Check out “What’s New in Research” to find out about discoveries and advancements from Brigham researchers. This month, we feature new research from Brigham researchers on improving quality of cardiovascular patient care without increasing burnout, genome-wide CRISPR screens to detect PARP inhibitor sensitivity and resistance, head coil setups for MR simulations, risk of symptoms and viral rebound after COVID-19, access to complex liver surgery and more.  

Clinician-Owned Practices Enhance Quality of Cardiovascular Patient Care Without Increasing Staff Burnout

Lisa Rotenstein

In a new study, researchers from Brigham and Women’s Hospital identified factors that were associated with primary care practices successfully improving the quality of cardiovascular preventive care without increasing burnout among clinicians and staff. They analyzed 727 small and medium sized primary care practices for improvements in aspirin prescribing, blood pressure control, and smoking cessation counseling as proxies for quality of preventive care. They assessed which of the practices with improvements in quality had decreases or no increase in the percentage of staff reporting burnout over the study period.

They found that across practices of varying size, geography, and composition, 18.3 percent met the criteria to be considered quality and well-being promoting practices. Among all the factors evaluated, they found clinician-owned practices had statistically significant greater odds of improving quality without increasing burnout among clinicians and staff compared to hospitals owned by a health system. Future studies are needed to evaluate more detailed cultural factors that may contribute to these outcomes.

“This study is unique in identifying factors associated with improving both quality of patient care and staff experience,” said first author Lisa S. Rotenstein, MD, MBA, and primary care physician at Brigham. “Our findings add to a growing body of research suggesting positive satisfaction, engagement and utilization outcomes among clinician-owned practices.”

Read more in JAMA Health Forum.

Genome-Wide CRISPR Screens Identify PARP Inhibitor Sensitivity and Resistance in Prostate Cancer

Li Jia

Prostate cancer tumors harboring BRCA1/2 mutations are exceptionally sensitive to PARP inhibitors, while genomic alterations in other DNA damage response (DDR) genes are less responsive. To identify previously unknown genes whose loss has a profound impact on PARP inhibitor response, researchers from Dana-Farber Brigham Cancer Center led a multinational effort to perform genome-wide CRISPR-Cas9 knockout screens. The study goal was to inform the use of PARP inhibitors beyond BRCA1/2-deficient tumors and support reevaluation of current biomarkers for PARP inhibition in prostate cancer.

The study identified multiple novel genes (e.g., MMS22L and RNASEH2B) that are frequently deleted in prostate cancer. These genes could serve as predictive biomarkers for PARP inhibitor response in prostate cancer, according to the study. The research team also found that loss of CHEK2 (the FDA-approved biomarker for therapeutic response to olaparib) confers resistance, rather than sensitivity, to PARP inhibition.

“Current targeted cancer therapies, including PARP inhibitors, are largely guided by mutations of a single gene and overlook concurrent genomic alterations,” said Li Jia, PhD, director of Urology Research, Brigham and Women’s Hospital. “We found that PARP inhibitor sensitivity instead may depend on interaction between multiple genomic alterations. Therefore, comprehensive genomic analysis may help improve clinical decision making.”

Read more in Nature Communications.

Evaluating Image Quality and Patient Comfort in Head Coil Setups for MR Simulations

Evangelia Kaza

Magnetic resonance imaging (MRI) examinations for radiotherapy treatment planning (MR simulations) of brain or head & neck cancer need to be performed in the same immobilization masks worn during radiotherapy. However, these masks don’t fit inside the standard MR coils designed for head/neck imaging. Researchers from Dana-Farber Brigham Cancer Center have modified existing equipment and arranged two flexible UltraFlexLarge18 (UFL18) coils to encompass the immobilization masks. Another option to accommodate the masks relies on the commercial arrangement of two shorter flexible FlexLarge4 (FL4) coils.

The researchers compared the two flexible coil setups for five healthy volunteers and for monthly quality assurance scans of the American College of Radiology (ACR) phantom over two years, forming image quality parameter ratios relative to a diagnostic head/neck coil. Results showed higher signal-to-noise ratio with UFL18 than with FL4 for clinically employed sequences on both phantom and volunteer images. Phantom data of the clinical series additionally demonstrated higher image contrast and uniformity, and less ghosting and tissue heating for UFL18. Moreover, the novel UFL18 configuration was more spacious and perceived by volunteers as less claustrophobic than the commercial FL4 solution. Overall, UFL18 was selected for clinical implementation thanks to its superior image quality and increased volunteer comfort.

