Bio

Bio


Vafi Salmasi, MD, is a specialist in pain medicine with clinical foci in neuromodulation, neuropathic pain; complex regional pain syndrome (CRPS); radiculopathy; spinal stenosis; and postherpetic neuralgia. He received his medical degree from Tehran University, Iran, and completed his residency in anesthesiology at Cleveland Clinic. He then completed his fellowship in pain medicine at Stanford University. He is board certified in both Anesthesiology and Pain Medicine by the American Board of Anesthesiology. Dr. Salmasi is currently a Clinical Instructor of Anesthesiology and Pain Medicine at Stanford University.

Clinical Focus


  • Pain Medicine
  • Pain Management
  • Neuromodulation
  • Spinal Cord Stimulation
  • Neuropathic Pain
  • Back Pain
  • Post-Laminectomy Syndrome
  • CRPS
  • Postherpetic Neuralgia
  • Radiculopathy
  • Spinal Stenosis
  • Perioperative Pain Management

Academic Appointments


  • Instructor, Anesthesiology, Perioperative and Pain Medicine

Honors & Awards


  • Recipient of Michael J. deUngria M.D. Residency Award, Cleveland Clinic Anesthesiology Residency Program (2016)
  • Second place winner in Residents? Research Essay Contest, American Society of Anesthesiologists Annual Meeting (2016)

Professional Education


  • Master's Degree, Stanford University School of Medicine, Epidemiology and Clinical Research (2019)
  • Fellowship: Stanford University Pain Management Fellowship (2017) CA
  • Board Certification: American Board of Anesthesiology, Pain Management (2017)
  • Board Certification: American Board of Anesthesiology, Anesthesia (2017)
  • Medical Education: Tehran University of Medical Sciences (2004) Iran
  • Residency: Cleveland Clinic Foundation (2016) OH
  • Internship: Cleveland Clinic Foundation (2012) OH

Research & Scholarship

Clinical Trials


  • Comparing Effectiveness of Duloxetine and Desipramine in Patients With Chronic Pain: A Pragmatic Trial Using Point of Care Randomization Recruiting

    Over 100 million Americans suffer from chronic pain resulting in annual cost of roughly $635 billion. Limited treatments are available for this widespread disease. The data supporting these treatments lack generalizability to patients with more serious medical and psychological comorbidities who are often excluded from explanatory efficacy trials. Our work aims to integrate randomized comparative effectiveness research with patient care. The investigators will randomize the patients and collect data using an open-source learning healthcare system already in use in our department to monitor patients' progress: Collaborative Health Outcomes Information Registry (CHOIR). Collaborative Health Outcomes Information Registry uses the National Institute of Health Patient Reported Outcomes Measurement Information System item banks for comparative metrics through computer adaptive testing. The investigators will leverage the advantage of this novel system to compare effectiveness of duloxetine and desipramine in decreasing pain in patients with chronic pain. The investigators will also compare adherence of patients to these two commonly used medications over a period of six months. This will evaluate feasibility of integrating randomized comparative effectiveness research with patient care in subspecialty clinics. Collaborative Health Outcomes Information Registry can then be applied for numerous future trials to advance our knowledge in perioperative and pain medicine.

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  • Comparing Long-term Effectiveness of High Frequency and Burst Spinal Cord Stimulation Not Recruiting

    Over 100 million Americans suffer from chronic pain resulting in annual cost of roughly $635 billion. Limited treatments are available for this widespread disease. The data supporting these treatments lack generalizability to patients with more serious medical and psychological comorbidities who are often excluded from explanatory efficacy trials. This study aims to integrate randomized comparative effectiveness research with patient care. The investigators will randomize the patients and collect data using an open-source learning healthcare system already in use in the department to monitor patients' progress: Collaborative Health Outcomes Information Registry (CHOIR). CHOIR uses the National Institute of Health Patient Reported Outcomes Measurement Information System item banks for comparative metrics through computer adaptive testing. The investigators will leverage the advantage of this novel system to compare effectiveness of high frequency and burst spinal cord stimulation in improving pain and function in patients with chronic back and/or leg pain. Spinal cord stimulation is an effective treatment for chronic pain resulting in >50% pain relief in about half of the patients. Novel waveforms for spinal cord stimulation - high frequency and burst - increased the efficacy of this treatment even further. However, there is lack of data guiding decision making of the clinicians in choosing the best waveform in treating the patients with chronic pain. The proposed study will provide the clinicians with this evidence. Currently, data about safety and efficacy of these two novel waveforms is available for up to 24 months. The proposed research will provide data about effectiveness of these two modalities for at least 36 months. Moreover, this study will evaluate feasibility of integrating randomized comparative effectiveness research with patient care in Stanford Pain Management subspecialty clinic. CHOIR can then be applied for numerous future trials to advance knowledge in perioperative and pain medicine.

    Stanford is currently not accepting patients for this trial. For more information, please contact Vafi Salmasi, MD., 650-725-0246.

