Publications by authors named "Shervin Taslimi"

38 Publications

Antithrombotic choice in blunt cerebrovascular injuries: Experience at a tertiary trauma center, systematic review, and meta-analysis.

J Trauma Acute Care Surg 2021 Jul;91(1):e1-e12

From the Division of Neurosurgery (J.C.K., S.M.P., F.M., S.T., C.R.P., V.X.D.Y., L.d.C.), Sunnybrook Health Sciences Centre, University of Toronto, Toronto; Health Sciences North, Division of Neurosurgery (S.M.P.), Northern Ontario School of Medicine, Sudbury, ON; Biomedical Engineering, Faculty of Engineering (F.A.Z.), Department of Anatomy and Cell Science, Rady Faculty of Health Sciences (F.A.Z.), and Centre on Aging (F.A.Z.), University of Manitoba, Winnipeg, MA, Canada; Division of Anaesthesia, Department of Medicine (F.A.Z.), Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom; and Sunnybrook Health Sciences Centre, Department of Medical Imaging (M.M.), Sunnybrook Health Sciences Centre, Department of Surgery (A.N.), and Department of Medical Imaging, Sunnybrook Health Sciences Centre (L.d.C.), University of Toronto, Toronto, ON, Canada.

Background: Blunt cerebrovascular injuries (BCVIs) may occur following trauma and lead to ischemic stroke if untreated. Antithrombotic therapy decreases this risk; however, the optimal agent has yet to be determined in this population. The aim of this study was to compare the risk-benefit profile of antiplatelet (AP) versus anticoagulant (AC) therapy in rates of ischemic stroke and hemorrhagic complications in BCVI patients.

Methods: We performed a retrospective review of BCVI patients at our tertiary care Trauma hospital from 2010 to 2015, and a systematic review and meta-analysis of the literature. The OVID Medline, Embase, Web of Science, and Cochrane Library databases were searched from inception to September 16, 2019. References of included publications were searched manually for other relevant articles. The search was limited to articles in humans, in patients 18 years or older, and in English. Studies that reported treatment-stratified clinical outcomes following AP or AC treatment in BCVI patients were included. Exclusion criteria included case reports, case series with n < 5, review articles, conference abstracts, animal studies, and non-peer-reviewed publications. Data were extracted from each study independently by two reviewers, including study design, country of origin, sex and age of patients, Injury Severity Score, Biffl grade, type of treatment, ischemic stroke rate, and hemorrhage rate. Pooled estimates using odds ratio (OR) were combined using a random-effects model using a Mantel-Hanzel weighting. The main outcome of interest was rate of ischemic stroke due to BCVI, and the secondary outcome was hemorrhage rate based on AC or AP treatment.

Results: In total, there were 2044 BCVI patients, as reported in the 22 studies in combination with our institutional data. The stroke rate was not significantly different between the two treatment groups (OR, 1.27; 95% confidence interval, 0.40-3.99); however, the hemorrhage rate was decreased in AP versus AC treated groups (OR, 0.38; 95% confidence interval, 0.15-1.00).

Conclusion: Based on this meta-analysis, both AC and AP seem similarly effective in preventing ischemic stroke, but AP is better tolerated in the trauma population. This suggests that AP therapy may be preferred, but this should be further assessed with prospective randomized trials.

Level Of Evidence: Review article, level II.
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http://dx.doi.org/10.1097/TA.0000000000003194DOI Listing
July 2021

Lessons learned from contemporary glioblastoma randomized clinical trials through systematic review and network meta-analysis: part 2 newly diagnosed disease.

Neurooncol Adv 2021 Jan-Dec;3(1):vdab028. Epub 2021 Feb 12.

Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.

Background: Glioblastoma (GB) is the most common malignant brain tumor with a dismal prognosis despite standard of care (SOC). Here we used a network meta-analysis on treatments from randomized control trials (RCTs) to assess the effect on overall survival (OS) and progression-free survival (PFS) beyond the SOC.

Methods: We included RCTs that investigated the addition of a new treatment to the SOC in patients with newly diagnosed GB. Our primary outcome was OS, with secondary outcomes including PFS and adverse reactions. Hazard ratio (HR) and its 95% confidence interval (CI) regarding OS and PFS were extracted from each paper. We utilized a frequentist network meta-analysis. We planned a subgroup analysis based on O-methylguanine-DNA methyl-transferase () status. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses.

Results: Twenty-one studies were included representing a total of 7403 patients with GB. There was significant heterogeneity among studies impacting important factors such as timing of randomization and sample size. A confidence analysis on the network meta-analysis results revealed a score of low or very low for all treatment comparisons, across subgroups. Allowing for the heterogeneity within the study population, alkylating nitrosoureas (Lomustine and ACNU) and tumor-treating field improved both OS (HR = 0.53, 95% CI 0.33-0.84 and HR = 0.63 95% CI 0.42-0.94, respectively) and PFS (HR = 0.88, 95% CI 0.77-1.00 and HR = 0.63 95% CI 0.52-0.76, respectively).

Conclusions: Our analysis highlights the numerous studies performed on newly diagnosed GB, with no proven consensus treatment that is superior to the current SOC. Intertrial heterogeneity raises the need for better standardization in neuro-oncology studies.
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http://dx.doi.org/10.1093/noajnl/vdab028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134529PMC
February 2021

Lessons learned from contemporary glioblastoma randomized clinical trials through systematic review and network meta-analysis: part 2 recurrent glioblastoma.

Neurooncol Adv 2021 Jan-Dec;3(1):vdab029. Epub 2021 Feb 12.

Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.

Background: There exists no consensus standard of treatment for patients with recurrent glioblastoma (GB). Here we used a network meta-analysis on treatments from randomized control trials (RCTs) to assess the effect on overall survival (OS) and progression-free survival (PFS) to determine if any consensus treatment can be determined for recurrent GB.

Methods: We included all recurrent GB RCTs with at least 20 patients in each arm, and for whom patients underwent standard of care at the time of their GB initial diagnosis. Our primary outcome was OS, with secondary outcomes including PFS and adverse reactions. Hazard ratio (HR) and its 95% confidence interval (CI) of the comparison of study arms regarding OS and PFS were extracted from each paper. For comparative efficacy analysis, we utilized a frequentist network meta-analysis, an extension of the classic pair-wise meta-analysis. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses.

Results: Fifteen studies were included representing 29 separate treatment arms and 2194 patients. In our network meta-analysis, combination treatment with tumor-treating field and Vascular endothelial growth factor (VEGF) inhibitor ranked first in improving OS ( = .80). Concomitant anti-VEGF and Lomustine treatment was superior to Lomustine alone for extending PFS (HR 0.57, 95% CI 0.41-0.79) and ranked first in improving PFS compared to other included treatments ( = .86).

