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.
- Pain Management
- Spinal Cord Stimulation
- Dorsal Root Ganglion Stimulation
- Peripheral Nerve Stimulation
- Minimally Invasive Spine Interventions
- Back Pain
- Post-Laminectomy Syndrome
- Neuropathic Pain
- Postherpetic Neuralgia
- Spinal Stenosis
- Perioperative Pain Management
Assistant Professor - University Medical Line, 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)
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
Comparing Effectiveness of Duloxetine and Desipramine in Patients With Chronic Pain: A Pragmatic Trial Using Point of Care Randomization
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.
Comparing Long-term Effectiveness of High Frequency and Burst Spinal Cord Stimulation
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 Pragmatic Effectiveness Comparison
Chronic pain is a major healthcare problem with an annual cost of above $600 billion. The quality of data available for treatments of chronic pain is not optimal. Generalizability of explanatory randomized controlled trial data is problematic as these trials exclude up to 90% of patients: leaving out real-world patients with serious medical and psychological comorbidities. Pragmatic trials embedded in patient care compare effectiveness of currently used treatments in real-world application leading to findings that generalize to broader range of patients. The changes in clinical practice and workflow necessary to integrate this type of research within patient care present pragmatic challenges. In this research, the overall objective is to overcome these challenges using an open-source learning health care system - CHOIR. CHOIR is currently used to track patients' clinical trajectory and treatment response across multiple academic sites resulting in over 25 publications characterizing chronic pain. Through the pilot studies, the investigators have already developed a point-of-care randomization for CHOIR that facilitates integration of research and patient care by allowing the physicians to randomize patients during clinic visits. The investigators have already demonstrated feasibility of the randomization and data collection platform in two ongoing pilot pragmatic clinical trials. The investigators are proposing to better integrate pragmatic research within clinical practice through conducting a randomized comparative effectiveness trial in 450 patients with chronic pain comparing effectiveness of anti-convulsants and anti-depressants (two most commonly used classes of medications for treatment of chronic pain). The investigators will also perform a qualitative interview with all physicians in our clinic to study the impact of integrating pragmatic research into clinical care. The investigators will use the data available in CHOIR as well as the real-world data generated from this clinical trial to build, validate and test a model to predict what clinical characteristics can predict response to either of these classes of medications. The proposed study is the first step to use flexible point-of-care randomization to compare effectiveness of different treatments in different subgroups of patients whenever equipoise exists. The prediction model will guide decision making process of clinicians choosing between these medications based on clinical characteristics of individual patients.
Graduate and Fellowship Programs
Pain Management (Fellowship Program)
Pragmatic Comparative Effectiveness Trials and Learning Health Systems in Pain Medicine: Opportunities and Challenges.
2023; 41 (2): 503-517
Large randomized clinical trials or aggregates of clinical trials represent the highest levels of clinical evidence because they minimize different sources of confounding and bias. The current review provides an in-depth discussion of the challenges faced and methods we can use to overcome these obstacles to tailor novel designs of pragmatic effectiveness trials to pain medicine. The authors describe their experiences with an open-source learning health system to collect high-quality evidence and conduct pragmatic clinical trials within a busy academic pain center.
View details for DOI 10.1016/j.anclin.2023.03.010
View details for PubMedID 37245953
Transitional Pain Medicine; New Era, New Opportunities, and New Journey.
2023; 41 (2): 383-394
Chronic postsurgical pain (CPSP), also known as persistent postsurgical pain (PPSP), is pain that develops or increases in intensity after a surgical procedure and lasts more than 3 months. Transitional pain medicine is the medical field that focuses on understanding the mechanisms of CPSP and defining risk factors and developing preventive treatments. Unfortunately, one significant challenge is the risk of developing opioid use dependence. Multiple risk factors have been discovered, with the most common, and modifiable, being uncontrolled acute postoperative pain; preoperative anxiety and depression; and preoperative site pain, chronic pain, and opioid use.
View details for DOI 10.1016/j.anclin.2023.03.007
View details for PubMedID 37245949
Clinical Approach to Chronic Pain due to Perioperative Nerve Injury.