    View full details

Teaching

Graduate and Fellowship Programs


  • Pain Management (Fellowship Program)

Publications

All Publications


  • Outcomes of Sympathetic Blocks in the Management of Complex Regional Pain Syndrome: A Retrospective Cohort Study. Anesthesiology Cheng, J., Salmasi, V., You, J., Grille, M., Yang, D., Mascha, E. J., Cheng, O. T., Zhao, F., Rosenquist, R. W. 2019

    Abstract

    Sympathetic blocks are used in the diagnosis and treatment planning of patients with complex regional pain syndromeIt is unclear whether the response to sympathetic blocks is associated with spinal cord stimulation trial success WHAT THIS ARTICLE TELLS US THAT IS NEW: In patients with complex regional pain syndrome, skin temperature change is not associated with sympathetic block pain reductionThe short- and long-term effects of sympathetic blocks are not associated with spinal cord stimulation outcomes BACKGROUND:: Sympathetic dysfunction may be present in complex regional pain syndrome, and sympathetic blocks are routinely performed in practice. To investigate the therapeutic and predictive values of sympathetic blocks, the authors test the hypotheses that sympathetic blocks provide analgesic effects that may be associated with the temperature differences between the two extremities before and after the blocks and that the effects of sympathetic blocks may predict the success (defined as achieving more than 50% pain reduction) of spinal cord stimulation trials.The authors performed a retrospective study of 318 patients who underwent sympathetic blocks in a major academic center (2009 to 2016) to assess the association between pain reduction and preprocedure temperature difference between the involved and contralateral limbs. The primary outcome was pain improvement by more than 50%, and the secondary outcome was duration of more than 50% pain reduction per patient report. The authors assessed the association between pain reduction and the success rate of spinal cord stimulation trials.Among the 318 patients, 255 were diagnosed with complex regional pain syndrome and others with various sympathetically related disorders. Successful pain reduction (more than 50%) was observed in 155 patients with complex regional pain syndrome (155 of 255, 61%). The majority of patients (132 of 155, 85%) experienced more than 50% pain relief for 1 to 4 weeks or longer. The degree and duration of pain relief were not associated with preprocedure temperature parameters with estimated odds ratio of 1.03 (97.5% CI, 0.95-1.11) or 1.01 (97.5% CI, 0.96-1.06) for one degree decrease (P = 0.459 or 0.809). There was no difference in the success rate of spinal cord stimulation trials between patients with or without more than 50% pain relief after sympathetic blocks (35 of 40, 88% vs. 26 of 29, 90%, P > 0.990).The authors conclude that sympathetic blocks may be therapeutic in patients with complex regional pain syndrome regardless of preprocedure limb temperatures. The effects of sympathetic blocks do not predict the success of spinal cord stimulation.

    View details for DOI 10.1097/ALN.0000000000002899

    View details for PubMedID 31365367

  • Genomic analysis identifies frequent deletions of Dystrophin in olfactory neuroblastoma NATURE COMMUNICATIONS Gallia, G. L., Zhang, M., Ning, Y., Haffner, M. C., Batista, D., Binder, Z. A., Bishop, J. A., Hann, C. L., Hruban, R. H., Ishii, M., Klein, A. P., Reh, D. D., Rooper, L. M., Salmasi, V., Tamargo, R. J., Wang, Q., Williamson, T., Zhao, T., Zou, Y., Meeker, A. K., Agrawal, N., Vogelstein, B., Kinzler, K. W., Papadopoulos, N., Bettegowda, C. 2018; 9
  • Genomic analysis identifies frequent deletions of Dystrophin in olfactory neuroblastoma. Nature communications Gallia, G. L., Zhang, M., Ning, Y., Haffner, M. C., Batista, D., Binder, Z. A., Bishop, J. A., Hann, C. L., Hruban, R. H., Ishii, M., Klein, A. P., Reh, D. D., Rooper, L. M., Salmasi, V., Tamargo, R. J., Wang, Q., Williamson, T., Zhao, T., Zou, Y., Meeker, A. K., Agrawal, N., Vogelstein, B., Kinzler, K. W., Papadopoulos, N., Bettegowda, C. 2018; 9 (1): 5410

    Abstract

    Olfactory neuroblastoma (ONB) is a rare malignant neoplasm arising in the upper portion of the sinonasal cavity. To better understand the genetic bases for ONB, here we perform whole exome and whole genome sequencing as well as single nucleotide polymorphism array analyses in a series of ONB patient samples. Deletions involving the dystrophin (DMD) locus are found in 12 of 14 (86%) tumors. Interestingly, one of the remaining tumors has a deletion in LAMA2, bringing the number of ONBs with deletions of genes involved in the development of muscular dystrophies to 13 or 93%. This high prevalence implicates an unexpected functional role for genes causing hereditary muscular dystrophies in ONB.

    View details for PubMedID 30575736

  • Relationship between Intraoperative Hypotension, Defined by Either Reduction from Baseline or Absolute Thresholds, and Acute Kidney and Myocardial Injury after Noncardiac Surgery: A Retrospective Cohort Analysis. Anesthesiology Salmasi, V., Maheshwari, K., Yang, D., Mascha, E. J., Singh, A., Sessler, D. I., Kurz, A. 2016: -?

    Abstract

    How best to characterize intraoperative hypotension remains unclear. Thus, the authors assessed the relationship between myocardial and kidney injury and intraoperative absolute (mean arterial pressure [MAP]) and relative (reduction from preoperative pressure) MAP thresholds.The authors characterized hypotension by the lowest MAP below various absolute and relative thresholds for cumulative 1, 3, 5, or 10?min and also time-weighted average below various absolute or relative MAP thresholds. The authors modeled each relationship using logistic regression. The authors further evaluated whether the relationships between intraoperative hypotension and either myocardial or kidney injury depended on baseline MAP. Finally, the authors compared the strength of associations between absolute and relative thresholds on myocardial and kidney injury using C statistics.MAP below absolute thresholds of 65 mmHg or relative thresholds of 20% were progressively related to both myocardial and kidney injury. At any given threshold, prolonged exposure was associated with increased odds. There were no clinically important interactions between preoperative blood pressures and the relationship between hypotension and myocardial or kidney injury at intraoperative mean arterial blood pressures less than 65 mmHg. Absolute and relative thresholds had comparable ability to discriminate patients with myocardial or kidney injury from those without.The associations based on relative thresholds were no stronger than those based on absolute thresholds. Furthermore, there was no clinically important interaction with preoperative pressure. Anesthetic management can thus be based on intraoperative pressures without regard to preoperative pressure.

