point to consider is the attention to documenting processes. The observational system for researches for detection of latest research priority was the most important issues that need to be more addressed by all of networks.

Conclusion: Research evaluation of Iranian HRNs more over creating of constructive positive competition provide an overview of the shortcomings and research challenges could be used for better planning and promotion of the health research system.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7152632PMC
January 2020

The in vivo effect of Lacto-N-neotetraose (LNnT) on the expression of type 2 immune response involved genes in the wound healing process.

Sci Rep 2020 01 22;10(1):997. Epub 2020 Jan 22.

Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Lacto-n-neotatraose (LNnT) oligosaccharide shows properties such as anti-inflammatory, type 2 immune response induction, induced angiogenesis, and anti-bacterial effects. Here, we hypothesized that the application of LnNT in the skin full-thickness wound can accelerate the healing process through its anti-inflammatory effect as well as induction of type 2 immune responses. In this study, we evaluated the cell viability of fibroblasts in the presence of LNnT. The full-thickness wound model was created by punch biopsy. The mice were treated intradermaly with LNnT at the concentrations of 100 and 200 µg or PBS as a control group. The wounds samples were compared based on the macroscopic and histological evaluations. The amount of collagen deposition and expression of genes involved in type 2 immunity were measured by the hydroxyproline assay and real time PCR method, respectively. Our results showed that LNnT had no negative effect on the cell viability of fibroblasts. LNnT increased the wound closure rate on day 7 post-wounding. H&E stain analysis revealed that mice treated with 200 µg LNnT exhibited better healing score, follicle formation, and lower epidermal thickness index. The mice treated with LNnT exhibited a lower collagen deposition on day 21 and higher collagen content on days 7 and 14 post-treatment. The LNnT groups also exhibited a lower number of neutrophils and a higher number of basal cells and fibroblasts. The expression rate of IL-10, IL-4, and IL-13 was higher in the LNnT groups. These results showed the high potential of LNnT for use in treatment of full-thickness wounds.
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http://dx.doi.org/10.1038/s41598-020-57860-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6976585PMC
January 2020

Combined effects of metformin and photobiomodulation improve the proliferation phase of wound healing in type 2 diabetic rats.

Biomed Pharmacother 2020 Mar 3;123:109776. Epub 2020 Jan 3.

Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Price Institute of Surgical Research, University of Louisville, Noveratech LLC of Louisville, Louisville, USA. Electronic address:

We determined the impact of Photobiomodulation (PBM) and metformin administration alone and combined on the inflammation and proliferation steps of wound healing of incisions in type two diabetes mellitus (T2DM) rats. 40 rats were divided into 4 groups (n = 10 each group). A non-genetic model of T2DM was induced in all rats, and an incision was made on each rat. There were 4 groups as follows: Group 1 was control group. Group 2 received PBM alone (890 nm, 80 Hz, 0.324 J/cm, daily). Group 3 received metformin alone (50 mg/kg, i.p., daily) and the fourth group received combination of PBM + metformin. At inflammation (day 4) and proliferation (day 7) steps, tensiometerical, stereological, and immunohistochemical examinations were performed. PBM and PBM + metformin treatments significantly increased wound strength at inflammation and proliferation steps of wound healing respectively. PBM, metformin, and PBM + metformin groups significantly decreased inflammatory cells at inflammation and proliferation steps of wound healing. PBM, metformin, and PBM + metformin groups significantly improved granulation tissue formation by increasing fibroblasts, and new blood vessel formation at inflammation and proliferation steps of wound healing. Metformin significantly increased M2 macrophages than other treatment groups at inflammation and proliferation steps of wound healing. Simultaneously, PBM significantly decreased M2 macrophages than control group. We concluded PBM and PBM + metformin treatments significantly hastened repair at the inflammation and proliferation steps of repairing skin injury in a non-genetic model of T2 DM. PBM + metformin showed a synergistic impact. There were not a positive relation between M2 macrophage number and wound strength in the studied groups. The details of the molecular mechanisms of PBM, and PBM + metformin treatments of repairing wounds in animals, and treatment of DFUs of patients with T2 DM should be elucidated by further research.
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http://dx.doi.org/10.1016/j.biopha.2019.109776DOI Listing
March 2020

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

Acad Radiol 2020 01;27(1):96-105

Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Building 10, 9000 Rockville Pike, Bethesda, MD 20892, USA.