2023; 41 (2): 489-502
Perioperative nerve injuries are common and may be prevented. The estimated incidence of perioperative nerve injury is 10% to 50%. However, most of these injuries are minor and self-recovering. Severe injuries account for up to 10%. Potential mechanisms of injury are nerve stretch, compression, hypoperfusion, direct nerve trauma, or injury during vessel cannulation. Nerve injury pain usually presents as neuropathic pain ranging from mild to severe mononeuropathy and extends to the disabling complex regional pain syndrome. This review provides a clinical approach to subacute and chronic pain secondary to perioperative nerve injury, presentation, and management.
View details for DOI 10.1016/j.anclin.2023.03.009
View details for PubMedID 37245952
- Durable Chronic Low Back Pain Reductions to 24-Months Post-Treatment for An Accessible, 8-Week, In-Home Behavioral Skills-Based Virtual Reality Program: A Randomized Controlled Trial. Pain medicine (Malden, Mass.) 2023
- In-home virtual reality program for chronic low back pain: durability of a randomized, placebo-controlled clinical trial to 18 months post-treatment. Regional anesthesia and pain medicine 2022
Association of cannabis and/or opioid with quality of life and healthcare utilization in patients with chronic pain.
Frontiers in pain research (Lausanne, Switzerland)
2022; 3: 1015605
Opioids have been commonly used to treat chronic pain, but they are associated with significant morbidity and mortality. Cannabis has been advocated as an alternative; however, a growing number of patients are now using a combination of opioid and cannabis and the impact of this combination is not well-studied.We characterized use of opioid and/or cannabis in patients with chronic pain; and compared utilization of healthcare resources.We conducted a cross-sectional study to determine if measures of physical, psychological and social functioning differed among patients according to whether they used opioids and/or cannabis. We used our learning healthcare system - CHOIR - to capture NIH Patient Reported Outcomes Measure Information System surveys, and legacy pain and treatment specific questions.Patients who report use of opioid and/or cannabis experience higher levels of physical, psychological and social distress. After adjusting for inversed weight of propensity scores, they have higher odds of visiting an emergency room, staying overnight at the hospital, and visiting a physician.Our results show that use of opioid and/or cannabis is associated with worse baseline characteristics and outcomes. Our study however cannot determine if worse outcomes are due to the opioids and/or cannabis or simply that these patients are worse off before using opioids and/or cannabis. Thus, it is important to characterize the trajectory of these patients in a prospective longitudinal study.
View details for DOI 10.3389/fpain.2022.1015605
View details for PubMedID 36506271
View details for PubMedCentralID PMC9729730
A literature review of the impact of exclusion criteria on generalizability of clinical trial findings to patients with chronic pain
2022; 7 (6): e1050
The ability of clinical trials to inform the care of chronic pain may be limited if only an unrepresentative subset of patients are allowed to enroll. We summarize and report new insights on published studies that report on how trial exclusions affect the generalizability of their results. We conducted a PubMed search on the following terms: (("eligibility criteria" AND generalizability) OR ("exclusion criteria" AND generalizability) OR "exclusion criteria"[ti] OR "eligibility criteria"[ti]) AND pain. We only considered studies relevant if they analyzed data on (1) the prevalence and nature of exclusion criteria or (2) the impact of exclusion criteria on sample representativeness or study results. The 4 articles that were identified reported differences in patients who were included and excluded in different clinical trials: excluded patients were older, less likely to have a paid job, had more functional limitations at baseline, and used strong opioids more often. The clinical significance of these differences remains unclear. The pain medicine literature has very few published studies on the prevalence and impact of exclusion criteria, and the outcomes of excluded patients are rarely tracked. The frequent use of psychosocial exclusions is especially compromising to generalizability because chronic pain commonly co-occurs with psychiatric comorbidities. Inclusion of more representative patients in research samples can reduce recruitment barriers and broaden the generalizability of findings in patients with chronic pain. We also call for more studies that examine the use of exclusion criteria in chronic pain trials to better understand their implications.
View details for DOI 10.1097/PR9.0000000000001050
View details for Web of Science ID 000884105700002
View details for PubMedID 36398200
View details for PubMedCentralID PMC9663135
"My Surgical Success": Feasibility and Impact of a Single-Session Digital Behavioral Pain Medicine Intervention on Pain Intensity, Pain Catastrophizing, and Time to Opioid Cessation After Orthopedic Trauma Surgery-A Randomized Trial.