    View details for PubMedID 27792044

  • Clonidine Does Not Reduce Pain or Opioid Consumption After Noncardiac Surgery. Anesthesia and analgesia Turan, A., Babazade, R., Kurz, A., Devereaux, P. J., Zimmerman, N. M., Hutcherson, M. T., Naylor, A. J., Ali Sakr Esa, W., Parlow, J., Gilron, I., Honar, H., Salmasi, V., Sessler, D. I. 2016; 123 (3): 749-757

    Abstract

    Clonidine is an ?2-adrenoceptor agonist, which has analgesic properties. However, the analgesic efficacy of perioperative clonidine remains unclear. We, therefore, tested the hypothesis that clonidine reduces both pain scores and cumulative opioid consumption during the initial 72 hours after noncardiac surgery.Six hundred twenty-four patients undergoing elective noncardiac surgery under general and spinal anesthesia were included in this substudy of the PeriOperative ISchemia Evaluation-2 trial. Patients were randomly assigned to 0.2 mg oral clonidine or placebo 2 to 4 hours before surgery, followed by 0.2 mg/d transdermal clonidine patch or placebo patch, which was maintained until 72 hours after surgery. Postoperative pain scores and opioid consumption were assessed for 72 hours after surgery.Clonidine had no effect on opioid consumption compared with placebo, with an estimated ratio of means of 0.98 (95% confidence interval, 0.70-1.38); P = 0.92. Median (Q1, Q3) opioid consumption was 63 (30, 154) mg morphine equivalents in the clonidine group, which was similar to 60 (30, 128) mg morphine equivalents in the placebo group. Furthermore, there was no significant effect on pain scores, with an estimated difference in means of 0.12 (95% confidence interval, -0.02 to 0.26); 11-point scale; P = 0.10. Mean pain scores per patient were 3.6 1.8 for clonidine patients and 3.6 1.8 for placebo patients.Clonidine does not reduce opioid consumption or pain scores in patients recovering from noncardiac surgery.

    View details for DOI 10.1213/ANE.0000000000001356

    View details for PubMedID 27537762

  • Establishment and Biological Characterization of a Panel of Glioblastoma Multiforme (GBM) and GBM Variant Oncosphere Cell Lines PLOS ONE Binder, Z. A., Wilson, K. M., Salmasi, V., Orr, B. A., Eberhart, C. G., Siu, I., Lim, M., Weingart, J. D., Quinones-Hinojosa, A., Bettegowda, C., Kassam, A. B., Olivi, A., Brem, H., Riggins, G. J., Gallia, G. L. 2016; 11 (3)

    Abstract

    Human tumor cell lines form the basis of the majority of present day laboratory cancer research. These models are vital to studying the molecular biology of tumors and preclinical testing of new therapies. When compared to traditional adherent cell lines, suspension cell lines recapitulate the genetic profiles and histologic features of glioblastoma multiforme (GBM) with higher fidelity. Using a modified neural stem cell culture technique, here we report the characterization of GBM cell lines including GBM variants.Tumor tissue samples were obtained intra-operatively and cultured in neural stem cell conditions containing growth factors. Tumor lines were characterized in vitro using differentiation assays followed by immunostaining for lineage-specific markers. In vivo tumor formation was assayed by orthotopic injection in nude mice. Genetic uniqueness was confirmed via short tandem repeat (STR) DNA profiling.Thirteen oncosphere lines derived from GBM and GBM variants, including a GBM with PNET features and a GBM with oligodendroglioma component, were established. All unique lines showed distinct genetic profiles by STR profiling. The lines assayed demonstrated a range of in vitro growth rates. Multipotency was confirmed using in vitro differentiation. Tumor formation demonstrated histologic features consistent with high grade gliomas, including invasion, necrosis, abnormal vascularization, and high mitotic rate. Xenografts derived from the GBM variants maintained histopathological features of the primary tumors.We have generated and characterized GBM suspension lines derived from patients with GBMs and GBM variants. These oncosphere cell lines will expand the resources available for preclinical study.

    View details for DOI 10.1371/journal.pone.0150271

    View details for Web of Science ID 000373116500004

    View details for PubMedID 27028405

  • Identification of location of nerve catheters using pumping maneuver and M-Mode-a novel technique JOURNAL OF CLINICAL ANESTHESIA Elsharkawy, H., Salmasi, V., Abd-Elsayed, A., Turan, A. 2015; 27 (4): 325-330

    Abstract

    Optimum positioning of the nerve catheter is crucial for a successful nerve block. We present a novel technique for confirmation of catheter position.We are describing a novel technique for localization of the shaft and tip of the peripheral nerve catheter. After introduction of the catheter 3 to 5 cm beyond the needle tip and removal of the needle, the guide wire was reintroduced and was moved inward and outward rapidly. This movement produced the color Doppler effect along the track of the catheter and the catheter tip that helped us verify the proper positioning of the catheter.We used our technique in a cadaveric study for bilateral supraclavicular brachial plexus block, followed by a series of 5 patients undergoing femoral, sciatic (anterior approach), popliteal (2 patients), and brachial plexus blocks. Catheters were also identified on M-Mode sonography during pumping maneuver and during the injection of medications.Pumping maneuver and M-Mode can be additional tools in the array of modalities applied to verify proper positioning of a nerve catheter.

