New Approach Successfully Reduces Postcesarean Opioid Use

Opioid epidemic, drug abuse and overdose concept with scattered prescription opioids spilling from orange bottle with copy space. Hydrocodone is the generic name for a range of opiate painkillersOral opioids are regularly prescribed in the United States following cesarean delivery. But in the face of the growing opioid epidemic, the wisdom of this practice is under increasing scrutiny.
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At the Forefront of Immunotherapy for Glioblastoma

E. Antonio Chiocca headshotPhysician-investigators in the Department of Neurosurgery at Brigham and Women’s Hospital are leading clinical trials of cutting-edge approaches for treating glioblastoma. Clinical trials are currently underway for patients with recurrent, progressive glioblastoma as well as patients newly diagnosed with high-grade gliomas as investigators pursue new treatment options to stimulate a patient’s immune system to recognize and eliminate cancer in the brain.

A Study of the Treatment of Recurrent Malignant Glioma with rQNestin34.5v.2

In a phase 1 clinical trial led by E. Antonio Chiocca, MD, PhD, chair of the Department of Neurosurgery at the Brigham, investigators are evaluating the investigational drug rQNestin34.5v.2, an oncolytic viral vector engineered from the herpes simplex virus type 1 (HSV1).

The virus has been rendered incapable of making copies of itself outside of glioma cells, and the vector is designed to preferentially infect, replicate and lyse within rapidly dividing tumor cells. Once the tumor cells are lysed, the viral particles they release can infect neighboring tumor cells, continuing the process of cancer cell destruction.

The current study is designed to test the safety of the drug and will also analyze the appropriate dosage as a possible treatment for recurrent or progressive glioblastoma. While several pharmaceutical companies are developing their own oncolytic viruses for targeting various forms of cancer, Chiocca’s team is the first to begin clinical trials in patients with glioblastoma utilizing this particular oncolytic virus. So far, the team has tested this approach in 16 patients with promising results.

“Oncolytic viral vectors are the new frontier of tumor treatment, and we are at the forefront of this trend. We are hoping to see the successes we had in the laboratory translate into marked improvements for our patients with brain tumors,” said Chiocca. “This clinical trial is the culmination of over a decade of research and testing.”

GMCI, Nivolumab, and Radiation Therapy in Treating Patients With Newly Diagnosed High-Grade Gliomas

Enrollment has recently begun for another study led by investigators at Brigham/Dana-Farber Cancer Institute will test the safety of a new combination therapeutic approach to treat patients with newly diagnosed high-grade gliomas. The approach combines the use of an immunostimulator, an immune checkpoint inhibitor and standard of care therapy.

The immunostimulatory approach known as Gene Mediated Cytotoxic Immunotherapy (GMCI) involves the use of aglatimagene besadenovec (AdV-tk) injection into the tumor site and oral valacyclovir to kill tumor cells and stimulate the immune system. Patients undergo tumor resection and receive AdV-tk injection into the wall of the resection cavity. The trial combines GMCI with nivolumab, an immune checkpoint inhibitor that may also stimulate the immune system by blocking the PD-1 immune suppressive pathway. Patients also receive radiation therapy and the chemotherapeutic drug temozolomide.

A Study of Ad-RTS-hIL-12 With Veledimex in Combination With Nivolumab in Subjects With Glioblastoma

In a third clinical trial, investigators will be testing the effectiveness of a gene therapy approach in combination with a checkpoint inhibitor for treating glioblastoma. Patients enrolled in the study will initially receive nivolumab, which is currently FDA-approved to treat other forms of cancer. Patients will undergo craniotomy and tumor resection and, on the day of surgery, will receive a single tumoral injection of Ad-RTS-hIL-12 given with oral veledimex. Ad-RTS-hIL-12 is an inducible vector that encodes interleukin-12, which can activate the immune system in the presence of veledimex. This gene therapy approach, accompanied with low-dose steroids, has been tested in a phase 1 clinical trial and found to have encouraging patient survival, when compared to the historical rate of 5 to 8 months for patients with recurrent glioblastoma. The phase 1 trial combining gene therapy with nivolumab began enrollment this summer and is actively recruiting.