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.
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http://dx.doi.org/10.1016/j.acra.2019.09.014DOI Listing
January 2020

Identifying the waist circumference of risk in people of African descent.

Nat Rev Endocrinol 2020 01;16(1):1-3

Clinical Image Processing Service, Department of Radiology and Imaging Services, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.

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http://dx.doi.org/10.1038/s41574-019-0289-0DOI Listing
January 2020

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

Acad Radiol 2020 05 16;27(5):689-695. Epub 2019 Sep 16.

Imaging Biomarkers and Computer-aided Diagnosis Laboratory, Radiology and Imaging Sciences Department, Clinical Center, National Institutes of Health, Building 10 Room 1C224D MSC 1182, Bethesda, MD 20892-1182. Electronic address:

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.
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http://dx.doi.org/10.1016/j.acra.2019.08.014DOI Listing
May 2020

Solitary rectal ulcer syndrome: addition of rectal therapies to biofeedback is more effective than biofeedback alone.

Gastroenterol Hepatol Bed Bench 2019 ;12(3):197-202

Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Aim: We designed this study to evaluate the effectiveness of the combination of topical rectal therapy with biofeedback in treatment of solitary rectal ulcer compared to single biofeedback therapy.

Background: Biofeedback therapy is an appropriate treatment for patients with solitary rectal ulcer syndrome (SRUS) but it seems that it is not effective alone. Topical medical therapies are supposed to have an additive role to biofeedback.

Methods: This randomized, controlled trial was conducted on 63 patients with SRUS. Patients were randomly enrolled into two groups of combination and single therapy. The patients in combination group (n=31) received biofeedback plus a topical therapy (an enema contained dexamethasone, sulfasalazine and bismuth) and the patients in single therapy group (n=32) were treated with biofeedback alone.

Results: Endoscopic responses to treatment in the combination and single groups were 80% and 50%, respectively (P<0.05). Clinical improvement in symptoms such as difficulty to evacuate, digitation to evacuate, feeling of incomplete evacuation, time to need to evacuation and life style alternation were significantly better in treated group by combination therapy than single therapy. Regarding to the mean total score based on all subjective parameters, the results were also significantly better in the treated group by combination therapy.

Conclusion: Topical anti-inflammatory therapies in combination with biofeedback is an efficient treatment for patients with SRUS.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668771PMC
January 2019

Talbot effect of azimuthally periodic Bessel-based structures.

Opt Lett 2019 Sep;44(17):4355-4358

In this work, the theory of self-imaging in the polar coordinates for azimuthally periodic Bessel-based structures (APBBSs) is presented. For the first time, to the best of our knowledge, we define single- and multi-frequency APBBSs and show that these structures have self-images under plane-wave illumination. We also define sinusoidal and binary-like single-frequency APBBSs and theoretically and experimentally investigate the near-field diffraction of these structures. The diffraction from these structures provides 2D arrays of optical traps that can be used in multi-trapping.
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http://dx.doi.org/10.1364/OL.44.004355DOI Listing
September 2019

Pharmacological prophylaxis versus pancreatic duct stenting plus pharmacological prophylaxis for prevention of post-ERCP pancreatitis in high risk patients: a randomized trial.

Endoscopy 2019 10 27;51(10):915-921. Epub 2019 Aug 27.

Liver and Pancreaticobiliary Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

Background: Acute pancreatitis is a serious complication of endoscopic retrograde cholangiopancreatography (ERCP). The aim of this noninferiority study was to evaluate the effectiveness of pancreatic duct (PD) stenting plus pharmacological prophylaxis vs. pharmacological prophylaxis alone in the prevention of post-ERCP pancreatitis (PEP) in high risk patients.

