Gary Brenner | Massachusetts General Hospital (original) (raw)

Papers by Gary Brenner

Journal of Clinical Medicine, Apr 1, 2023

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Pain Physician, Jan 15, 2018

Background: We hypothesized that there is a gap between expectations and actual training in pract... more Background: We hypothesized that there is a gap between expectations and actual training in practice management for pain medicine fellows. Our impression is that many fellowships rely on residency training to provide exposure to business education. Unfortunately, pain management and anesthesiology business education are very different, as the practice settings are largely officeversus hospital-based, respectively. Objective: Because it is unclear whether pain management fellowships are providing practice management education and, if they do, whether the topics covered match the expectations of their fellows, we surveyed pain medicine program directors and fellows regarding their expectations and training in business management. Study Design: A survey. Setting: Academic pain medicine fellowship programs. Methods: After an exemption was obtained from the University of Texas Medical Branch Institutional Review Board (#13-030), an email survey was sent to members of the Association of Pain Program Directors to be forwarded to their fellows. Directors were contacted 3 times to maximize the response rate. The anonymous survey for fellows contained 21 questions (questions are shown in the results). Results: Fifty-nine of 84 program directors responded and forwarded the survey to their fellows. Sixty fellows responded, with 56 answering the survey questions. Limitations: The responder rate is a limitation, although similar rates have been reported in similar studies. Conclusions: The majority of pain medicine fellows receive some practice management training, mainly on billing documentation and preauthorization processes, while most do not receive business education (e.g., human resources, contracts, accounting/financial reports). More than 70% of fellows reported that they receive more business education from industry than from their fellowships, a result that may raise concerns about the independence of our future physicians from the industry. Our findings support the need for enhanced and structured business education during pain fellowship.

Journal of Neuroimmunology, Apr 1, 1992

The objective of this chapter is to cover the anatomy and signaling pathways that contribute to o... more The objective of this chapter is to cover the anatomy and signaling pathways that contribute to our understanding of signal transduction from the peripheral to the central nervous system. This chapter provides the basis for understanding pain pharmacology and various interventions undertaken by pain practitioners.

Springer eBooks, Sep 22, 2012

Painful disorders of the spine are among our most common medical complaints. Over a lifetime, 60–... more Painful disorders of the spine are among our most common medical complaints. Over a lifetime, 60–80 % of adults experience at least one significant episode of back pain. In a single year, 15–20 % will have back pain, and 2–5 % of the entire population will seek medical attention for back pain. Low back pain has been estimated as the fifth leading cause of all medical visits and the second leading cause of symptom-related medical visits. In the United States, the estimated annual cost of back pain is 20billionto20 billion to 20billionto50 billion. In particular, low back pain is one of the most important factors in medical costs and disability.

Antioxidants, Oct 27, 2022

Anesthesiology, May 1, 2015

D URING the past decade, there has been a rapid increase in the use of epidural steroid injection... more D URING the past decade, there has been a rapid increase in the use of epidural steroid injections (ESIs) for the treatment of spinal pain. The annual number of epidural injections performed on Medicare beneficiaries has approximately doubled since 2000; in 2012 alone, there were more than 2 million claims submitted to Medicare for ESIs. 1 Because many of the conditions treated by ESI are common in the elderly, the number of injections is likely to increase as the U.S. population ages; however, this is unquestionably also dependent on whether Medicare and other payers continue to reimburse for the procedure. Although rare, ESI can be associated with catastrophic, even fatal, neurological complications including stroke and paralysis.* These injuries are thought to occur by a variety of mechanisms.* 2 Injection of particulate steroids into the vertebral artery and its branches during transforaminal, cervical ESIs can cause embolic stroke. Injection into the radiculomedullary arteries that supply the spinal cord during transforaminal, high lumbar, or thoracic ESI can lead to embolic infarction of the spinal cord. In addition, direct needle-associated injury to the spinal cord during ESI has been reported, and it has been postulated that contact between the ESI needle and the vascular supply of the spinal cord may lead to ischemic injury of the cord. The true incidence of these catastrophic neurological complications is unknown due to the lack of the large prospective studies that would provide accurate numerator (all adverse events) and denominator (total epidural injections performed) data. A query of the U.S. Food and Drug Administration's (FDA's) Adverse Events Reporting System covering November 1, 1997 through April 23, 2014, identified 90 cases of serious neurological adverse events associated with ESIs.* However, interpreting these data is challenging as the Adverse Events Reporting System relies on spontaneous reports by healthcare providers and patients, and it is unclear what proportion of all adverse events it is likely to detect. What is clear is that when these complications do occur they can be devastating. The risk of adverse neurological events, particularly those occurring in association with transforaminal injection of particulate steroid formulations, was brought to the attention of the FDA in 2009.* This prompted the FDA to investigate the issue and to subsequently take a number of steps in attempt to mitigate these risks including changing the product labeling for corticosteroids when used for ESI. Last April, the FDA required that a Class Warning be placed on all injectable corticosteroids regarding the risk of neurological complications including spinal cord infarction, paraplegia, quadriplegia, cortical blindness, and stroke. The new label reminded clinicians that the FDA had not evaluate the safety and effectiveness of the epidural injections of steroids and, as such, this use was "off-label."* A second step that the FDA took was to convene a meeting of the Anesthetic and Analgesic Advisory Committee during November 2014 to discuss whether additional regulatory measures or changes to the label were needed. The Committee heard 2 days of presentations from the FDA, outside experts, professional societies, and patients, and there was extensive discussion regarding the risks and benefits of procedure. At the conclusion of the meeting, the Committee voted on the question of whether there are any clinical situations for which a contraindication should be added to