    View details for DOI 10.1016/j.jclinane.2015.03.003

    View details for Web of Science ID 000355896400008

    View details for PubMedID 25837495

  • Intraoperative hypertensive crisis due to a catecholamine-secreting esthesioneuroblastoma HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Salmasi, V., Schiavi, A., Binder, Z. A., Ruzevick, J., Orr, B. A., Burger, P. C., Ball, D. W., Blitz, A. M., Koch, W. M., Ishii, M., Gallia, G. L. 2015; 37 (6): E74-E80

    Abstract

    Although uncommon, esthesioneuroblastomas may produce clinically significant amounts of catecholamines.We report a patient with a catecholamine-secreting esthesioneuroblastoma who developed an intraoperative hypertensive crisis.A patient with a history of hypertension was referred to our skull base center for management of a residual esthesioneuroblastoma. A staged endonasal endoscopic approach was planned. At the conclusion of the first stage, a hypertensive crisis occurred. Workup revealed elevated levels of serum and urinary catecholamines. The patient was treated with alpha adrenoceptor blockade before the second stage. Serum catecholamine levels after this second stage were normal. On immunohistochemical analysis, the tumor cells were found to be positive for tyrosine hydroxylase, the rate limiting enzyme in catecholamine synthesis, and achaete-scute homologue 1, a transcription factor essential in the development of olfactory and sympathetic neurons.Catecholamine production should be considered in the differential of unexpected extreme hypertension during surgical resection of esthesioneuroblastoma.

    View details for DOI 10.1002/hed.23907

    View details for Web of Science ID 000355012000002

    View details for PubMedID 25352487

  • Intraoperative Core Temperature Patterns, Transfusion Requirement, and Hospital Duration in Patients Warmed with Forced Air ANESTHESIOLOGY Sun, Z., Honar, H., Sessler, D. I., Dalton, J. E., Yang, D., Panjasawatwong, K., Deroee, A. F., Salmasi, V., Saager, L., Kurz, A. 2015; 122 (2): 276-285

    Abstract

    Core temperature patterns in patients warmed with forced air remain poorly characterized. Also unknown is the extent to which transient and mild intraoperative hypothermia contributes to adverse outcomes in broad populations.We evaluated esophageal (core) temperatures in 58,814 adults having surgery lasting >60 min who were warmed with forced air. Independent associations between hypothermic exposure and transfusion requirement and duration of hospitalization were evaluated.In every percentile subgroup, core temperature decreased during the first hour and subsequently increased. The mean lowest core temperature during the first hour was 35.7 0.6C. Sixty-four percent of the patients reached a core temperature threshold of <36C 45 min after induction; 29% reached a core temperature threshold of <35.5C. Nearly half the patients had continuous core temperatures <36C for more than an hour, and 20% of the patients were <35.5C for more than an hour. Twenty percent of patients had continuous core temperatures <36C for more than 2 h, and 8% of the patients were below 35.5C for more than 2 h. Hypothermia was independently associated with both transfusions and duration of hospitalization, although the prolongation of hospitalization was small.Even in actively warmed patients, hypothermia is routine during the first hour of anesthesia. Thereafter, average core temperatures progressively increase. Nonetheless, intraoperative hypothermia was common, and often prolonged. Hypothermia was associated with increased transfusion requirement, which is consistent with numerous randomized trials.

    View details for DOI 10.1097/ALN.0000000000000551

    View details for Web of Science ID 000351734900007

    View details for PubMedID 25603202

  • Perioperative aspirin and clonidine and risk of acute kidney injury: a randomized clinical trial. JAMA Garg, A. X., Kurz, A., Sessler, D. I., Cuerden, M., Robinson, A., Mrkobrada, M., Parikh, C. R., Mizera, R., Jones, P. M., Tiboni, M., Font, A., Cegarra, V., Gomez, M. F., Meyhoff, C. S., VanHelder, T., Chan, M. T., Torres, D., Parlow, J., Clanchet, M. d., Amir, M., Bidgoli, S. J., Pasin, L., Martinsen, K., Malaga, G., Myles, P., Acedillo, R., Roshanov, P. S., Walsh, M., Dresser, G., Kumar, P., Fleischmann, E., Villar, J. C., Painter, T., Biccard, B., Bergese, S., Srinathan, S., Cata, J. P., Chan, V., Mehra, B., Wijeysundera, D. N., Leslie, K., Forget, P., Whitlock, R., Yusuf, S., Devereaux, P. J. 2014; 312 (21): 2254-2264