Anesthesia and analgesia
Behavioral pain treatments may improve postsurgical analgesia and recovery; however, effective and scalable options are not widely available. This study tested a digital perioperative behavioral medicine intervention in orthopedic trauma surgery patients for feasibility and efficacy for reducing pain intensity, pain catastrophizing, and opioid cessation up to 3 months after surgery.A randomized controlled clinical trial was conducted at an orthopedic trauma surgery unit at a major academic hospital to compare a digital behavioral pain management intervention ("My Surgical Success" [MSS]) to a digital general health education (HE) intervention (HE; no pain management skills). The enrolled sample included 133 patients; 84 patients were randomized (MSS, N = 37; HE, N = 47) and completed study procedures. Most patients received their assigned intervention within 3 days of surgery (85%). The sample was predominantly male (61.5%), White (61.9%), and partnered (65.5%), with at least a bachelor's degree (69.0%). Outcomes were collected at 1-3 months after intervention through self-report e-surveys and electronic medical record review; an intention-to-treat analytic framework was applied. Feasibility was dually determined by the proportion of patients engaging in their assigned treatment and an application of an 80% threshold for patient-reported acceptability. We hypothesized that MSS would result in greater reductions in pain intensity and pain catastrophizing after surgery and earlier opioid cessation compared to the digital HE control group.The engagement rate with assigned interventions was 63% and exceeded commonly reported rates for fully automated Internet-based e-health interventions. Feasibility was demonstrated for the MSS engagers, with >80% reporting treatment acceptability. Overall, both groups improved in the postsurgical months across all study variables. A significant interaction effect was found for treatment group over time on pain intensity, such that the MSS group evidenced greater absolute reductions in pain intensity after surgery and up to 3 months later (treatment × time fixed effects; F = 5.23; P = .024). No statistically significant between-group differences were observed for time to opioid cessation or for reductions in pain catastrophizing (F = 0.20; P = .653), although the study sample notably had subclinical baseline pain catastrophizing scores (M = 14.10; 95% confidence interval, 11.70-16.49).Study findings revealed that a fully automated behavioral pain management skills intervention (MSS) may be useful for motivated orthopedic trauma surgery patients and reduce postsurgical pain up to 3 months. MSS was not associated with reduced time to opioid cessation compared to the HE control intervention.
View details for DOI 10.1213/ANE.0000000000006088
View details for PubMedID 35696706
- Correction: Durability of the Treatment Effects of an 8-Week Self-administered Home-Based Virtual Reality Program for Chronic Low Back Pain: 6-Month Follow-up Study of a Randomized Clinical Trial. Journal of medical Internet research 2022; 24 (6): e40038
Durability of the Treatment Effects of an 8-Week Self-administered Home-Based Virtual Reality Program for Chronic Low Back Pain: 6-Month Follow-up Study of a Randomized Clinical Trial (vol 24, e37480, 2022)
JOURNAL OF MEDICAL INTERNET RESEARCH
2022; 24 (6)
View details for Web of Science ID 000966321600004
Durability of the Treatment Effects of an 8-Week Self-administered Home-Based Virtual Reality Program for Chronic Low Back Pain: Follow-up Study of a Randomized Clinical Trial.