Methods: In this randomized, controlled, double-blind, noninferiority trial, patients at high risk of developing PEP were randomly allocated to pharmacological prophylaxis (rectal indomethacin, sublingual isosorbide dinitrate, and intravenous hydration with Ringer's lactate) plus PD stenting (group A) or pharmacological prophylaxis alone (group B). The rate and severity of PEP, serum amylase levels, and length of hospital stay after ERCP were assessed.

Results: During 21 months, a total of 414 patients (mean age 55.5 ± 17.0 years; 60.2 % female) were enrolled (207 in each group). PEP occurred in 59 patients (14.3 %, 95 % confidence interval [CI] 11.1 % - 17.9 %: 26 patients [12.6 %, 95 %CI 8.6 % - 17.6 %] in group A and 33 [15.9 %, 95 %CI 11.4 % - 21.4 %] in group B). There was no significant difference between the two groups in PEP severity ( = 0.59), amylase levels after 2 hours ( = 0.31) or 24 hours ( = 0.08), and length of hospital stay ( = 0.07).

Conclusions: The study failed to demonstrate noninferiority or inferiority of pharmacological prophylaxis alone compared with PD stenting plus pharmacological prophylaxis in the prevention of PEP in high risk patients.
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http://dx.doi.org/10.1055/a-0977-3119DOI Listing
October 2019

Human Bone Marrow Mesenchymal Stem Cell Conditioned Medium Promotes Wound Healing in Deep Second-Degree Burns in Male Rats.

Cells Tissues Organs 2018 24;206(6):317-329. Epub 2019 Jul 24.

Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran,

Burn wound treatment is difficult and one of the most challenging problems in the clinic. Researchers have examined the applications of mesenchymal stem cells as a cell-based therapy for skin regeneration. But the role of human bone marrow mesenchymal stem cell conditioned medium (hBM-MSC-CM) in the treatment of burn injury remains unclear. This research aims at detecting whether hBM-MSC-CM can increase the wound healing of deep second-degree burns in male rats. In this study, 32 adult male rats per each time point were randomly divided into four groups: (1) control group, (2) sham group (DMEM), (3) common treatment group (CT), and (4) conditioned media group (CM). A 3 × 3 cm circular burn was created on the back of the rats. On postsurgical days 7, 15, and 28, the wound closure area of each wound was measured and then the skin samples were removed and analyzed using stereological methods. Wound closure area was significantly increased in the CM and CT groups on the 15th and the 28th day after burn injury compared to the control and DMEM groups. The stereological parameters and immunohistochemistry analysis of the wounds revealed significantly improved healing in the CM group compared to the control and other groups. It is concluded that these findings indicate that hBM-MSC-CM promotes skin wound healing by increasing cell proliferation, regulating collagen synthesis and collagen composition, and inducing angiogenesis at the injury site.
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http://dx.doi.org/10.1159/000501651DOI Listing
July 2019

Impaired spermatogenesis associated with changes in spatial arrangement of Sertoli and spermatogonial cells following induced diabetes.

J Cell Biochem 2019 10 20;120(10):17312-17325. Epub 2019 May 20.

Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

The current study was conducted to assess the relationship between testicular cells in spermatogenesis, through which the production of healthy and mature sperm is essential. However, it seems necessary to obtain more information about the three-dimensional pattern of the testis cells arrangement, which is directly related to the function of the testis after induction of diabetes. Twelve adult mice (28-30 g) were assigned into two experimental groups: (1) control and (2) diabetic (40 mg/kg STZ). The epididymal sperm collected from the tail of the epididymis and testes samples were taken for stereology, immunocytochemistry and RNA extraction. Our data showed that diabetes could notably decrease the number of testicular cells, together with a reduction of total sperm count. In addition, the results from the second-order stereology indicated the significant changes in the spatial arrangement of Sertoli cells and spermatogonial cells in the diabetic groups, in comparison with the control (P < .05). Moreover, the immunohistochemistry results showed a significant reduction in Sex-determining Region Y (SRY) box 9 gene (SOX9), vimentin, occludin, and connexin-43 positive cells in the diabetic groups compared with the control (P < .05). Furthermore, our data showed that the expression of steroidogenic acute regulatory protein steroidogenic acute regulatory protein (StAR) and peripheral benzodiazepine receptor peripheral benzodiazepine receptor (PBR) was significantly reduced in the diabetic groups, in comparison with the control (P < .05). These findings suggest that structural and functional changes of testis cells after induction of diabetes cause the alterations in the spatial arrangement of Sertoli and spermatogonial cells, ultimately influencing the normal spermatogenesis in mice.
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http://dx.doi.org/10.1002/jcb.28995DOI Listing
October 2019