Conclusions: Our analysis highlights the numerous studies performed on recurrent GB, with no proven consensus treatment that is superior to the current SOC. Intertrial heterogeneity precludes drawing strong conclusions, and confidence analysis was low to very low. Further confirmation by future trials is recommended for our exploratory results.
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http://dx.doi.org/10.1093/noajnl/vdab029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134527PMC
February 2021

Optimal Management of Calvarial Lymphoma: A Meta-Analysis.

World Neurosurg 2021 Jul 24;151:e484-e494. Epub 2021 Apr 24.

Division of Neurosurgery, Department of Surgery, Kingston Health Sciences Centre, Queen's University, Kingston.

Background: Calvarial lymphoma is an exceedingly rare phenomenon; the clinical presentation and imaging pattern mimic many diseases of the central nervous system. Several treatment approaches have been undertaken with variable use of surgery plus adjuvant chemotherapy and radiation; an optimal treatment algorithm has yet to be defined. The aim of this study was to better characterize management strategies and patient outcomes.

Methods: An illustrative case was presented and a meta-analysis was carried out in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. MEDLINE and Embase were searched for cases of calvarial lymphoma. Outcomes between patients who underwent open surgery and biopsy only were compared directly.

Results: In an analysis from 1976 to 2019, 62 patients with a median age of 60 were included. The most common presentations were subcutaneous scalp mass (89%), headaches (26%), and focal neurological deficits (21%). Osteolytic changes on computed tomography were seen in 69% of patients with extension into either the intracranial or extracranial space in 97% of cases. Surgical excision was performed in 41 patients with a remission rate of 85% and a recurrence rate of 5%, which did not vary significantly from patients treated nonsurgically (remission in 75%, P = 0.479; recurrence in 0%, P = 1.000) CONCLUSIONS: In patients presenting with a progressively enlarging scalp mass, calvarial lymphoma should be in the differential diagnosis, as it can be effectively managed with a biopsy followed by chemotherapy and radiation. The role for open surgery may be limited.
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http://dx.doi.org/10.1016/j.wneu.2021.04.066DOI Listing
July 2021

In Reply to the Letter to the Editor Regarding "Acupuncture-Induced Cranial Epidural Abscess: Case Report and Review of the Literature".

World Neurosurg 2020 09;141:557

Sunnybrook Health Sciences Centre, Division of Neurosurgery, University of Toronto, Toronto, Ontario, Canada.

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http://dx.doi.org/10.1016/j.wneu.2020.06.112DOI Listing
September 2020

Determining the Optimal Adjuvant Therapy for Improving Survival in Elderly Patients with Glioblastoma: A Systematic Review and Network Meta-analysis.

Clin Cancer Res 2020 06 17;26(11):2664-2672. Epub 2020 Jan 17.

Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Canada.

Purpose: Older patients with glioblastoma (GBM) are underrepresented in clinical trials. Several abbreviated and standard chemoradiotherapy regimens are advocated with no consensus on the optimal approach. Our objective was to quantitatively evaluate which of these regimens would provide the most favorable survival outcomes in older patients with GBM using a network meta-analysis.

Experimental Design: MEDLINE, Embase, Google Scholar, and the Cochrane Library were searched. Patients >60 years of age with histologically confirmed GBM were included. Primary outcome of interest was the pooled HR from randomized controlled trials (RCTs). Secondary outcomes of interest included pooled HR from studies controlling for MGMT promoter methylation status, and safety.

Results: Fourteen studies, including 5 RCTs, reporting 4,561 patients were included. Using highest quality data from RCTs, our network-based approach demonstrated that standard radiotherapy (SRT) and temozolomide (TMZ) provided similar survival benefit when compared with hypofractionated radiotherapy (HRT) and TMZ [HR = 0.90; 95% confidence interval (CI), 0.43-1.87], TMZ alone (HR 1.25; 95% CI, 0.69-2.26), HRT alone (HR = 1.34; 95% CI, 0.73-2.45), or SRT alone (HR = 1.43; 95% CI, 0.87-2.36). HRT-TMZ had the highest probability (85%) of improving survival in older patients with GBM followed by SRT-TMZ (72%). Pooled analysis of trials controlling for promoter methylation status demonstrated that TMZ monotherapy confers similar survival benefit to combined chemoradiotherapy.

Conclusions: Statistical comparisons using a network approach demonstrates that the common treatment regimens for older patients with GBM in previous RCTs confer similar survival benefits. Adjustments for MGMT promoter methylation status demonstrated that radiotherapy alone was inferior to TMZ-based approaches. Head-to-head comparison of TMZ monotherapy to combined TMZ and radiation is warranted.
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http://dx.doi.org/10.1158/1078-0432.CCR-19-3359DOI Listing
June 2020

In reply to Letter to the Editor Regarding "Acupuncture-Induced Cranial Epidural Abscess: Case Report and Review of the Literature".

World Neurosurg 2019 12 19;132:444. Epub 2019 Nov 19.

Sunnybrook Health Sciences Centre, Division of Neurosurgery, University of Toronto, Ontario, Canada.

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http://dx.doi.org/10.1016/j.wneu.2019.08.156DOI Listing
December 2019

In Reply to the Letter to the Editor Regarding "Acupuncture-Induced Cranial Epidural Abscess: Case Report and Review of the Literature".

World Neurosurg 2019 07;127:655

Sunnybrook Health Sciences Centre, Division of Neurosurgery, University of Toronto, Toronto, Ontario, Canada.

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http://dx.doi.org/10.1016/j.wneu.2019.03.152DOI Listing
July 2019

Novel Statistical Analyses to Assess Hearing Outcomes After ABI Implantation in NF2 Patients: Systematic Review and Individualized Patient Data Analysis.

World Neurosurg 2019 Aug 3;128:e669-e682. Epub 2019 May 3.

Division of Neurosurgery, Department of Surgery, Sunnybrook Health Science Centre, Toronto, Ontario, Canada.

Background: Patients with neurofibromatosis type 2 develop bilateral vestibular schwannomas with progressive hearing loss. Auditory brainstem implants (ABIs) stimulate hearing in the cochlear nuclei and show promise in improving hearing. Here, we assess the impact of ABI on hearing over time by systematically reviewing the literature and re-analyzing available individual patient data.

Methods: A multidatabase search identified 3 studies with individual patient data of longitudinal hearing outcomes after ABI insertion in adults. Data were collected on hearing outcomes of different sound complexities from sound to speech using an ABI ± lip reading ability plus demographic data. Because of heterogeneity each study was analyzed separately using random effects multilevel mixed linear modeling.

Results: Across all 3 studies (n = 111 total) there were significant improvements in hearing over time from ABI placement (P < 0.000 in all). Improvements in comprehension of sounds, words, sentences, and speech occurred over time with ABI use + lip reading but lip reading ability did not improve over time. All categories of hearing complexity had over 50% comprehension after over 1 year of ABI use and some subsets had over 75% or near 100% comprehension. Vowel comprehension was greater than consonant, and word comprehension was greater than sentence comprehension (P < 0.0001 in both). Age and sex did not predict outcomes.