Journal of medical Internet research
2022; 24 (5): e37480
BACKGROUND: We previously reported the efficacy of an 8-week home-based therapeutic immersive virtual reality (VR) program in a double-blind randomized placebo-controlled study. Community-based adults with self-reported chronic low back pain were randomized 1:1 to receive either (1) a 56-day immersive therapeutic pain relief skills VR program (EaseVRx) or (2) a 56-day sham VR program. Immediate posttreatment results revealed the superiority of therapeutic VR over sham VR for reducing pain intensity; pain-related interference with activity, mood, and stress (but not sleep); physical function; and sleep disturbance. At 3 months posttreatment, therapeutic VR maintained superiority for reducing pain intensity and pain-related interference with activity, stress, and sleep (new finding).OBJECTIVE: This study assessed between-group and within-group treatment effects 6 months posttreatment to determine the extended efficacy, magnitude of efficacy, and clinical importance of home-based therapeutic VR.METHODS: E-surveys were deployed at pretreatment, end-of-treatment, and posttreatment months 1, 2, 3, and 6. Self-reported data for 188 participants were analyzed in a mixed-model framework using a marginal model to allow for correlated responses across the repeated measures. Primary outcomes were pain intensity and pain-related interference with activity, mood, stress, and sleep at 6 months posttreatment. Secondary outcomes were Patient-Reported Outcome Measurement Information System (PROMIS) sleep disturbance and physical function.RESULTS: Therapeutic VR maintained significant and clinically meaningful effects 6 months posttreatment and remained superior to sham VR for reducing pain intensity and pain-related interference with activity, stress, and sleep (ds=0.44-0.54; P<.003). Between-group comparisons for physical function and sleep disturbance showed superiority of EaseVRx over sham VR (ds=0.34; P=.02 and ds=0.46; P<.001, respectively). Participants were encouraged to contact study staff with any problems experienced during treatment; however, no participants contacted study staff to report adverse events of any type, including nausea and motion sickness.CONCLUSIONS: Our 8-week home-based VR pain management program caused important reductions in pain intensity and interference up to 6 months after treatment. Additional studies are needed in diverse samples.TRIAL REGISTRATION: ClinicalTrials.gov NCT04415177; https://clinicaltrials.gov/ct2/show/NCT04415177.INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/25291.
View details for DOI 10.2196/37480
View details for PubMedID 35612905
Considerations in Permanent Implantation of Peripheral Nerve Stimulation (PNS) for Chronic Neuropathic Pain: An International Cross Sectional Survey of Implanters.
Pain practice : the official journal of World Institute of Pain
INTRODUCTION: Novel minimally invasive short-term and long-term peripheral nerve stimulation (PNS) systems have revolutionized targeted treatment of chronic neuropathic pain. We present an international survey of PNS-implanting pain physicians to assess what factors they consider when offering permanent PNS.METHODS: This cross-sectional study consisted of a survey (Qualtrics) that was distributed to PNS-implanting physicians in a device supplier's entire email database on November 13, 2020, with 3 weeks of response time. Physicians' contact information in the form of their email addresses had been previously collected by the supplier upon device distribution with permission to use survey responses for research.RESULTS: Of 2,032 database physicians, 40 physicians representing 37 institutions responded to the survey. The most common application of PNS was mononeuropathic pain (57%). The most frequently targeted nerve was the suprascapular nerve (29%). 14% of physicians reported 81-100% of their implants were dual-lead. The representative physicians ranged broadly in their most frequently-targeted nerves. Although mononeuropathic pain was the most common indication for PNS, there was still varied response regarding other indications such as CRPS and post-surgical chronic pain.CONCLUSION: In context of a low response rate, identifying such factors can help update the prevailing treatment algorithm for interventional therapies, assist pain physicians in better identifying which patients are the best candidates for PNS, and inform future clinical trial design on PNS efficacy.
View details for DOI 10.1111/papr.13105
View details for PubMedID 35178863
Management of Postoperative Pain in Patients Following Spine Surgery: A Narrative Review.
International journal of general medicine
2022; 15: 4535-4549
Perioperative pain management is a unique challenge in patients undergoing spine surgery due to the increased incidence of both pre-existing chronic pain conditions and chronic postsurgical pain. Peri-operative planning and counseling in spine surgery should involve an interdisciplinary approach that includes consideration of patient-level risk factors, as well as pharmacologic and non-pharmacologic pain management techniques. Consideration of psychological factors and patient focused education as an adjunct to these measures is paramount in developing a personalized perioperative pain management plan. Understanding the currently available body of knowledge surrounding perioperative opioid management, management of opioid use disorder, regional/neuraxial anesthetic techniques, ketamine/lidocaine infusions, non-opioid oral analgesics, and behavioral interventions can be useful in developing a comprehensive, multi-modal treatment plan among patients undergoing spine surgery. Although many of these techniques have proved efficacious in the immediate postoperative period, long-term follow-up is needed to define the impact of such approaches on persistent pain and opioid use. Future techniques involving the use of precision medicine may help identify phenotypic and physiologic characteristics that can identify patients that are most at risk of developing persistent postoperative pain after spine surgery.
View details for DOI 10.2147/IJGM.S292698
View details for PubMedID 35528286
Stanford pragmatic effectiveness comparison (SPEC) protocol: Comparing long-term effectiveness of high-frequency and burst spinal cord stimulation in real-world application.