Lipid profile change after bariatric surgeries: laparoscopic gastric plication versus mini gastric bypass.

Acta Chir Belg 2019 Jun 19;119(3):146-151. Epub 2018 Nov 19.

d Students' Scientific Research Center, Tehran University of Medical Sciences , Tehran , Iran.

Introduction: Bariatric surgeries are known to have profound effects on lipid profile. Laparoscopic gastric plication (LGP) has been shown to have a comparable effect on weight loss rather than Roux-en-Y gastric bypass (RYGB) and mini gastric bypass (MGB). But the post-operative effect on lipid profile is not well-compared. We aimed to compare post-operative lipid profile change after LGP and MGB.

Methods: In a retrospective analysis, we reviewed 91 patients for at least 12 months. Patients were assigned to undergo either LGP (71 patients) or MGB (20 patients). Preoperative and postoperative visits were accomplished and weight, BMI, fasting blood glucose (FBG) and lipid profile including triglyceride (TG), and total cholesterol (TC) levels were repeatedly measured. Follow up rate for the first year was 100%.

Results: LGP significantly decreased both TG and TC levels in each follow up (all p values < .05). The same trends were observed in BMI reduction, total body weight loss percentage, and FBG. When comparing either TC or TG level between LGP and MGB, there was just one statistically significant result in TG reduction at 6 months (p value = .042) while MGB showed more reduction. All other variables in different follow up visits were not significantly different between two techniques.

Conclusions: LGP would result in lipid profile improvement lasting at least for one year. Lipid-lowering effect seems to be similar between LGP and MGB. This lipid-lowering property and weight reduction might be indicative that LGP is an alternative for RYGB and MGB in selective patients.
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http://dx.doi.org/10.1080/00015458.2018.1479022DOI Listing
June 2019

An improvement in acute wound healing in mice by the combined application of photobiomodulation and curcumin-loaded iron particles.

Lasers Med Sci 2019 Jun 5;34(4):779-791. Epub 2018 Nov 5.

Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, 1985717443, Iran.

Here, we examined the combined effect of pulse wave photobiomodulation (PBM) with curcumin-loaded superparamagnetic iron oxide (FeO) nanoparticles (curcumin), in an experimental mouse model of acute skin wound. Thirty male adult mice were randomly allocated into 5 groups. Group 1 was served as the control group. Group 2 was a placebo and received distilled water, as a carrier of curcumin. Group 3 received laser (890 nm, 80 Hz, 0.2 J/cm). Group 4 received curcumin by taking four injections around the wound. Group 5 received laser + curcumin. One full-thickness excisional round wound was made on the back of all the mice. On days 0, 4, 7, and 14, bacterial flora, wound surface area, and tensile strength were examined and microbiological examinations were performed. In case of wound closure, the two-way ANOVA shows that wound surface area of entire groups decreased progressively. However, the decrease in laser + curcumin and laser groups, and especially data from laser + curcumin group were statistically more significant, in comparison with the other groups (F statistics = 2.28, sig = 0.019). In terms of microbiology, the two-way ANOVA showed that laser, and laser + curcumin groups have statistically a lower bacterial count than the curcumin, control, and carrier groups (F statistics = 35, sig = 0 = 000). Finally, the one-way ANOVA showed that laser + curcumin, curcumin, and curcumin significantly increased wound strength, compared to the control and carrier groups. Furthermore, laser + curcumin significantly increased wound strength, compared to the control, laser, and curcumin groups (LSD test, p = 0.003, p = 0.002, and p = 0.005, respectively). In conclusion, curcumin nanoparticles, pulse wave laser, and pulse wave laser + curcumin nanoparticles accelerate wound healing, through a significant increase in wound closure rate, as well as wound strength, and a significant decrease in Staphylococcus aureus counts. Furthermore, the statistical analysis of our data suggests that the combined treatment of pulse wave laser + curcumin nanoparticles enhances the wound closure rate, and wound strength, compared to the laser and curcumin nanoparticles alone.
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http://dx.doi.org/10.1007/s10103-018-2664-9DOI Listing
June 2019