Conclusions: ABIs improve hearing beyond lip reading alone, which represents baseline patient function prior to treatment, and the benefits continue to improve with time. These findings may be used to guide patient counseling regarding ABI insertion, rehabilitation course after insertion, and future studies.
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http://dx.doi.org/10.1016/j.wneu.2019.04.232DOI Listing
August 2019

Hemorrhage, Seizures, and Dynamic Changes of Familial versus Nonfamilial Cavernous Malformation: Systematic Review and Meta-analysis.

World Neurosurg 2019 Jun 7;126:241-246. Epub 2019 Mar 7.

Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada; Division of Neurosurgery, Labatt Family Centre of Excellence in Brain Injury and Trauma Research, Keenan Research Centre for Biomedical Science, and Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada. Electronic address:

Background: Cerebral cavernous malformations (CCMs) may be familial or nonfamilial. This systematic review compared the natural history of CCMs in familial compared with nonfamilial cases.

Methods: We searched MEDLINE, Web of Science, and EMBASE for natural history studies on CCMs up to September 2018. We included studies that followed at least 20 untreated patients. Primary outcomes were hemorrhage, seizures, and neuroimaging changes in familial and nonfamilial cases. Incidence rate per person-year (PY) or lesion-year (LY) of follow-up were used to pool the data using fixed-effects or random-effects models. We used the incidence rate ratio for comparison.

Results: We could not compare hemorrhage rates between familial and nonfamilial cases mainly owing to mixtures of subgroups of patients. The seizure rate was similar in familial and nonfamilial cases with pooled incidence rate of 1.5%/PY (95% confidence interval 1.1%-2.2%). The reseizure rate was higher than the seizure rate (P < 0.001). New lesion development was higher in familial cases (32.1%/PY vs. 0.7%/PY, P < 0.001). Signal change on neuroimaging ranged from 0.2%/LY to 2.4%/LY in familial cases. In familial cases, incidence rate of size change was 8%/PY (95% confidence interval 5.2%-12.2%) and 1.1%/LY (95% confidence interval 0.6%-1.6%).

Conclusions: Familial CCMs show higher dynamic changes than nonfamilial cases. However, the presence of actual dynamic changes needs further assessment in nonfamilial cases. CCMs demonstrate a low incidence of seizure. First-time seizure increases the chance of recurrent seizure. Seizure rate based on the location and type of the lesion should be investigated further.
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http://dx.doi.org/10.1016/j.wneu.2019.02.115DOI Listing
June 2019

Acupuncture-Induced Cranial Epidural Abscess: Case Report and Review of the Literature.

World Neurosurg 2019 05 8;125:519-526.e1. Epub 2019 Feb 8.

Sunnybrook Health Sciences Centre, Division of Neurosurgery, University of Toronto, Toronto, Ontario, Canada.

Background: Acupuncture is a common form of alternative medicine that is used for pain control among other modalities of treatment. It is a relatively safe procedure, but complications, including those of infectious etiology, may still occur.

Case Description: A 47-year-old immunosuppressed woman presented with fever, altered level of consciousness, dysphasia, and a left occipital subgaleal fluctuant mass after acupuncture for headaches in the same area. Imaging demonstrated subgaleal and epidural collection localized in the left occipital region. She underwent urgent surgical evacuation of both collections. Cultures from intraoperative specimens grew Streptococcus anginosus. The patient started targeted antibiotic treatment leading to complete recovery.

Conclusions: To our knowledge, this is the first report of intracranial abscess after acupuncture. Given the worldwide application of this alternative treatment, physicians, acupuncturists, and the general public should be aware of the possibility of this rare but serious complication.
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http://dx.doi.org/10.1016/j.wneu.2019.01.189DOI Listing
May 2019

Surgical outcomes for medically intractable epilepsy in low- and middle-income countries: a systematic review and meta-analysis.

J Neurosurg 2018 Nov 1:1-11. Epub 2018 Nov 1.

9Division of Neurosurgery, The Hospital for Sick Children, Department of Surgery, University of Toronto, Ontario.

OBJECTIVEThe aim of this study was to describe the current state of epilepsy surgery and establish estimates of seizure outcomes following surgery for medically intractable epilepsy (MIE) in low- and middle-income countries (LMICs).METHODSThe MEDLINE and Embase databases were searched without publication date restriction. This search was supplemented by a manual screen of key epilepsy and neurosurgical journals (January 2005 to December 2016). Studies that reported outcomes for at least 10 patients of any age undergoing surgery for MIE in LMICs over a defined follow-up period were included. A meta-analysis with a random-effects model was performed in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement and MOOSE (Meta-analysis of Observational Studies in Epidemiology) guidelines. Pooled estimates of seizure freedom and favorable seizure outcomes following anterior temporal lobectomy with or without amygdalohippocampectomy (ATL ± AH) were reported.RESULTSTwenty studies were selected, of which 16 were from Asian centers. The average age at surgery in all studies was less than 30 years, and the average preoperative duration of epilepsy ranged from 3 to 16.1 years. Mesial temporal sclerosis accounted for 437 of 951 described pathologies, and 1294 of the 1773 procedures were ATL ± AH. Based on 7 studies (646 patients) the pooled seizure freedom estimate following ATL ± AH was 68% (95% CI 55%-82%). Based on 8 studies (1096 patients), the pooled estimate for favorable seizure outcomes was 79% (95% CI 74%-85%).CONCLUSIONSSurgery for MIE in LMICs shows a high percentage of seizure freedom and favorable outcomes. These findings call for a concerted global effort to improve timely access to surgery for MIE patients in these regions, including investments aimed at refining existing and establishing additional centers.
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http://dx.doi.org/10.3171/2018.5.JNS18599DOI Listing
November 2018

Chronic subdural collection overlying an intra-axial hemorrhagic lesion in chronic myelomonocytic leukemia: special report and review of the literature.

Expert Rev Neurother 2018 May 19;18(5):371-377. Epub 2018 Apr 19.

Department of Neurosurgery, Toronto Western Hospital, University of Toronto, Toronto, Canada.

: Chronic myelomonocytic leukaemia (CMML) is a clonal hematopoietic stem cell disorder characterized by the presence of an absolute monocytosis in the peripheral blood (>1 x 10/L) and the presence of myelodysplastic and myeloproliferative features in the bone marrow. Involvement of the central nervous system (CNS) is uncommon in CMML.: Herein described is a case report of a CMML patient who presents with symptomatic chronic subdural collection overlying a haemorrhagic brain lesion, along with diffuse dural infiltration, after two cycles of azacytidine. Surgical intervention was performed to alleviate the mass effect on the brain, and obtain a tissue sample for diagnosis. Histopathological report confirmed brain infiltration with myeloid leukemic cells.: Despite its rarity, cerebral dissemination should be considered even in patients with CMML. A multidisciplinary approach, lead by a hematologist, is mandatory in order to correct the underlying haematological disorder, with specific attention to the coagulation profile. Surgical intervention is necessary for symptomatic patients, and should be performed once an improvement of clinical conditions has been achieved. Despite appropriate surgical and medical therapy, the prognosis remains poor with high risk of perioperative complications, such as rebleeding, and progressive systemic involvement.
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http://dx.doi.org/10.1080/14737175.2018.1464391DOI Listing
May 2018

Deep brain stimulation for Parkinson's disease: meta-analysis of results of randomized trials at varying lengths of follow-up.