Contemporary clinical trials
OBJECTIVES: High-frequency and burst stimulation are newer waveforms that have demonstrated promise compared to traditional tonic spinal cord stimulation (SCS), but more studies are needed to compare their effectiveness. We report the study methods for an ongoing, single center, pragmatic randomized clinical trial to compare the effectiveness of high-frequency and burst SCS in patients with chronic back and/or leg pain.MATERIALS AND METHODS: Participants who are candidates for spinal cord stimulation are enrolled and screened. Participants will be randomly assigned using point-of-care randomization to receive either high-frequency or burst SCS. Data collection will be through Stanford Pain Management Center's learning healthcare system: CHOIR. CHOIR surveys include National Institutes of Health Patient Reported Outcomes Measurement Information System item banks, a body map, questions about pain intensity, pain catastrophizing scale, and questions about patients' pain experience and healthcare utilization. Participants will complete online surveys at baseline and then 1, 3, 6, 12, 18, 24 and 36 months after their device implant. All participants will use our routine process of trial and implant. Reported adverse events are monitored throughout the study. Our primary outcome is change from baseline in pain intensity at 12 months.RESULTS: We hypothesize that high-frequency SCS is more effective than burst SCS in improving pain, physical function and pain interference in participants with chronic low back and/or leg pain.CONCLUSIONS: The pragmatic nature of our proposed trial enables us to recruit a larger participant cohort faster and to follow up these participants longer than currently published clinical trials.
View details for DOI 10.1016/j.cct.2021.106324
View details for PubMedID 33621631
Double-blind, randomized placebo-controlled trial of 8-week self-administered at-home behavioral skills-based virtual reality (VR) for chronic low back pain (during COVID-19).
Journal of medical Internet research
Background: Chronic low back pain is the most prevalent chronic pain condition worldwide and access to behavioral pain treatment is limited. Virtual reality (VR) is an immersive technology that may provide effective behavioral therapeutics for chronic pain.Objective: To conduct a double-blind, parallel arm, single cohort, remote, randomized placebo-controlled trial for a self-administered behavioral skills-based VR program in community-based individuals with self-reported chronic low back pain during the COVID-19 pandemic.Methods: A national online convenience sample of individuals with self-reported non-malignant low back pain > 6 months duration and with average pain intensity > 4/10 was enrolled and randomized 1:1 to one of two daily (56-day) VR programs: (1) EaseVRx (immersive pain relief skills VR program); or (2) Sham VR (2D nature content delivered in a VR headset). Objective device use data and self-reported data were collected. The primary outcomes were the between-group effect of EaseVRx versus Sham VR across time points, and the between-within interaction effect representing the change in average pain intensity and pain-related interference with activity, stress, mood, and sleep over time (baseline to end-of-treatment at day 56). Secondary outcomes were global impression of change and change in physical function, sleep disturbance, pain self-efficacy, pain catastrophizing, pain acceptance, pain medication use, and user satisfaction. Analytic methods included intention-to-treat and a mixed-model framework.The study sample was 179 adults (female: 77%; Caucasian: 91%; at least some college education: 92%; mean age: 51.5 years, SD=13.1; average pain intensity: 5/10, SD=1.2; back pain duration >5 years: 67%). No group differences were found for any baseline variable or treatment engagement. User satisfaction ratings were higher for EaseVRx vs. Sham VR (p<0.0001). For the between-groups factor, EaseVRx was superior to Sham VR for all primary outcomes (highest p-value = .0090), and between-groups Cohen's d effect sizes ranged from 0.40 to 0.49 indicating superiority was moderately clinically meaningful. For EaseVRx, large pre-post effect sizes ranged from 1.17-1.3 and met moderate to substantial clinical importance for reduced pain intensity and pain-related interference with activity, mood, and stress. Between group comparisons for physical function and sleep disturbance showed superiority for the EaseVRx group vs. the Sham VR group (p=0.0224 and p=.0132, respectively). Pain catastrophizing, pain self-efficacy, pain acceptance, prescription opioid use (morphine milligram equivalent; MME) did not reach statistical significance for either group. Use of over-the-counter analgesic use was reduced for EaseVRx (p<0.01) but not for ShamVR.EaseVRx had high user satisfaction and superior and clinically meaningful symptom reduction for average pain intensity and pain-related interference with activity, mood, and stress compared to sham VR. Additional research is needed to determine durability of treatment effects and to characterize mechanisms of treatment effects. Home-based VR may expand access to effective and on-demand non-pharmacologic treatment for chronic low back pain.ClinicalTrials.gov, NCT04415177.RR2-25291.