Proceedings of the National Academy of Sciences of the United States of America, Jun 8, 2022

Schwannomas are slow-growing benign neoplasms that develop throughout the body causing pain, sens... more Schwannomas are slow-growing benign neoplasms that develop throughout the body causing pain, sensory/motor dysfunction, and death. Because bacterial immunotherapy has been used in the treatment of some malignant neoplasms, we evaluated attenuated Salmonella typhimurium strains as immunotherapies for benign murine schwannomas. Several bacterial strains were tested, including VNP20009, a highly attenuated strain that was previously shown to be safe in human subjects with advanced malignant neoplasms, and a VNP20009 mutant that was altered in motility and other properties that included adherence and invasion of cultured mammalian cells. VNP20009 controlled tumor growth in two murine schwannoma models and induced changes in cytokine and immune effector cell profiles that were consistent with induction of enhanced innate and adaptive host immune responses compared with controls. Intratumoral (i.t.) injection of S. typhimurium led to tumor cell apoptosis, decreased tumor angiogenesis, and lower growth of the injected schwannoma tumors. Invasive VNP20009 was significantly more efficacious than was a noninvasive derivative in controlling the growth of injected tumors. Bacterial treatment apparently induced systemic antitumor immunity in that the growth of rechallenge schwannomas implanted following primary bacterial treatment was also reduced. Checkpoint programmed death-1 (PD-1) blockade induced by systemic administration of anti–PD-1 antibodies controlled tumor growth to the same degree as i.t. injection of S. typhimurium , and together, these two therapies had an additive effect on suppressing schwannoma growth. These experiments represent validation of a bacterial therapy for a benign neoplasm and support development of S. typhimurium VNP20009, potentially in combination with PD-1 inhibition, as a schwannoma immunotherapy.

Supplementary Methods, Figure Legends 1-5 from miRNA-7 Attenuation in Schwannoma Tumors Stimulate... more Supplementary Methods, Figure Legends 1-5 from miRNA-7 Attenuation in Schwannoma Tumors Stimulates Growth by Upregulating Three Oncogenic Signaling Pathways

Supplementary Figures 1-5 from miRNA-7 Attenuation in Schwannoma Tumors Stimulates Growth by Upre... more Supplementary Figures 1-5 from miRNA-7 Attenuation in Schwannoma Tumors Stimulates Growth by Upregulating Three Oncogenic Signaling Pathways

Encyclopedia of the Neurological Sciences, 2014

Currently, there is substantial room for improvement in the field of pain medicine, particularly ... more Currently, there is substantial room for improvement in the field of pain medicine, particularly with regard to the treatment of chronic pain. The future will likely incorporate multimodal approaches to both diagnostic and therapeutics. These may include genetics, functional imaging, new pharmacotherapeutics, and new interventional approaches.

Anesthesia & Analgesia, 2020

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is a public health crisis of unprece... more BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is a public health crisis of unprecedented proportions that has altered the practice of medicine. The pandemic has required pain clinics to transition from in-person visits to telemedicine, postpone procedures, and cancel face-to-face educational sessions. There are no data on how fellowship programs have adapted. METHODS: A 17-question survey was developed covering topics including changes in education, clinical care, and psychological stress due to the COVID pandemic. The initial survey was hosted by Qualtrics Inc and disseminated by the Association of Pain Program Directors on April 10, 2020, to program directors at Accreditation Council for Graduate Medical Education (ACGME)–accredited fellowships. Results are reported descriptively and stratified by COVID infection rate, which was calculated from Centers for Disease Control and Prevention data on state infections, and census data. RESULTS: Among 107 surveys distribute...