    Abstract

    Acute kidney injury, a common complication of surgery, is associated with poor outcomes and high health care costs. Some studies suggest aspirin or clonidine administered during the perioperative period reduces the risk of acute kidney injury; however, these effects are uncertain and each intervention has the potential for harm.To determine whether aspirin compared with placebo, and clonidine compared with placebo, alters the risk of perioperative acute kidney injury.A 2??2 factorial randomized, blinded, clinical trial of 6905 patients undergoing noncardiac surgery from 88 centers in 22 countries with consecutive patients enrolled between January 2011 and December 2013.Patients were assigned to take aspirin (200 mg) or placebo 2 to 4 hours before surgery and then aspirin (100 mg) or placebo daily up to 30 days after surgery, and were assigned to take oral clonidine (0.2 mg) or placebo 2 to 4 hours before surgery, and then a transdermal clonidine patch (which provided clonidine at 0.2 mg/d) or placebo patch that remained until 72 hours after surgery.Acute kidney injury was primarily defined as an increase in serum creatinine concentration from the preoperative concentration by either an increase of 0.3 mg/dL or greater (?26.5 ?mol/L) within 48 hours of surgery or an increase of 50% or greater within 7 days of surgery.Aspirin (n?=?3443) vs placebo (n?=?3462) did not alter the risk of acute kidney injury (13.4% vs 12.3%, respectively; adjusted relative risk, 1.10; 95% CI, 0.96-1.25). Clonidine (n?=?3453) vs placebo (n?=?3452) did not alter the risk of acute kidney injury (13.0% vs 12.7%, respectively; adjusted relative risk, 1.03; 95% CI, 0.90-1.18). Aspirin increased the risk of major bleeding. In a post hoc analysis, major bleeding was associated with a greater risk of subsequent acute kidney injury (23.3% when bleeding was present vs 12.3% when bleeding was absent; adjusted hazard ratio, 2.20; 95% CI, 1.72-2.83). Similarly, clonidine increased the risk of clinically important hypotension. In a post hoc analysis, clinically important hypotension was associated with a greater risk of subsequent acute kidney injury (14.3% when hypotension was present vs 11.8% when hypotension was absent; adjusted hazard ratio, 1.34; 95% CI, 1.14-1.58).Among patients undergoing major noncardiac surgery, neither aspirin nor clonidine administered perioperatively reduced the risk of acute kidney injury.clinicaltrials.gov Identifier: NCT01082874.

    View details for DOI 10.1001/jama.2014.15284

    View details for PubMedID 25399007

  • Clonidine in Patients Undergoing Noncardiac Surgery NEW ENGLAND JOURNAL OF MEDICINE Devereaux, P. J., Sessler, D. I., Leslie, K., Kurz, A., Mrkobrada, M., Alonso-Coello, P., Villar, J. C., Sigamani, A., Biccard, B. M., Meyhoff, C. S., Parlow, J. L., Guyatt, G., Robinson, A., Garg, A. X., Rodseth, R. N., Botto, F., Buse, G. L., Xavier, D., Chan, M. T., TIBONI, M., Cook, D., Kumar, P. A., Forget, P., Malaga, G., Fleischmann, E., Amir, M., Eikelboom, J., MIZERA, R., Torres, D., Wang, C. Y., VanHelder, T., Paniagua, P., Berwanger, O., Srinathan, S., Graham, M., Pasin, L., Le Manach, Y., Gao, P., Pogue, J., Whitlock, R., Lamy, A., Kearon, C., Chow, C., Pettit, S., Chrolavicius, S., Yusuf, S. 2014; 370 (16): 1504-1513

    Abstract

    Marked activation of the sympathetic nervous system occurs during and after noncardiac surgery. Low-dose clonidine, which blunts central sympathetic outflow, may prevent perioperative myocardial infarction and death without inducing hemodynamic instability.We performed a blinded, randomized trial with a 2-by-2 factorial design to allow separate evaluation of low-dose clonidine versus placebo and low-dose aspirin versus placebo in patients with, or at risk for, atherosclerotic disease who were undergoing noncardiac surgery. A total of 10,010 patients at 135 centers in 23 countries were enrolled. For the comparison of clonidine with placebo, patients were randomly assigned to receive clonidine (0.2 mg per day) or placebo just before surgery, with the study drug continued until 72 hours after surgery. The primary outcome was a composite of death or nonfatal myocardial infarction at 30 days.Clonidine, as compared with placebo, did not reduce the number of primary-outcome events (367 and 339, respectively; hazard ratio with clonidine, 1.08; 95% confidence interval [CI], 0.93 to 1.26; P=0.29). Myocardial infarction occurred in 329 patients (6.6%) assigned to clonidine and in 295 patients (5.9%) assigned to placebo (hazard ratio, 1.11; 95% CI, 0.95 to 1.30; P=0.18). Significantly more patients in the clonidine group than in the placebo group had clinically important hypotension (2385 patients [47.6%] vs. 1854 patients [37.1%]; hazard ratio 1.32; 95% CI, 1.24 to 1.40; P<0.001). Clonidine, as compared with placebo, was associated with an increased rate of nonfatal cardiac arrest (0.3% [16 patients] vs. 0.1% [5 patients]; hazard ratio, 3.20; 95% CI, 1.17 to 8.73; P=0.02).Administration of low-dose clonidine in patients undergoing noncardiac surgery did not reduce the rate of the composite outcome of death or nonfatal myocardial infarction; it did, however, increase the risk of clinically important hypotension and nonfatal cardiac arrest. (Funded by the Canadian Institutes of Health Research and others; POISE-2 ClinicalTrials.gov number, NCT01082874.).

    View details for DOI 10.1056/NEJMoa1401106

    View details for Web of Science ID 000334601600007

    View details for PubMedID 24679061

  • Aspirin in Patients Undergoing Noncardiac Surgery NEW ENGLAND JOURNAL OF MEDICINE Devereaux, P. J., Mrkobrada, M., Sessler, D. I., Leslie, K., Alonso-Coello, P., Kurz, A., Villar, J. C., Sigamani, A., Biccard, B. M., Meyhoff, C. S., Parlow, J. L., Guyatt, G., Robinson, A., Garg, A. X., Rodseth, R. N., Botto, F., Buse, G. L., Xavier, D., Chan, M. T., TIBONI, M., Cook, D., Kumar, P. A., Forget, P., Malaga, G., Fleischmann, E., Amir, M., Eikelboom, J., MIZERA, R., Torres, D., Wang, C. Y., VanHelder, T., Paniagua, P., Berwanger, O., Srinathan, S., Graham, M., Pasin, L., Le Manach, Y., Gao, P., Pogue, J., Whitlock, R., Lamy, A., Kearon, C., BAIGENT, C., Chow, C., Pettit, S., Chrolavicius, S., Yusuf, S. 2014; 370 (16): 1494-1503