Effects of Photobiomodulation on Degranulation and Number of Mast Cells and Wound Strength in Skin Wound Healing of Streptozotocin-Induced Diabetic Rats.

Photomed Laser Surg 2018 Aug 6;36(8):415-423. Epub 2018 Jul 6.

7 Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran .

Background: A lack of effective treatments still exists for patients suffering from diabetes mellitus. Photobiomodulation is proved as a beneficial therapeutic modality for wounds.

Objective: The aim of this study is to examine the effect of degranulation of mast cells and total number of mast cells in the remodeling step of an ischemic model of wound healing under the influence of photobiomodulation and conditioned medium (CM) from human bone marrow-derived mesenchymal stem cells (hBM-MSCs-CM), or CM, administered alone and or in combination.

Materials And Methods: Initially, type 1 diabetes mellitus was induced in 72 male adult rats. Then, after a month, one incision was made on the back of each rat. Subsequently, the rats were divided into four groups. The first group was considered as the control (placebo) group, the second group received CM, the third group received photobiomodulation, and the fourth group received photobiomodulation+CM. On days 4, 7, and 15, samples were extracted from the wound for histological and tensiometric examinations. The total number of mast cells, including the three types of mast cells, was counted by the stereological methods. The tensiometric properties of the repairing tissue were examined.

Results: The administration of photobiomodulation and CM, alone or in combination, significantly increased the tensiometric properties within the healing wounds. Histologically, photobiomodulation+CM, CM, and photobiomodulation groups showed a significant decrease in the three types of mast cells and in the total number of mast cells compared with the control group on day 15.

Conclusions: We conclude that photobiomodulation and CM alone and or in combination significantly accelerated the healing process in a rat with a diabetic and ischemic wound, and significantly decreased the total number of mast cells and degranulation of mast cells. We suggest that the increased number of type 2 mast cells in the control group adversely affected the tensiometric properties of wounds in this group.
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http://dx.doi.org/10.1089/pho.2018.4453DOI Listing
August 2018

Vitamin B12 in Association with Antipsychotic Drugs Can Modulate the Expression of Pro-/Anti-Inflammatory Cytokines in Alzheimer Disease Patients.

Neuroimmunomodulation 2017 20;24(6):310-319. Epub 2018 Mar 20.

Immunology of Infectious Diseases Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.

Introduction: Patients with Alzheimer disease (AD) suffer from psychotic symptoms including pain. The current antipsychotic drugs confer limited effectiveness, and hence new strategies are being designed to decrease pain in order to increase antipsychological effectiveness. Vitamin B12 is a safe supplementary drug to decrease pain. Additionally, cytokines participate in the pathogenesis of immune-related diseases such as AD. Thus, the main aim of this clinical trial study was to determine the effects of treatment with risperidone and quetiapine, as antipsychotic drugs, with and without vitamin B12 on the psychotic symptoms of AD patients and the expression of IL-6, IL-8, tumor growth factor (TGF)-β, tumor necrosis factor (TNF)-α, and endothelin (ET)-1).

Material And Methods: Serum levels of IL-6, IL-8, TGF-β, TNF-α, and ET-1 were evaluated in the following groups: healthy controls, nonpsychotic AD patients, psychotic AD patients, psychotic AD patients under treatment with risperidone, psychotic AD patients under treatment with risperidone plus vitamin B12, psychotic AD patients under treatment with quetiapine, and psychotic AD patients under treatment with quetiapine plus vitamin B12.