J Neurosurg 2018 04 30;128(4):1199-1213. Epub 2017 Jun 30.

1Division of Neurosurgery, Toronto Western Hospital, Department of Surgery, University of Toronto.

OBJECTIVE Deep brain stimulation (DBS) is effective in the management of patients with advanced Parkinson's disease (PD). While both the globus pallidus pars interna (GPi) and the subthalamic nucleus (STN) are accepted targets, their relative efficacy in randomized controlled trials (RCTs) has not been established beyond 12 months. The objective of this study was to conduct a meta-analysis of RCTs to compare outcomes among adults with PD undergoing DBS of GPi or STN at various time points, including 36 months of follow-up. METHODS The MEDLINE, Embase, CENTRAL, Web of Science, and CINAHL databases were searched. Registries for clinical trials, selected conference proceedings, and the table of contents for selected journals were also searched. Screens were conducted independently and in duplicate. Among the 623 studies initially identified (615 through database search, 7 through manual review of bibliographies, and 1 through a repeat screen of literature prior to submission), 19 underwent full-text review; 13 of these were included in the quantitative meta-analysis. Data were extracted independently and in duplicate. The Cochrane Collaboration tool was used to assess the risk of bias. The GRADE evidence profile tool was used to assess the quality of the evidence. Motor scores, medication dosage reduction, activities of daily living, depression, dyskinesias, and adverse events were compared. The influence of disease duration (a priori) and the proportion of male patients within a study (post hoc) were explored as potential subgroups. RESULTS Thirteen studies (6 original cohorts) were identified. No difference in motor scores or activities of daily living was identified at 36 months. Medications were significantly reduced with STN stimulation (5 studies, weighted mean difference [WMD] -365.46, 95% CI -599.48 to -131.44, p = 0.002). Beck Depression Inventory scores were significantly better with GPi stimulation (3 studies; WMD 2.53, 95% CI 0.99-4.06 p = 0.001). The motor benefits of GPi and STN DBS for PD are similar. CONCLUSIONS The motor benefits achieved with GPi and STN DBS for PD are similar. DBS of STN allows for a greater reduction of medication, but not as significant an advantage as DBS of GPi with respect to mood. This difference is sustained at 36 months. Further long-term studies are necessary.
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http://dx.doi.org/10.3171/2016.11.JNS16715DOI Listing
April 2018

Citation classics in neuro-oncology: assessment of historical trends and scientific progress.

Neuro Oncol 2017 Sep;19(9):1158-1172

Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Division of Neurosurgery, University of Toronto, Toronto, Ontario, Canada; Division of Neurosurgery, Sunnybrook Health Science Centre, Toronto, Ontario, Canada; Division of Neurosurgery, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada; MacFeeters Adult Brain Tumor Research Program, Toronto, Ontario, Canada.

Background: Citation classics represent the highest cited works in a field and are often regarded as the most influential literature. Analyzing thematic trends in citation classics across eras enables recognition of important historical advances within a field. We present the first analysis of the citation classics in neuro-oncology.

Methods: The Web of Science database was searched using terms relevant to "neuro-oncology." Articles with >400 citations were identified and the top 100 cited articles were evaluated.

Results: The top 100 neuro-oncology citation classics consisted of 43 clinical studies (17 retrospective, 10 prospective, 16 randomized trials), 43 laboratory investigations, 8 reviews/meta-analyses, and 6 guidelines/consensus statements. Articles were classified into 4 themes: 13 pertained to tumor classification, 37 to tumor pathogenesis/clinical presentation, 6 to imaging, 44 to therapy (15 chemotherapy, 10 radiotherapy, 5 surgery, 14 new agents). Gliomas were the most common tumor type examined, with 70 articles. There was a significant increase in the number of citation classics in the late 1990s, which was paralleled by an increase in studies examining tumor pathogenesis, chemotherapy, and new agents along with laboratory and randomized studies.

Conclusions: The majority of citation classics in neuro-oncology are related to gliomas and pertain to tumor pathogenesis and treatment. The rise in citation classics in recent years investigating tumor biology, new treatment agents, and chemotherapeutics may reflect increasing scientific interest in nonsurgical treatments for CNS tumors and the need for fundamental investigations into disease processes.
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http://dx.doi.org/10.1093/neuonc/nox053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5570246PMC
September 2017

Natural history of cavernous malformation: Systematic review and meta-analysis of 25 studies.

Neurology 2016 May 22;86(21):1984-91. Epub 2016 Apr 22.

From the Division of Neurosurgery (S.T.), University of Toronto, Canada; Department of Psychiatry (A.M.), Icahn School of Medicine, Mount Sinai Hospital, New York, NY; Department of Neurosurgery (S.A.-H.), University of Illinois at Chicago; Neurosurgical Service (F.G.B.), Massachusetts General Hospital, Harvard Medical School, Boston; Division of Neurosurgery (R.L.M.), St. Michael's Hospital, Labatt Family Centre of Excellence in Brain Injury and Trauma Research, Keenan Research Centre for Biomedical Science; and the Department of Surgery (R.L.M.), Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto, Canada.

Objective: We pooled the results of studies on natural history of cavernous malformations (CM) to calculate point estimates and investigate main sources of heterogeneity.

Methods: We searched MEDLINE, EMBASE, and ISI Web of Science for relevant studies published before May 2015. We used fixed or random effects models and meta-regression to pool the data.

Results: Twenty-five studies were entered into the meta-analysis (90-1,295 patients depending on the analysis). Bleeding was defined as symptomatic hemorrhage plus radiologic evidence of hemorrhage. Sources of heterogeneity were identified as mixture of hemorrhage and rehemorrhage, mixture of rehemorrhage before and after 2 years of first bleeding, brainstem vs other locations, and calculation method. The rehemorrhage rate was higher than the hemorrhage rate (incidence rate ratio 16.5, p < 0.001, 95% confidence interval [CI] 9.7-28.0). Rehemorrhage within 2 years of the first hemorrhage was higher than after that (incidence rate ratio 1.8, p = 0.042, 95% CI 1.5-2.0). In two metaregression models, rough estimate of the annual incidence rate of hemorrhage was 0.3% (95% CI 0.1%-0.5%) and 2.8% (2.5%-3.3%) per person year in nonbrainstem and brainstem lesions and rough estimate of annual rehemorrhage rate per person year was 6.3% (3%-13.2%) and 32.3% (19.8%-52.7%) in nonbrainstem and brainstem lesions. Median time to rehemorrhage was 10.5 months. Posthemorrhage full recovery was 38.8%/person-year (28.7%-48.8%). Posthemorrhage full recovery or minimal disability was 79.5%/person-year (74.3%-84.8%). Mortality after bleeding was 2.2%.