“The proposed UFL18 coil arrangement has been successfully used during the last two years at the Radiation Oncology department of Brigham and Women’s Hospital in brain and head & neck MR simulations for radiotherapy treatment planning,” said Evangelia Kaza, PhD, Clinical Physicist Investigator in the Department of Radiation Oncology. “Additional flexible coils can be placed on top of the neck if more inferior coverage is required.”

Read more in the Journal of Applied Clinical Medical Physics.

Among Untreated Patients with COVID-19, Combined Symptom and Viral Rebound is Rare

Jonathan Li

 After completing a course of nirmatrelvir-ritonavir, a treatment for at-risk patients who have contracted COVID-19, some patients have reported worsening symptoms and viral rebound. But does viral rebound and the reemergence of symptoms also occur in patients who are not given this treatment? To further understand this phenomenon, researchers from the Brigham’s Division of Infectious Diseases analyzed the rates of symptom and viral rebound in COVID-19 patients who did not receive nirmatrelvir-ritonavir, in comparison with those who did. The project involved 563 patients who participated in anterior nasal swabs for two weeks and 29 days of symptom tracking in a diary. Symptom tracking focused on the severity of 13 specific symptoms: feeling feverishness, coughing, shortness of breath or difficulty breathing, sore throat, body pain or muscle pain or aches, fatigue, headache, chills, nasal obstruction or congestion, nasal discharge, nausea, vomiting, and diarrhea. Participants self-assessed their symptoms on a scale of zero (absence of symptom) to three (severe symptom) and viral rebound was classified as a symptom scoring at least four points higher than the lowest score after initial improvement. The results showed that symptom rebound was found in 26 percent of participants, viral rebound in 31 percent of participants and high-level viral rebound in 13 percent of participants. However, these results were considered short-term as 89 percent of symptom rebounds and 95 percent of viral rebounds only occurred once before improving long-term. Only three percent of participants experienced both symptom and high-level viral rebound. It is important to note that most participants were unvaccinated and were infected with pre-Omicron COVID-19 variants.

“What these results show is that baseline rates of symptom and viral relapse in those not receiving treatment for COVID-19 need to be accounted for when studying the risk of rebound after antiviral therapy,” said Jonathan Li, MD, of the Brigham’s Division of Infectious Diseases. “In other words, you need a control group of untreated individuals when studying rates of Paxlovid rebound.”

Read more in Annals of Internal Medicine.

Location May Play Role in Likelihood of Patients to Seek Complex Liver Surgery

George Molina

A study led by investigators from Brigham and Women’s Hospital investigated variation within the United States for undergoing liver metastasectomy for colorectal liver metastasis (CRLM). Only half of eligible patients elect to receive this surgery and it was hypothesized that this is due to socioeconomic factors and poverty rates. Using the Surveillance, Epidemiology and End Results Research Plus database, researchers examined those who had a colorectal adenocarcinoma diagnosis between 2010 and 2018, received surgical resection of the primary cancer site and had liver metastasis without extrahepatic metastasis.  Using 11,348 patients from over 194 counties in the U.S., the study concluded that rates of liver metastasectomy were lower in areas with greater poverty. More specifically, the analysis showed that a 10 percent increase in county-level poverty rate resulted in decreased odds of receiving the surgery for CRLM patients. In comparison, undergoing surgery for stage I colorectal cancer (CRC) was not associated with county-level poverty as these findings did not remain the same for patients receiving surgical treatment for stage I CRC.

“Higher poverty at the county-level was associated with lower receipt of liver metastasectomy for U.S. patients with colorectal liver metastasis. However, surgery for a more common and less complex cancer comparator, such as stage I colorectal cancer, was not observed to be associated with county-level poverty rates,” said George Molina, MD, MPH, of the Brigham’s Division of Surgical Oncology . “These findings suggest that access to complex liver surgery for colorectal liver metastasis might be partially influenced by where patients live. Other factors include financial toxicity and lack of trust in the healthcare system and practitioners.”

Read more in JAMA Open Network.

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