Results: Treatment with antipsychotic drugs plus vitamin B12 led to a decreased expression of IL-8 and TNF-α and an increased expression of TGF-β. Vitamin B12 in association with quetiapine reduced the pain in psychotic AD patients.

Discussion: Proinflammatory cytokines play important roles in the pathogenesis of psychosis in AD patients. Antipsychotic drugs plus vitamin B12 can reduce and induce the expression of proinflammatory and anti-inflammatory cytokines to improve psychotic symptoms in AD patients.
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http://dx.doi.org/10.1159/000486597DOI Listing
January 2019

How to Assess Quality of Research in Iran, From Input to Impact? Introduction of Peer-Based Research Evaluation Model in Iran.

Arch Iran Med 2017 Nov 1;20(11):680-685. Epub 2017 Nov 1.

Deputy of Research and Technology, Ministry of Health and Medical Education, Tehran, Iran.

Background: Research evaluation is a systematic and objective process to measure relevance, efficiency and effectiveness of research activities, and peer review is one of the most important tools for assessing quality of research. The aim of this study was introducing research evaluation indicators based on peer reviewing.

Methods: This study was implemented in 4 stages. A list of objective-oriented evaluation indicators were designed in 4 axes, including; governance and leadership, structure, knowledge production and research impact.

Results: The top 10% medical sciences research centers (RCs) were evaluated based on peer review. Adequate equipment and laboratory instruments, high quality research publication and national or international cooperation were the main strengths in medical sciences RCs and the most important weaknesses included failure to adhere to strategic plans, parallel actions in similar fields, problems in manpower recruitment, knowledge translation & exchange (KTE) in service providers and policy makers' levels.

Conclusion: Peer review evaluation can improve the quality of research.
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November 2017

Role of Essential Oil of (Spearmint) in Addressing Reverse Hormonal and Folliculogenesis Disturbances in a Polycystic Ovarian Syndrome in a Rat Model.

Adv Pharm Bull 2017 Dec 31;7(4):651-654. Epub 2017 Dec 31.

Department of Anatomy, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

Given the antiandrogenic effects of spearmint, in this study we evaluated the effects of its essential oil on polycystic ovarian syndrome in a rat model. Female rats were treated as follows: Control, normal rats which received 150 mg/kg spearmint oil or 300 mg/kg spearmint oil, or sesame oil; and PCOS-induced rats which received 150 mg/kg spearmint oil or 300 mg/kg spearmint oil, or sesame oil. Then the animals were killed and the levels of LH, FSH, testosterone and ovarian folliculogenesis were evaluated. Spearmint oil reduced body weight, testosterone level, ovarian cysts and atretic follicles and increased Graafian follicles in PCOS rats. Spearmint has treatment potential on PCOS through inhibition of testosterone and restoration of follicular development in ovarian tissue.
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http://dx.doi.org/10.15171/apb.2017.078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5788221PMC
December 2017

Prexasertib, a cell cycle checkpoint kinase 1 and 2 inhibitor, in BRCA wild-type recurrent high-grade serous ovarian cancer: a first-in-class proof-of-concept phase 2 study.

Lancet Oncol 2018 02 18;19(2):207-215. Epub 2018 Jan 18.

Women's Malignancies Branch, National Cancer Institute, Bethesda, MD, USA.

Background: High-grade serous ovarian carcinoma is characterised by TP53 mutations, DNA repair defects, and genomic instability. We hypothesised that prexasertib (LY2606368), a cell cycle checkpoint kinase 1 and 2 inhibitor, would be active in BRCA wild-type disease.

Methods: In an open-label, single-centre, two-stage, proof-of-concept phase 2 study, we enrolled women aged 18 years or older with measurable, recurrent high-grade serous or high-grade endometrioid ovarian carcinoma. All patients had a negative family history of hereditary breast and ovarian cancer or known BRCA wild-type status, measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, Eastern Cooperative Oncology Group performance status score 0-2, and adequate haematological, renal, hepatic, and bone-marrow function. Patients received intravenous prexasertib 105 mg/m administered over 1 h every 14 days in 28-day cycles until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint of investigator-assessed tumour response, based on RECIST version 1.1, was assessed per protocol (assessable patients who had undergone CT imaging at baseline and attended at least one protocol-specified follow-up) and by intention to treat. The final analysis of this cohort of patients with BRCA wild-type high-grade serous ovarian carcinoma is reported here. This ongoing trial is registered with ClinicalTrials.gov, number NCT02203513, and continues to enrol patients for the BRCA-mutated ovarian cancer cohort.