View details for DOI 10.2196/26292
View details for PubMedID 33484240
Three-month follow-up results of a double-blind, randomized placebo-controlled trial of 8-week self-administered at-home behavioral skills-based virtual reality (VR) for chronic low back pain.
The journal of pain
Prior work established post-treatment efficacy for an 8-week home-based therapeutic virtual reality (VR) program in a double-blind, parallel arm, randomized placebo-controlled study. Participants were randomized 1:1 to one of two 56-day VR programs: (1) a therapeutic immersive pain relief skills VR program; or (2) a Sham VR program within an identical commercial VR headset. Immediate post-treatment results demonstrated clinically meaningful and superior reduction for therapeutic VR compared to Sham VR for average pain intensity, indices of pain-related interference (activity, mood, stress but not sleep), physical function and sleep disturbance. The objective of the current report was to quantify treatment effects to post-treatment month 3 and describe durability of effects. Intention-to-treat analyses revealed sustained benefits for both groups and superiority for therapeutic VR for pain intensity and multiple indices of pain-related interference (activity, stress, and newly for sleep; effect sizes ranged from drm = 0.56 to 0.88) and physical function from pre-treatment to post-treatment month 3. The between-group difference for sleep disturbance was non-significant and pain-interference with mood did not survive multiplicity correction at 3 months. For most primary and secondary outcomes, treatment effects for therapeutic VR showed durability and maintained superiority to Sham VR in the 3-month post-treatment period.
View details for DOI 10.1016/j.jpain.2021.12.002
View details for PubMedID 34902548
Development and validation of the Collaborative Health Outcomes Information Registry body map.
2021; 6 (1): e880
Introduction: Critical for the diagnosis and treatment of chronic pain is the anatomical distribution of pain. Several body maps allow patients to indicate pain areas on paper; however, each has its limitations.Objectives: To provide a comprehensive body map that can be universally applied across pain conditions, we developed the electronic Collaborative Health Outcomes Information Registry (CHOIR) self-report body map by performing an environmental scan and assessing existing body maps.Methods: After initial validation using a Delphi technique, we compared (1) pain location questionnaire responses of 530 participants with chronic pain with (2) their pain endorsements on the CHOIR body map (CBM) graphic. A subset of participants (n = 278) repeated the survey 1 week later to assess test-retest reliability. Finally, we interviewed a patient cohort from a tertiary pain management clinic (n = 28) to identify reasons for endorsement discordances.Results: The intraclass correlation coefficient between the total number of body areas endorsed on the survey and those from the body map was 0.86 and improved to 0.93 at follow-up. The intraclass correlation coefficient of the 2 body map graphics separated by 1 week was 0.93. Further examination demonstrated high consistency between the questionnaire and CBM graphic (<10% discordance) in most body areas except for the back and shoulders (15-19% discordance). Participants attributed inconsistencies to misinterpretation of body regions and laterality, the latter of which was addressed by modifying the instructions.Conclusions: Our data suggest that the CBM is a valid and reliable instrument for assessing the distribution of pain.
View details for DOI 10.1097/PR9.0000000000000880
View details for PubMedID 33490848
Peripheral Nerve Stimulation for Occipital Neuralgia.
Pain medicine (Malden, Mass.)