Conclusions: The incidence of symptomatic hemorrhage or rehemorrhage is higher in brainstem lesions. First symptomatic hemorrhage increases the chance of symptomatic rehemorrhage, which decreases after 2 years.
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http://dx.doi.org/10.1212/WNL.0000000000002701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4887121PMC
May 2016

Surgically resected skull base meningiomas demonstrate a divergent postoperative recurrence pattern compared with non-skull base meningiomas.

J Neurosurg 2016 08 1;125(2):431-40. Epub 2016 Jan 1.

Division of Neurosurgery, University of Toronto;

OBJECTIVE The objective of this study was to identify the natural history and clinical predictors of postoperative recurrence of skull base and non-skull base meningiomas. METHODS The authors performed a retrospective hospital-based study of all patients with meningioma referred to their institution from September 1993 to January 2014. The cohort constituted both patients with a first-time presentation and those with evidence of recurrence. Kaplan-Meier curves were constructed for analysis of recurrence and differences were assessed using the log-rank test. Cox proportional hazard regression was used to identify potential predictors of recurrence. RESULTS Overall, 398 intracranial meningiomas were reviewed, including 269 (68%) non-skull base and 129 (32%) skull base meningiomas (median follow-up 30.2 months, interquartile range [IQR] 8.5-76 months). The 10-year recurrence-free survival rates for patients with gross-total resection (GTR) and subtotal resection (STR) were 90% and 43%, respectively. Skull base tumors were associated with a lower proliferation index (0.041 vs 0.062, p = 0.001), higher likelihood of WHO Grade I (85.3% vs 69.1%, p = 0.003), and younger patient age (55.2 vs 58.3 years, p = 0.01). Meningiomas in all locations demonstrated an average recurrence rate of 30% at 100 months of follow-up. Subsequently, the recurrence of skull base meningiomas plateaued whereas non-skull base lesions had an 80% recurrence rate at 230 months follow-up (p = 0.02). On univariate analysis, a prior history of recurrence (p < 0.001), initial WHO grade following resection (p < 0.001), and the inability to obtain GTR (p < 0.001) were predictors of future recurrence. On multivariate analysis a prior history of recurrence (p = 0.02) and an STR (p < 0.01) were independent predictors of a recurrence. Assessing only patients with primary presentations, STR and WHO Grades II and III were independent predictors of recurrence (p < 0.001 for both). CONCLUSIONS Patients with skull base meningiomas present at a younger age and have less aggressive lesions overall. Extent of resection is a key predictor of recurrence and long-term follow-up of meningiomas is necessary, especially for non-skull base tumors. In skull base meningiomas, recurrence risk plateaus approximately 100 months after surgery, suggesting that for this specific cohort, follow-up after 100 months can be less frequent.
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http://dx.doi.org/10.3171/2015.7.JNS15546DOI Listing
August 2016

A Practical Methodological Approach Towards Identifying Core Competencies in Medical Education Based on Literature Trends: A Feasibility Study Based on Vestibular Schwannoma Science.

Neurosurgery 2015 Oct;77(4):594-602; discussion 602-3

*Division of Neurosurgery, University of Toronto, Toronto, Ontario; ‡Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario; §Division of Neurosurgery, King Saud University, Riyadh, Saudi Arabia; ¶Departments of Neurosurgery and ‖Radiation Oncology, NYU Langone Medical Center, New York University, New York.

Background: Competency-based medical education (CBME) is gaining momentum in postgraduate residency and fellowship training. While randomized trials, consensus statements, and practice guidelines can help delineate some of the core competencies for CBME, they are not applicable to all clinical scenarios.

Objective: To propose and assess the feasibility of a practical methodology for addressing this issue using radiosurgery for vestibular schwannoma (VS) science as an example.

Methods: The Web of Science electronic database was searched using relevant terms. A 3-step review of titles and abstracts was used. Studies were classified independently and in duplicate as either efficacy or effectiveness analyses. Cohen's kappa score was used to assess inter-rater agreement.

Results: Overall, 1818 surgical and 943 radiosurgical publications were identified. The number of effectiveness studies surpassed that of efficacy studies in the late 1980s for surgical studies, and in the early-to-mid 1990s among radiosurgical studies. The publication rate was higher for radiosurgery in the mid 1990s, but it paralleled that of surgical studies beyond the early 2000s. Variations in this overall trend corresponded to the emergence of studies that assessed the role of endoscopy and the utility of dose reduction in radiosurgery.

Conclusion: We have confirmed the feasibility and accuracy of this objective methodological approach. By understanding how the peer-reviewed literature reflects actual practice interests, educators can tailor curricula to ensure that trainees remain current. While further validation studies are needed, this methodology can serve as a supplemental strategy for identifying additional core competencies in CBME.
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http://dx.doi.org/10.1227/NEU.0000000000000837DOI Listing
October 2015

Seroprevalence of NMO-IgG Antibody in Neuromyelitis optica (NMO) and Its Specificity in Differentiating NMO from Other Demyelinating Diseases with Overlap Symptoms: An Iranian Experience.

Iran J Allergy Asthma Immunol 2015 Feb;14(1):98-104

Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

Neuromyelitis optica is an inflammatory demyelinating disease (IDD) of the CNS, which mainly affects optic nerve and spinal cord. Autoantibodies against aquaporin-4 also known as NMO-IgG have been implicated in the pathogenesis of NMO. We evaluated the sensitivity and specificity of NMO-IgG assay for diagnosing NMO patients and differentiating them from MS patients and those with undifferentiated IDD with overlap symptoms.Eligibility of patients with demyelinating disorders was evaluated based on physical examination, laboratory and imaging studies. Thirty four definite NMO patients (disregarding NMO-IgG status), 34 multiple sclerosis (MS) patients with a history of optic neuritis (ON) or myelitis that were matched for age and disease activity and 44 patients with ON or myelitis attacks fulfilling neither criteria of MS or NMO (NMO spectrum) were selected as undifferentiated group. NMO-IgG was measured in the serum of the included patients by cell-based indirect immunofluorescence assay (IFA). NMO antibody was positive in 11 (32.3%), and 4 (9.09%) patients in NMO and undifferentiated groups, but was undetctable in MS patients. NMO antibody was 32% (95%Cl: 19-49%) sensitive in detecting NMO patients. Its specificity in differentiating NMO from MS subjects was 100 % (95% Cl: 90-!00%). NMO antibody was 95% (95% Cl: 0.88-0.98) specific in differentiating NMOs from other demyelinating diseases. Our results showed that although NMO antibody is highly specific for NMO, current method of measuring it with cell-based IFA is not highly sensitive for diagnosing NMO patients.
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February 2015

Nutrition and lung cancer: a case control study in Iran.