    Abstract

    There is substantial variability in the perioperative administration of aspirin in patients undergoing noncardiac surgery, both among patients who are already on an aspirin regimen and among those who are not.Using a 2-by-2 factorial trial design, we randomly assigned 10,010 patients who were preparing to undergo noncardiac surgery and were at risk for vascular complications to receive aspirin or placebo and clonidine or placebo. The results of the aspirin trial are reported here. The patients were stratified according to whether they had not been taking aspirin before the study (initiation stratum, with 5628 patients) or they were already on an aspirin regimen (continuation stratum, with 4382 patients). Patients started taking aspirin (at a dose of 200 mg) or placebo just before surgery and continued it daily (at a dose of 100 mg) for 30 days in the initiation stratum and for 7 days in the continuation stratum, after which patients resumed their regular aspirin regimen. The primary outcome was a composite of death or nonfatal myocardial infarction at 30 days.The primary outcome occurred in 351 of 4998 patients (7.0%) in the aspirin group and in 355 of 5012 patients (7.1%) in the placebo group (hazard ratio in the aspirin group, 0.99; 95% confidence interval [CI], 0.86 to 1.15; P=0.92). Major bleeding was more common in the aspirin group than in the placebo group (230 patients [4.6%] vs. 188 patients [3.8%]; hazard ratio, 1.23; 95% CI, 1.01, to 1.49; P=0.04). The primary and secondary outcome results were similar in the two aspirin strata.Administration of aspirin before surgery and throughout the early postsurgical period had no significant effect on the rate of a composite of death or nonfatal myocardial infarction but increased the risk of major bleeding. (Funded by the Canadian Institutes of Health Research and others; POISE-2 ClinicalTrials.gov number, NCT01082874.).

    View details for DOI 10.1056/NEJMoa1401105

    View details for Web of Science ID 000334601600006

    View details for PubMedID 24679062

  • NY-ESO-1 Expression in Meningioma Suggests a Rationale for New Immunotherapeutic Approaches CANCER IMMUNOLOGY RESEARCH Baia, G. S., Caballero, O. L., Ho, J. S., Zhao, Q., Cohen, T., Binder, Z. A., Salmasi, V., Gallia, G. L., Quinones-Hinojosa, A., Olivi, A., Brem, H., Burger, P., Strausberg, R. L., Simpson, A. J., Eberhart, C. G., Riggins, G. J. 2013; 1 (5): 296-302

    Abstract

    Meningiomas are the most common primary intracranial tumors. Surgical resection remains the treatment of choice for these tumors. However, a significant number of tumors are not surgically accessible, recur, or become malignant, necessitating the repetition of surgery and sometimes radiation. Chemotherapy is rarely used and is generally not recognized as an effective treatment. Cancer/testis (CT) genes represent a unique class of genes, which are expressed by germ cells, normally silenced in somatic cells, but activated in various cancers. CT proteins can elicit spontaneous immune responses in patients with cancer and this feature makes them attractive targets for immunotherapy-based approaches. We analyzed mRNA expression of 37 testis-restricted CT genes in a discovery set of 18 meningiomas by reverse transcription PCR. The overall frequency of expression of CT genes ranged from 5.6% to 27.8%. The most frequently expressed was NY-ESO-1, in 5 patients (27.8%). We subsequently analyzed NY-ESO-1 protein expression in a larger set of meningiomas by immunohistochemistry and found expression in 108 of 110 cases. In some cases, NY-ESO-1 expression was diffused and homogenous, but in most instances it was heterogeneous. Importantly, NY-ESO-1 expression was positively correlated with higher grade and patients presenting with higher levels of NY-ESO-1 staining had significantly worse disease-free and overall survival. We have also shown that NY-ESO-1 expression may lead to humoral immune response in patients with meningioma. Considering the limited treatment options for patients with meningioma, the potential of NY-ESO-1-based immunotherapy should be explored.

    View details for DOI 10.1158/2326-6066.CIR-13-0029

    View details for Web of Science ID 000340030400005

    View details for PubMedID 24777967

  • 5-azacytidine reduces methylation, promotes differentiation and induces tumor regression in a patient-derived IDH1 mutant glioma xenograft ONCOTARGET Borodovsky, A., Salmasi, V., Turcan, S., Fabius, A. W., Baia, G. S., Eberhart, C. G., Weingart, J. D., Gallia, G. L., Baylin, S. B., Chan, T. A., Riggins, G. J. 2013; 4 (10): 1737-1747

    Abstract

    Somatic mutations in Isocitrate Dehydrogenase 1 (IDH1) are frequent in low grade and progressive gliomas and are characterized by the production of 2-hydroxyglutarate (2-HG) from ?-ketoglutarate by the mutant enzyme. 2-HG is an "oncometabolite" that competitively inhibits ?-KG dependent dioxygenases resulting in various widespread cellular changes including abnormal hypermethylation of genomic DNA and suppression of cellular differentiation. Despite the growing understanding of IDH mutant gliomas, the development of effective therapies has proved challenging in part due to the scarcity of endogenous mutant in vivo models. Here we report the generation of an endogenous IDH1 anaplastic astrocytoma model which rapidly grows in vivo, produces 2-HG and exhibits DNA hypermethylation. Using this model, we have demonstrated the preclinical efficacy and mechanism of action of the FDA approved demethylating drug 5-azacytidine in vivo. Long term administration of 5-azacytidine resulted in reduction of DNA methylation of promoter loci, induction of glial differentiation, reduction of cell proliferation and a significant reduction in tumor growth. Tumor regression was observed at 14 weeks and subsequently showed no signs of re-growth at 7 weeks despite discontinuation of therapy. These results have implications for clinical trials of demethylating agents for patients with IDH mutated gliomas.