“I’ve had a long-standing interest in immunotherapy and gene therapy. We’ve conducted the research and have studied these therapies in preclinical models, but my interest in moving these treatments into humans is why I am at the Brigham,” said Chiocca. “The strength of research and our close connections with the Dana-Farber Cancer Institute make the Brigham a fertile environment in which to figure out the best approach for patients.”

New Research in Nature: Neoantigen Vaccine for Glioblastoma
Chiocca and other investigators from Brigham and Women’s Hospital and Dana-Farber Cancer Institute recently published in Nature the results from a phase 1/1b trial designed to assess feasibility and safety of a personalized neoantigen vaccine for glioblastoma. The vaccine was extremely safe with no significant side effects. Co-authors from the Brigham Department of Neurosurgery extracted tumor tissue from which the personalized vaccines were developed.
“This personalized approach to creating a vaccine that can reinvigorate a patient’s immune system represents the culmination of a collaboration between experts in neurosurgery and neuro-oncology,” said Chiocca. “We’re thrilled to have played a role in this innovative work.”

Building a Discovery Engine for Genetic Stratification and Precision Treatment of Parkinson’s Disease

microscope image of neuronsVikram (Vik) Khurana, MD, PhD, chief of the Division of Movement Disorders in the Department of Neurology at Brigham and Women’s Hospital, with colleagues and collaborators around the world, is building a research engine poised to deliver therapies that precisely target specific disease mechanisms in individual patients with Parkinson’s disease and related disorders.
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Assessing Older Trauma Patients to Ensure They Get the Specialized Care They Need

Closeup shot of an elderly man holding his wife's hand while she is ill in the hospitalWhen an older person suffers a trauma resulting in multiple broken bones and other injuries, often due to a fall or car accident, ensuring he or she gets appropriate care can be challenging. This is especially true when health care providers don’t have training or experience in geriatrics.
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Brigham Otolaryngologist Takes His Expertise to Haiti

Otolaryngology - Prince - ImageThe expertise of the physicians and surgeons at Brigham and Women’s Hospital benefits patients well beyond New England. Through Partners in Health, the Boston-based nonprofit health care organization, specialists from the Brigham travel to hospitals in developing countries around the globe, offering patient care as well as training for local doctors.
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Can Patients at Low Risk of Surgery Have TAVR?

3D Illustration of Human Heart AnatomyThe PARTNER-3 Continued Access Trial: TAVR in low-risk patients

Brigham and Women’s Hospital is one of two centers in New England currently participating in the PARTNER 3 Continued Access Trial that offers transcatheter aortic valve replacement (TAVR) to low-risk patients undergoing valve replacement for severe aortic stenosis.
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Post-Operative Tracking Saves Lives at the Aortic Disease Center

Echocardiogram to patient in hospitalAll patients who undergo a cardiac procedure at the Aortic Disease Center are placed on a list. After discharge, these patients are systematically followed via a robust post-operative tracking system. Issues that crop up are spotted fast.
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VT Ablation with Investigational Needle Catheter Shows Promise in Patients

catheter ablation computer renderingCatheter ablation has become an important therapy for patients with ventricular tachycardia (VT). However, it has been a challenge to access arrhythmia sources deep within the heart muscle with the use of conventional approaches.
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Guidelines on Perimenopausal Depression Recognize Vulnerable Time in Women’s Lives

women review research posters at the BrighamPerimenopausal mood changes and depression are experienced in some form by about one-fourth of women undergoing the transition to menopause. Yet until recently, there was no formal direction for healthcare providers in identifying and treating this condition. That changed in September 2018, when a panel led by the National Network of Depression Centers with the support of the North American Menopause Society published the first-ever guidelines.
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