BMC Cancer 2014 Nov 21;14:860. Epub 2014 Nov 21.

Lung Transplantation Research Center, National Research and Institute of Tuberculosis and Lung Diseases (NRITLD), Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences, Shaheed Bahonar Ave, Darabad, Tehran 1955841452, Iran.

Background: Despite many prospective and retrospective studies about the association of dietary habit and lung cancer, the topic still remains controversial. So, this study aims to investigate the association of lung cancer with dietary factors.

Method: In this study 242 lung cancer patients and their 484 matched controls on age, sex, and place of residence were enrolled between October 2002 to 2005. Trained physicians interviewed all participants with standardized questionnaires. The middle and upper third consumer groups were compared to the lower third according to the distribution in controls unless the linear trend was significant across exposure groups.

Result: Conditional logistic regression was used to evaluate the association with lung cancer. In a multivariate analysis fruit (Ptrend < 0.0001), vegetable (P = 0.001) and sunflower oil (P = 0.006) remained as protective factors and rice (P = 0.008), bread (Ptrend = 0.04), liver (P = 0.004), butter (Ptrend = 0.04), white cheese (Ptrend < 0.0001), beef (Ptrend = 0.005), vegetable ghee (P < 0.0001) and, animal ghee (P = 0.015) remained as risk factors of lung cancer. Generally, we found positive trend between consumption of beef (P = 0.002), bread (P < 0.0001), and dairy products (P < 0.0001) with lung cancer. In contrast, only fruits were inversely related to lung cancer (P < 0.0001).

Conclusion: It seems that vegetables, fruits, and sunflower oil could be protective factors and bread, rice, beef, liver, dairy products, vegetable ghee, and animal ghee found to be possible risk factors for the development of lung cancer in Iran.
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http://dx.doi.org/10.1186/1471-2407-14-860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4247167PMC
November 2014

Melatonin for prevention of metabolic side-effects of olanzapine in patients with first-episode schizophrenia: randomized double-blind placebo-controlled study.

J Psychiatr Res 2014 Jun 24;53:133-40. Epub 2014 Feb 24.

Department of Psychiatry, Shafa Hospital, Guilan University of Medical Sciences, Rasht, Iran. Electronic address:

Unlabelled: We aimed to determine the efficacy of melatonin 3 mg/day in prevention of olanzapine-induced metabolic side-effects. In a randomized double-blind placebo-controlled study, 48 patients with first-episode schizophrenia who were eligible for olanzapine treatment, were randomly assigned to olanzapine plus either melatonin 3 mg/day or matched placebo for eight weeks. Anthropometric and metabolic parameters as well as psychiatric symptoms using The Positive and Negative Syndrome Scale (PANSS) were assessed at baseline, week 4, and 8. Primary outcome measure was the change from baseline in weight at week 8. Data were analyzed using t-test, Mann-Whitney U test, and mixed-effects model. Thirty-six patients had at least one post-baseline measurement. At week eight, melatonin was associated with significantly less weight gain [mean difference (MD) = 3.2 kg, P = 0.023], increase in waist circumference [MD = 2.83 cm, P = 0.041] and triglyceride concentration [MD = 62 mg/dl, P = 0.090 (nearly significant)] than the placebo. Changes in cholesterol, insulin, and blood sugar concentrations did not differ significantly between the two groups. Patients in the melatonin group experienced significantly more reduction in their PANSS scores [MD = 12.9 points, P = 0.014] than the placebo group. No serious adverse events were reported. To summarize, in patients treated with olanzapine, short-term melatonin treatment attenuates weight gain, abdominal obesity, and hypertriglyceridemia. It might also provide additional benefit for treatment of psychosis. The study was registered in the ClinicalTrials.gov (

Registration Number: NCT01593774).
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http://dx.doi.org/10.1016/j.jpsychires.2014.02.013DOI Listing
June 2014

Trend of blood cholesterol level in Iran: results of four national surveys during 1991-2008.

Acta Med Iran 2013 ;51(9):642-51

Department of Epidemiology and Biostatistics, School of Public Health and Institute of Public Health Research, Tehran University of Medical Sciences, Tehran, Iran.

Trends in cholesterol level of different populations have been investigated in several studies. This study is conducted to determine the trend of cholesterol level of Iranian adults from 1990 to 2007. Data on cholesterol measurements of four national health surveys that have been carried out in Iran used in this study. Cholesterol level of 12728 adults aged 25-64 were measured in 1990-1 survey. Also in 1999, 2005, and 2007 surveys, blood cholesterol level of 18398, 52344 and 19630 have been sampled, respectively. The median of cholesterol were modeled with age for men and women separately for the four surveys using fractional polynomials. Then, trends in the median of cholesterol across these four surveys were studied. The analysis of cholesterol data over four national health surveys showed that the change in males' cholesterol level had a decreasing trend. This decreasing trend was more pronounced in ages younger than 45 years. However, the medians of cholesterol of females during 16 years of four national surveys had a varying trend. It was decreasing in ages younger than 45; but increasing in ages over 45 years. The median of the cholesterol level of males and females in 2005 survey was on average about 10 mg/dl higher in comparison with the other surveys. Our findings showed that the pattern of trend in cholesterol level of Iranian men and women adults have a considerable difference with those of the other developing and developed countries.
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July 2014

Quality and quantity of research publications by Iranian neurosurgeons: Signs of scientific progress over the past decades.

Surg Neurol Int 2013 28;4:38. Epub 2013 Mar 28.

Department of Neurosurgery, Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Background: This is an analysis of papers published by Iranian neurosurgeons while working in Iran until the year 2010.

Methods: We collected bibliometric data and assigned a level of evidence (LOE) for each paper and compared neurosurgical research productivity across three time periods (before 1990, between 1991 and 2000, and after 2000). For further illustration, the annual growth rates of Iranian publications were calculated for all papers published after 1995.

Results: We found a total of 1196 papers by 422 Iranian neurosurgeons. Five authors accounted for 22.9% of the papers. The average number of authors for each published manuscript was 3.48 and increased significantly from 2.0 to 4.0 across the three investigated periods (P < 0.001). 58.9% of Iranian papers were published in local journals only. A total of 74.6% articles were published after 2000, which was a significant increase compared with the decades before (P < 0.001). Original articles and case reports accounted for 63.8% and 31.1% of the publications, respectively. The proportion of case reports decreased while the proportion of original articles increased across the three time periods (P < 0.001). The adjusted growth rate for the total number of publications, original articles, case reports, clinical trials, and randomized clinical trials (RCTs) were 14.4%, 16.6%, 10.7%, 13.46%, and 14.7% per year, respectively. Overall, the four most frequently investigated topics were spine (27.3%), trauma (22.3%), tumor (19.1%), and vascular diseases (13.5%). The mean impact factor for journals publishing these studies and average number of citations for each paper (obtained from web of science) were found to be 1.2 and 5.46, respectively. A partitioning of these publications into assigned categories reflecting the LOE of each paper yielded the following LOE distribution for all assessed publications: Ib: 6.02%, Ic: 0.3%, IIa: 0.2%, IIb: 5.4%, IIc: 0.41%, IIIb: 4.8%, IV: 22.5%, and V: 1.2%. The relative number of publications categorized into higher LOE classes increased over the three investigated periods (P = 0.003). Based on growth curve model, the rate of increase in total numbers of publications following each position change from nonuniversity affiliated neurosurgeon to university affiliated and from university affiliated neurosurgeon to chairman university affiliated neurosurgeon was 81%.