    View details for Web of Science ID 000327401100021

    View details for PubMedID 24077805

  • Exomic Sequencing of Four Rare Central Nervous System Tumor Types ONCOTARGET Bettegowda, C., Agrawal, N., Jiao, Y., Wang, Y., Wood, L. D., Rodriguez, F. J., Hruban, R. H., Gallia, G. L., Binder, Z. A., Riggins, C. J., Salmasi, V., Riggins, G. J., Reitman, Z. J., Rasheed, A., Keir, S., Shinjo, S., Marie, S., McLendon, R., Jallo, G., Vogelstein, B., Bigner, D., Yan, H., Kinzler, K. W., Papadopoulos, N. 2013; 4 (4): 572-583

    Abstract

    A heterogeneous population of uncommon neoplasms of the central nervous system (CNS) cause significant morbidity and mortality. To explore their genetic origins, we sequenced the exomes of 12 pleomorphic xanthoastrocytomas (PXA), 17 non-brainstem pediatric glioblastomas (PGBM), 8 intracranial ependymomas (IEP) and 8 spinal cord ependymomas (SCEP). Analysis of the mutational spectra revealed that the predominant single base pair substitution was a C:G>T:A transition in each of the four tumor types. Our data confirm the critical roles of several known driver genes within CNS neoplasms, including TP53 and ATRX in PGBM, and NF2 in SCEPs. Additionally, we show that activating BRAF mutations play a central role in both low and high grade glial tumors. Furthermore, alterations in genes coding for members of the mammalian target of rapamycin (mTOR) pathway were observed in 33% of PXA. Our study supports the hypothesis that pathologically similar tumors arising in different age groups and from different compartments may represent distinct disease processes with varied genetic composition.

    View details for Web of Science ID 000318783800010

    View details for PubMedID 23592488

  • Expanded endonasal endoscopic approach for resection of a growth hormone-secreting pituitary macroadenoma coexistent with a cavernous carotid artery aneurysm JOURNAL OF CLINICAL NEUROSCIENCE Xia, X., Ramanathan, M., Orr, B. A., Salmasi, V., Salvatori, R., Reh, D. D., Gallia, G. L. 2012; 19 (10): 1437-1441

    Abstract

    The co-existence of pituitary adenomas (PA) and carotid artery aneurysms has been described and may be particularly frequent in acromegaly. The co-occurrence of an intracranial aneurysm in the setting of a PA presents significant risk to the patient, particularly when the aneurysm is within or near the operative field. We describe a 48-year-old, right-handed female patient with a large skull base lesion who had a left cavernous carotid artery aneurysm detected on her preoperative imaging studies. This patient was managed using a staged approach. She first underwent endovascular stent-assisted coiling of the aneurysm followed, six months later, by resection of the tumor via an expanded endonasal endoscopic approach. Histopathological analysis revealed a pituitary macroadenoma with neuronal metaplasia. Angiographic embolization followed by an expanded endonasal endoscopic approach is a safe and effective treatment for such lesions. Vascular imaging studies and a low index for suspicion are required for preoperative identification of such complex situations.

    View details for DOI 10.1016/j.jocn.2011.11.032

    View details for Web of Science ID 000309640500024

    View details for PubMedID 22836036

  • Chemotherapy within 30 days before surgery does not augment postoperative mortality and morbidity CANADIAN JOURNAL OF ANESTHESIA-JOURNAL CANADIEN D ANESTHESIE Turan, A., Shao, D., Salmasi, V., Honar, H., Atim, A., Dalton, J. E., Saager, L., Sessler, D. I. 2012; 59 (8): 758-765

    Abstract

    Preoperative chemotherapy is frequently given to shrink or decrease the chance of metastasis. However, chemotherapy has well-recognized side effects that may complicate the perioperative period. We therefore tested the hypotheses that chemotherapy within 30 days before cancer surgery is associated with an increased risk of mortality and with a composite of major morbidities within 30 postoperative days.We evaluated 971,455 patients from the American College of Surgeons National Surgical Quality Improvement Program database. Patients were defined as having chemotherapy when they were given any chemotherapy for malignancy within 30 days before surgery. We successfully matched 1,348 pairs of chemotherapy recipients and non-recipients.Twenty-one of the 1,348 (1.6%) non-chemotherapy patients died within 30 days after surgery compared with 30 of the 1,348 (2.2%) chemotherapy patients. The odds of mortality were not statistically different between groups based on our logistic regression model [odds ratio (OR) = 1.47; 95% confidence interval (CI) 0.82 to 2.64; P = 0.19]. The most common complication observed was wound infection in 13.1% of non-chemotherapy patients compared with 14.2% of the chemotherapy patients. There was similarly no difference between groups for the collapsed composite of major morbidities [OR = 1.17; 95% CI 0.97 to 1.42; P = 0.09].Preoperative use of neoadjuvant chemotherapy in cancer patients undergoing resection surgeries was not associated with a higher rate of early postoperative complications or mortality.