Hearing Research, 2019

Vestibular schwannoma (VS) is the fourth most common intracranial tumor, arising from neoplastic ... more Vestibular schwannoma (VS) is the fourth most common intracranial tumor, arising from neoplastic Schwann cells of the vestibular nerve and often causing debilitating sensorineural hearing loss (SNHL) and tinnitus. Previous research suggests that the abnormal upregulation of inflammatory pathways plays a highly significant, though infrequently described role in VS pathobiology, and that VS-associated SNHL is due not only to mechanical compression of the auditory nerve but also to differences in the intrinsic biology of these tumors. We hypothesize

Molecular Therapy, 2015

CanCer-TargeTed gene and Cell Therapy II a one-step subcutaneous hepatocyte transplantation proce... more CanCer-TargeTed gene and Cell Therapy II a one-step subcutaneous hepatocyte transplantation procedure without a pre-transplant vascularization step such as implanting a FGF-releasing device. The transplanted EHFSs were laminated and formed a vascularized subcutaneous human liver tissues (VSLTs). The VSLTs had liver-specific features such as glycogen stores and albumin, A1AT, and coagulation factor IX syntheses. The aggregated hepatocytes formed several linear structures. Furthermore, subacute hepatic failure model mice (TK-NOG mice) with VSLT were alive at least 7 weeks after liver damage. The present study describes a new approach for vascularized human liver organogenesis under mouse skin. This approach could prove valuable for establishing novel minimally invasive cell therapies for liver diseases.

Pain Medicine, Mar 1, 2014

To describe a case of cervicogenic headache with associated autonomic features and pain in a trig... more To describe a case of cervicogenic headache with associated autonomic features and pain in a trigeminal distribution, all of which responded to third occipital nerve radiofrequency ablation. Single case report. Massachusetts General Hospital Center for Pain Medicine. A 38-year-old woman with history of migraines and motor vehicle accident. Right third occipital nerve diagnostic blocks and radiofrequency lesioning. Pain reduction; physical findings, including periorbital and mandibular facial swelling, tearing, conjunctival injection, and allodynia; and use of opioid and non-opioid pain medicines. The patient had complete relief of her pain and autonomic symptoms, and was able to stop all pain medications following a dedicated third occipital nerve lesioning. This case illustrates the diagnostic and therapeutic complexity of cervicogenic headache and the overlap with other headache types, including trigeminal autonomic cephalgias and migraine. It represents a unique proof of principle in that not only trigeminal nerve pain but also presumed neurogenic inflammation can be relieved by blockade of cervical nociceptive inputs. Further investigation into shared mechanisms of headache pathogenesis is warranted.

International Journal of Molecular Sciences, 2022

Schwannomas are tumors derived from Schwann-lineage cells, cells that protect and support myelina... more Schwannomas are tumors derived from Schwann-lineage cells, cells that protect and support myelinated nerves in the peripheral nervous system. They are typically slow-growing, encapsulated and benign. These tumors develop along peripheral, spinal and cranial nerves causing pain, sensory-motor dysfunction and death. Primary treatment for schwannoma is operative resection which can be associated with significant morbidity. Pharmacotherapy is largely restricted to bevacizumab, which has minimal or no efficacy for many patients and can be associated with treatment-limiting adverse effects. Given the suffering and morbidity associated with schwannoma and the paucity of therapeutic options, there is an urgent need for safe and effective therapies for schwannomas. We previously demonstrated that adeno-associated virus serotype 1 (AAV1) vector mediated delivery of the inflammasome adaptor protein, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) under the...

Pain is a common symptom of diabetic neuropathy. Of the various types of neuropathy, the most com... more Pain is a common symptom of diabetic neuropathy. Of the various types of neuropathy, the most common is distal sensory polyneuropathy (DSPN). DSPN is also the most common cause of pain. Recent studies show that peripheral nerve dysfunction can be the first sign of diabetes and that it even occurs in pre-diabetes (impaired glucose tolerance). Elevated blood glucose and cardiovascular risk factors have been associated with the development of DSPN. The risk and severity of DSPN can be somewhat lessened by tight glucose control. In randomized controlled trials, 4 classes of medications have been proven safe and efficacious to treat pain in DSPN. This issue of Pain Management Rounds reviews the clinical features, methods of diagnosis, and treatment options for diabetic neuropathy. BACKGROUND Over 18 million people in the U.S. ‐ or 6.3% of the population ‐ have diabetes mellitus (DM) and the prevalence continues to increase dramatically across all age groups. 1 Diabetic neuropathy is more...