2020; 21 (Supplement_1): S13–S17
BACKGROUND: Chronic headaches are the second most prevalent disease and second most common cause for years lived with disability worldwide. Occipital neuralgia can cause headaches or be present in addition to other more prevalent causes of headache. If these headaches fail to respond to conservative and pharmacological therapy, physicians proceed to more invasive treatments, starting with infiltration of the greater occipital nerve with local anesthetic with or without corticosteroids, followed by nerve ablation or stimulation. Occipital nerve stimulation gained more popularity as the technology improved and more pain physicians received training on interventional procedures.METHODS: In this manuscript, we are presenting our experience with ultrasound-guided implant of occipital nerve stimulators using peripheral nerve stimulator systems. After confirming appropriateness of treatment by a successful occipital nerve block (i.e., resulting in >50% relief in patients' pain intensity), we implanted five stimulator systems in three patients (two bilateral).RESULTS: We followed these patients for an average of eight months, and the average pain reduction was 50%. We did not observe any adverse events during or immediately after surgery. One patient developed an adverse reaction to the adhesive of the battery transmitter, but it was not severe enough to stop her from using the stimulator.CONCLUSIONS: Considering the ease of implant and minimal side effects, implant of peripheral nerve stimulators to stimulate the occipital nerve is a promising treatment modality for patients with chronic headache who present with features of occipital neuralgia. However, wider use of this treatment modality is subject to further studies.
View details for DOI 10.1093/pm/pnaa083
View details for PubMedID 32804226
Peripheral Nerve Stimulation for Pudendal Neuralgia: A Technical Note.
Pain medicine (Malden, Mass.)
2020; 21 (Supplement_1): S51–S55
BACKGROUND: Pudendal neuropathy is a chronic, disabling form of perineal pain that involves the pudendal nerve, a mixed somatic and autonomic nerve that originates from sacral nerve roots. Peripheral nerve stimulation of the pudendal nerve can be useful to decrease symptom burden in patients who have failed initial conservative treatment modalities.METHODS: In this manuscript, we describe an approach to the placement of a peripheral nerve stimulator for the treatment of pudendal neuralgia. We present a case of complex pelvic neuropathy and review the factors that lead to successful placement. Technical aspects of stimulator placement and ultrasound landmarks are reviewed.RESULTS: A lateral to medial approach with ultrasound guidance at the level of the ischial spine is likely to facilitate proper lead placement along the course of the pudendal nerve. Aftercare and adherence to postimplant activity restrictions-particularly avoiding use of the extremes of hip flexion and extension for four weeks-lead to the absence of lead migration.CONCLUSIONS: Pudendal nerve stimulation is an emerging technique for neuromodulation of refractory pudendal neuralgia. Ultrasound-guided pudendal nerve stimulation is a viable technique for neuromodulation of pudendal neuralgia. Optimization of patient selection, ultrasound guidance, and proper adherence to postimplant activity restrictions may be helpful for long-term therapeutic success.
View details for DOI 10.1093/pm/pnaa171
View details for PubMedID 32804222
Outcomes of Sympathetic Blocks in the Management of Complex Regional Pain Syndrome: A Retrospective Cohort Study.
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.
2018; 9 (1): 5410
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
- Genomic analysis identifies frequent deletions of Dystrophin in olfactory neuroblastoma NATURE COMMUNICATIONS 2018; 9
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.
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
2016; 123 (3): 749-757
Clonidine is an α2-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
2016; 11 (3)
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
View details for PubMedCentralID PMC4814135
Identification of location of nerve catheters using pumping maneuver and M-Mode-a novel technique
JOURNAL OF CLINICAL ANESTHESIA
2015; 27 (4): 325-330
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
2015; 37 (6): E74-E80
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
2015; 122 (2): 276-285
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 ± 0.6°C. Sixty-four percent of the patients reached a core temperature threshold of <36°C 45 min after induction; 29% reached a core temperature threshold of <35.5°C. Nearly half the patients had continuous core temperatures <36°C for more than an hour, and 20% of the patients were <35.5°C for more than an hour. Twenty percent of patients had continuous core temperatures <36°C for more than 2 h, and 8% of the patients were below 35.5°C 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.
2014; 312 (21): 2254-2264
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 μmol/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
2014; 370 (16): 1504-1513
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
2014; 370 (16): 1494-1503
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
2013; 1 (5): 296-302
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
2013; 4 (10): 1737-1747
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 α-ketoglutarate by the mutant enzyme. 2-HG is an "oncometabolite" that competitively inhibits α-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
2013; 4 (4): 572-583
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
2012; 19 (10): 1437-1441
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
2012; 59 (8): 758-765
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
2012; 116 (4): 801-809
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
2012; 28 (1): 151-158
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
2011; 34 (4): 465-474
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
2011; 27 (4): 649-656
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