    View details for DOI 10.1007/s12630-012-9735-3

    View details for Web of Science ID 000306543700005

    View details for PubMedID 22638675

  • Establishment and characterization of a primary human chordoma xenograft model Laboratory investigation JOURNAL OF NEUROSURGERY Siu, I., Salmasi, V., Orr, B. A., Zhao, Q., Binder, Z. A., Tran, C., Ishii, M., Riggins, G. J., Hann, C. L., Gallia, G. L. 2012; 116 (4): 801-809

    Abstract

    Chordomas are rare tumors arising from remnants of the notochord. Because of the challenges in achieving a complete resection, the radioresistant nature of these tumors, and the lack of effective chemotherapeutics, the median survival for patients with chordomas is approximately 6 years. Reproducible preclinical model systems that closely mimic the original patient's tumor are essential for the development and evaluation of effective therapeutics. Currently, there are only a few established chordoma cell lines and no primary xenograft model. In this study, the authors aimed to develop a primary chordoma xenograft model.The authors implanted independent tumor samples from 2 patients into athymic nude mice. The resulting xenograft line was characterized by histopathological analysis and immunohistochemical staining. The patient's tumor and serial passages of the xenograft were genomically analyzed using a 660,000 single-nucleotide polymorphism array.A serially transplantable xenograft was established from one of the 2 patient samples. Histopathological analysis and immunohistochemical staining for S100 protein, epithelial membrane antigen, and cytokeratin AE1/AE3 of the primary patient sample and the xenografts confirmed that the xenografts were identical to the original chordoma obtained from the patient. Immunohistochemical staining and western blot analysis confirmed the presence of brachyury, a recently described marker of chordomas, in the tumor from the patient and each of the xenografts. Genome-wide variation was assessed between the patient's tumor and the xenografts and was found to be more than 99.9% concordant.To the best of their knowledge, the authors have established the first primary chordoma xenograft that will provide a useful preclinical model for this disease and a platform for therapeutic development.

    View details for DOI 10.3171/2011.12.JNS111123

    View details for Web of Science ID 000301805500019

    View details for PubMedID 22283186

  • Expanded endonasal endoscopic approach for resection of a skull base low-grade smooth muscle neoplasm CHILDS NERVOUS SYSTEM Salmasi, V., Reh, D. D., Blitz, A. M., Argani, P., Ishii, M., Gallia, G. L. 2012; 28 (1): 151-158

    Abstract

    Benign smooth muscle tumors rarely occur in the head and neck and, to the best of our knowledge, have not been reported in the pterygopalatine fossa. In this report, we describe a 15-year-old adolescent who presented with facial pain and was found to have a large skull base tumor centered in the pterygopalatine fossa. The patient underwent an expanded endonasal endoscopic approach for complete resection of this lesion with resolution of his symptoms. Pathology revealed a well-differentiated smooth muscle neoplasm consistent with a leiomyoma. This case adds to the growing body of literature supporting a role for endoscopic procedures in the treatment of skull base pathologies in pediatric patients.

    View details for DOI 10.1007/s00381-011-1589-4

    View details for Web of Science ID 000298995300026

    View details for PubMedID 22041975

  • Endonasal endoscopic resection of esthesioneuroblastoma: the Johns Hopkins Hospital experience and review of the literature NEUROSURGICAL REVIEW Gallia, G. L., Reh, D. D., Salmasi, V., Blitz, A. M., Koch, W., Ishii, M. 2011; 34 (4): 465-474

    Abstract

    Esthesioneuroblastoma is an uncommon malignant tumor originating in the upper nasal cavity. The surgical treatment for this tumor has traditionally been via an open craniofacial resection. Over the past decade, there has been tremendous development in endoscopic techniques. In this report, we performed a retrospective analysis of patients with esthesioneuroblastomas treated with a purely endonasal endoscopic approach and resection at the Johns Hopkins Hospital between January 2005 and April 2010. A total of eight patients with esthesioneuroblastoma, five men and three women, were identified. Six patients were treated for primary disease, and two were treated for tumor recurrence. The modified Kadish staging was A in one patient (12.5%), B in two patients (25%), C in four patients (50%), and D in one patient (12.5%). All patients had a complete resection with negative intraoperative margins. One patient had intraoperative hypertension; there were no perioperative complications. With a mean follow-up of over 27 months, all patients are without evidence of disease. In addition, we reviewed the literature and identified several overlapping case series of patients with esthesioneuroblastoma treated via a purely endoscopic technique. Our series adds to the growing experience of expanded endonasal endoscopic surgery in the treatment of skull base tumors including esthesioneuroblastoma. Longer follow-up on a larger number of patients is required to further demonstrate the utility of endoscopic approaches in the management of this malignancy.

    View details for DOI 10.1007/s10143-011-0329-2

    View details for Web of Science ID 000294838800012

    View details for PubMedID 21655908

  • Expanded endonasal endoscopic approach for resection of a large skull base aneurysmal bone cyst in a pediatric patient with extensive cranial fibrous dysplasia CHILDS NERVOUS SYSTEM Salmasi, V., Blitz, A. M., Ishii, M., Gallia, G. L. 2011; 27 (4): 649-656

    Abstract

    Aneurysmal bone cysts (ABCs) are uncommon non-neoplastic, hemorrhagic, and expansile osseous lesions. These lesions most commonly occur in the first two decades of life and affect the long bones and spinal column. Skull base involvement is rare. The authors report the case of a 16-year-old boy who presented with acute visual decline and was found to have a large skull base ABC centered in the sphenoid sinus. In addition, the patient had extensive cranial fibrous dysplasia. The patient underwent a staged expanded endonasal endoscopic approach for complete resection of this lesion with excellent return of his vision. This case adds to the growing body of evidence supporting a role for expanded endonasal endoscopic procedures in pediatric patients with skull base pathologies.

    View details for DOI 10.1007/s00381-010-1341-5

    View details for Web of Science ID 000288256000017

    View details for PubMedID 21132434

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