Findings: Between Jan 20, 2015, and Nov 2, 2016, we enrolled 28 women with a median age of 64 years (IQR 58·0-69·5) who had previously received a median of 5·0 (IQR 2·5-5·0) systemic therapies. Most patients (22 [79%]) had platinum-resistant or platinum-refractory disease. All women received at least one dose of prexasertib, but four (14%) of 28 patients were not assessable for RECIST response. Eight (33%, 95% CI 16-55) of 24 patients assessable per protocol had partial responses. In the intention-to-treat population, eight (29%, 95% CI 13-49) of 28 had a partial responses. The most common (in >10% patients) grade 3 or 4 treatment-emergent adverse events were neutropenia in 26 (93%) of 28 patients, reduced white blood cell count in 23 (82%), thrombocytopenia in seven (25%), and anaemia in three (11%). Grade 4 neutropenia was reported in 22 (79%) patients after the first dose of prexasertib and was transient (median duration 6 days [IQR 4-8]) and recovered without growth-factor support in all cases. The treatment-related serious adverse event of grade 3 febrile neutropenia was reported in two (7%) patients. One patient died during the study due to tumour progression.

Interpretation: Prexasertib showed clinical activity and was tolerable in patients with BRCA wild-type high-grade serous ovarian carcinoma. This drug warrants further development in this setting, especially for patients with platinum-resistant or platinum-refractory disease.

Funding: Intramural Research Program of the National Institutes of Health and National Cancer Institute.
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http://dx.doi.org/10.1016/S1470-2045(18)30009-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366122PMC
February 2018

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

Laser Ther 2017 Sep;26(3):189-193

School of rehabilitation, Shiraz University of Medical Sciences, Shiraz, Iran.

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/cm 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.
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http://dx.doi.org/10.5978/islsm.17-OR-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5675909PMC
September 2017

Effects of Topical Tamoxifen on Wound Healing of Burned Skin in Rats.

Arch Plast Surg 2017 Sep 15;44(5):378-383. Epub 2017 Sep 15.

Trauma Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.

Background: This study aimed to assess the effects of the topical application of tamoxifen on wound healing of burned skin in Wistar rats by evaluating 3 healing characteristics: fibrotic tissue thickness (FTT), scar surface area (SSA), and angiogenesis in the healed scar tissue.

Methods: Eighteen male Wistar rats were used in this study. A third-degree burn wound was made on the shaved animals' back, measuring 2×2×2 cm. In the first group, a 2% tamoxifen ointment was applied to the wound twice daily for 8 weeks. The second group received a placebo ointment during the same period. The third group did not receive any treatment and served as the control group.

Results: The median (interquartile range=[Q1, Q3]) FTT was 1.35 (1.15, 1.62) mm, 1.00 (0.95, 1.02) mm, and 1.25 (0.8, 1.5) mm in the control, tamoxifen, and placebo groups, respectively (P=0.069). However, the FTT in the tamoxifen group was less than in the placebo and control groups. The median angiogenesis was 3.5 (3.00, 6.25), 8.00 (6.75, 9.25), and 7.00 (5.50, 8.25) vessels per high-power field for the control, tamoxifen, and placebo groups, respectively (P=0.067). However, the median angiogenesis was higher in the tamoxifen group than in the control group. No significant difference was observed in the mean SSA between the tamoxifen group and the control group (P=0.990).

Conclusions: Local application of tamoxifen increased angiogenesis and decreased the FTT, with no change in the SSA in burned skin areas. These effects are expected to expedite the wound healing process, reducing contracture and preventing hypertrophic scar and keloid formation.
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http://dx.doi.org/10.5999/aps.2017.44.5.378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5621812PMC
September 2017