Conclusions: A considerable increase in amount and quality of Iranian papers was observed during the past decade as reflected in a higher number of papers categorized in upper LOE classes.
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http://dx.doi.org/10.4103/2152-7806.109651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3622377PMC
April 2013

Serum cholesterol level nomograms for Iranian population; suggestion for national cut-offs.

Iran J Public Health 2013 1;42(2):164-71. Epub 2013 Feb 1.

Dept. of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Background: High cholesterol levels are associated with increased risk of coronary heart disease and stroke. Understanding the distribution of serum cholesterol levels in each country is valuable index for use in public health planning. This study aimed to construct nomograms of total cholesterol (TC) levels and establish the cut-points specific to Iranian population.

Methods: Data on serum TC levels of 19,630 non-institutionalized individuals aged 25-64 years from third national survey on non-communicable diseases (SuRFNCD) in 2007 were used to construct cholesterol nomograms. We proposed cutoff values for borderline and high TC levels based on rounded 75th and 90th percentiles in three age groups (25-34, 35-44 and 45-64) respectively.

Results: Average yearly increase of TC for males up to the age of 45 and females up to 64 were 1.15 and 1.03 mg/dl, respectively. TC levels were higher in females. In males, cutoff values for "borderline and high" TC levels were 195 and 220 mg/dl in 25-34, 210 and 240 mg/d in 35-44 and 215 and 245 mg/dl in 45-64 years old individuals. In women, these values were 200 and 225 mg/dl in 25-34,215 and 240 mg/dl in 35-44 and 235 and 265 mg/dl in 45-64 years old individuals respectively.

Conclusion: Since TC levels are different in two sexes and change with age, we proposed different cutoffs for sex and age group. We think these cutoffs could be used in national public health planning.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3595653PMC
March 2013

Transient elastography in hepatitis C virus-infected patients with beta-thalassemia for assessment of fibrosis.

Hepatol Res 2013 Dec 12;43(12):1276-83. Epub 2013 Mar 12.

Digestive Diseases Research Institute, Shariati Hospital, Tehran, Iran.

Aim: We sought to evaluate the performance of transient elastography (TE) for the assessment of liver fibrosis in chronic hepatitis C (CHC) patients with beta-thalassemia.

Methods: Seventy-six CHC patients with beta-thalassemia underwent TE, liver biopsy, T2 -weighted magnetic resonance imaging (MRI) for the assessment of liver iron content (LIC) and laboratory evaluation. The accuracy of TE and its correlation with the other variables was assessed.

Results: TE values increased proportional to fibrosis stage (r = 0.404, P < 0.001), but was independent of T2 -weighted MRI-LIC (r = 0.064, P = 0.581). In multivariate analysis, fibrosis stage was still associated with the log-transformed TE score(standardized β = 0.42 for F4 stage of METAVIR, P = 0.001). No correlation was noted between LIC and TE score (standardized β = 0.064, P = 0.512). The area under the receiver operating characteristic curve for prediction of cirrhosis was 80% (95% confidence interval, 59-100%). A cut-off TE score of 11 had a sensitivity of 78% and specificity of 88.1% for diagnosing cirrhosis. The best cut-off values for "TE-FIB-4 cirrhosis score" comprising TE and FIB-4 and "TE-APRI cirrhosis score" combining TE with aspartate aminotransferase-to-platelet ratio index (APRI) both had 87.5% sensitivity and 91.04% specificity for the diagnosis of cirrhosis.

Conclusion: Regardless of LIC, TE alone or when combined with FIB-4 or APRI, is a diagnostic tool with moderate to high accuracy to evaluate liver fibrosis in CHC patients with beta-thalassemia. However, because splenectomy in a proportion of our subjects might have affected the platelet count, the scores utilizing APRI and FIB-4 should be interpreted cautiously.
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http://dx.doi.org/10.1111/hepr.12088DOI Listing
December 2013

Cytokine alterations in bipolar disorder: a meta-analysis of 30 studies.

Biol Psychiatry 2013 Jul 16;74(1):15-25. Epub 2013 Feb 16.

Department of Psychiatry and Psychiatry Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Background: We conducted a meta-analysis of studies comparing cytokine concentrations between patients with bipolar disorder (BD) and healthy control subjects (HCs).

Methods: We searched ISI Web of Science, MEDLINE, BIOSIS Previews, Scopus, Current Contents Connect, and Biological Abstracts for relevant studies. Based on heterogeneity status, we used fixed-effect or restricted maximal likelihood model to perform meta-analysis.

Results: Thirty studies with a total of 2599 participants (1351 BD and 1248 HCs) were eligible for the analysis. Concentrations of interleukin (IL)-4 (p = .008), IL-6 (p = .073), IL-10 (p = .013), soluble IL-2 receptor (sIL-2R; p < .001), sIL-6R (p = .021), tumor necrosis factor (TNF)-α (p = .010), soluble TNF receptor-1 (sTNFR1; p < .001), and IL-1 receptor antagonist (p value in mania < .001 and euthymia = .021) were significantly elevated in patients compared with HCs. Moreover, IL-1β (p = .059), and IL-6 (p = .073) tended to show higher values in patients. Levels of IL-2 (p = .156), interferon (INF)-γ (p = .741), C-C motif ligand 2 (p = .624), and IL-8 (p = .952) did not significantly differ between patients and HCs. Subgroup analysis based on mitogen stimulation status partially or completely resolved heterogeneity for most of the cytokines. Concentrations of IL-2, IL-4, sIL-6R, and INF-γ were unrelated to medication status. Phasic difference was present for TNF-α, sTNFR1, sIL-2R, IL-6, and IL-1RA, whereas it was absent for IL-4 and IL-10.

Conclusions: This meta-analysis provides evidence for significant elevation of proinflammatory, anti-inflammatory, and regulatory cytokines in BD.
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http://dx.doi.org/10.1016/j.biopsych.2013.01.007DOI Listing
July 2013

Treatment with pioglitazone is associated with decreased preprandial ghrelin levels: a randomized clinical trial.

Peptides 2013 Feb 28;40:89-92. Epub 2012 Dec 28.

Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, Tehran University of Medical Sciences, Tehran, Iran.

The effects of metformin and pioglitazone on ghrelin, a physiologic regulator of appetite and food intake, have not been clearly established. In a randomized clinical trial, we randomly assigned 60 type 2 diabetic patients to either metformin (Group A; n=30) or pioglitazone (Group B; n=30) treatment groups. The groups were similar in their baseline characteristics. A standard fasting 75 g oral glucose tolerance test was performed at time zero before starting metformin or pioglitazone, and 3 months later. After 3 months of treatment, pioglitazone, but not metformin, was significantly associated with weight gain. Both groups experienced a significant reduction in fasting plasma glucose (p<0.01), hemoglobin A1c (p<0.01 in Group A and p<0.05 in Group B), and insulin resistance (p<0.01). The effect of metformin on preprandial ghrelin and its response to glucose challenge was not significant, while the pioglitazone group had a significant reduction in preprandial ghrelin levels after treatment (p<0.05). The effect of pioglitazone on ghrelin was independent of changes in body weight, body mass index, glucose control, insulin resistance, and plasma insulin. In conclusion, treatment with pioglitazone is associated with a decrease in preprandial ghrelin levels and therefore, the weight gain and increased food intake related to pioglitazone use cannot be explained by its effects on ghrelin. The effect of pioglitazone on ghrelin is independent of changes in body weight, body mass index, plasma insulin, insulin resistance, or glucose control.
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http://dx.doi.org/10.1016/j.peptides.2012.12.020DOI Listing
February 2013

Ondansetron in patients with tinnitus: randomized double-blind placebo-controlled study.

Eur Arch Otorhinolaryngol 2013 May 22;270(5):1635-41. Epub 2012 Sep 22.

Otorhinolaryngology Research Center, Tehran University of Medical Sciences, Tehran, Iran.

The aim of this study was to assess the effect of ondansetron on symptoms of patients with subjective tinnitus accompanied by sensorineural hearing loss or normal hearing. Sixty patients with a chief complaint of tinnitus (with duration of more than 3 months) were equally randomized to ondansetron or placebo for 4 weeks. The dose of ondansetron was gradually increased from 4 mg/day (one tablet) to 16 mg/day (4 tablets) during 12 days and then continued up to 4 weeks. The exact number of tablets was prescribed in the placebo group. Patients underwent audiologic examinations and filled questionnaires at baseline and after 4 weeks of treatment. Our primary outcomes were changes in Tinnitus Handicap Inventory questionnaire (THI), Tinnitus Severity Index (TSI) and visual analog scale (VAS) scores. Our secondary outcomes were the changes in depression and anxiety based on Hospital Anxiety and Depression (HADS) questionnaire, side effects, tinnitus loudness matching, tinnitus pitch matching, pure tone audiometry and speech recognition threshold (SRT). In the ondansetron and placebo groups, 27 and 26 patients completed the study, respectively. The changes in VAS (P = 0.934), THI (P = 0.776), anxiety (P = 0.313) and depression (P = 0.163) scores were not different between the groups. TSI score decreased significantly in the ondansetron compared with the placebo group (P = 0.004). Changes in tinnitus loudness matching (P = 0.75) and pitch matching (P = 0.56) did not differ between the two groups. Ondansetron, but not placebo, decreased the SRT threshold (right, P < 0.001; left, P = 0.043) and mean PTA (right, P = 0.006; left, P < 0.001). In conclusion, ondansetron reduces the severity of tinnitus hypothetically through cochlear amplification.
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http://dx.doi.org/10.1007/s00405-012-2179-0DOI Listing
May 2013

Effect of pirfenidone on pulmonary fibrosis due to paraquat poisoning in rats.

Clin Toxicol (Phila) 2012 Sep;50(8):754-8

Pulmonary and Critical Care Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Background: This study investigated the effectiveness of pirfenidone compared with antioxidants, in the prevention of pulmonary fibrosis and increasing the survival in acutely paraquat poisoned rats.

Methods: Five groups of ten rats were included in this study. Three groups were poisoned with intraperitoneal injection of 15 mg/kg paraquat. Among these poisoned groups, one group was treated with vitamin C (500 mg/kg, intraperitoneal), vitamin E (200 mg/kg, intraperitoneal) and N-acetylcysteine (250 mg/kg, intravenous); two others were treated with either normal saline or pirfenidone (200 mg/kg, intravenous); two groups were not poisoned and received normal saline or pirfenidone (200 mg/kg, intravenous). All injections except paraquat were repeated in four consecutive days. On the 15th day of study a semi-quantitative determination of lung fibrosis was done using Ashcroft staging criteria on the lung sections.

Results: Pirfenidone decreased paraquat induced lung fibrosis (p < 0.001) while antioxidants did not decrease the lung fibrosis (p = 0.413). Life expectancy decreased in paraquat + normal saline (11 days, 95% CI 7.94-14.05) and paraquat + antioxidant (11 days, 95% CI 7.77-14.23) groups. The increase in the survival of rats in paraquat/pirfenidone group was insignificant (13.4 days, 95% CI 11.13-15.67).

Conclusion: This study showed that pirfenidone is able to decrease pulmonary fibrosis following paraquat poisoning in a rat model.
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http://dx.doi.org/10.3109/15563650.2012.718783DOI Listing
September 2012

Predictors of mental and physical health in non-cirrhotic patients with viral hepatitis: a case control study.

J Psychosom Res 2012 Sep 16;73(3):218-24. Epub 2012 Jul 16.

Digestive Disease Research Institute (DDRI), Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Objective: To identify independent predictors of mental and physical health in patients with viral hepatitis.

Methods: Hepatitis C (HCV) and hepatitis B (HBV) infected patients, and community control subjects with equal age and sex distribution were recruited. All subjects filled in personal characteristics questionnaire, Hospital Anxiety and Depression Scale (HADS), Iowa Fatigue Scale (IFS), and Medical Outcomes Survey Short Form-12 (SF-12). All patients had measurement of routine laboratory values, and some had recent liver biopsy. Regression analyses were used to identify predictors of physical and mental health.

Results: One hundred eighty nine subjects (162 males, 27 females, for each group N=63) with mean (±SD) age of 39±11years were included. Anxiety and depression were important predictors of SF-12 (and its subscales MCS and PCS) and IFS scores, whereas IFS scores independently predicted HADS, PCS, MCS, and SF-12 scores. After controlling for confounders, HCV infection was independently associated with impairment of physical health. Moreover, creatinine showed an inverse strong relation with fatigue. Genotype 3a of HCV was independently associated with depressed and anxious states, whereas higher inflammation grade was significantly related to depression. Marital status, non-psychiatric comorbidities, and history of alcohol abuse also predicted health scores in the patients. Adjusted R(2)s for linear models were 0.571 to 0.709, whereas areas under the receiver operating characteristic (ROC) curve for logistic models were 0.90 to 0.93.

Conclusion: In viral hepatitis patients, besides mental and medical comorbidities, marital status, and alcohol abuse, HCV infection itself is associated with impaired physical and possibly mental health.
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http://dx.doi.org/10.1016/j.jpsychores.2012.06.006DOI Listing
September 2012
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