Check out “What’s New in Research” to find out about discoveries and advancements from our research community. This month, we feature new research from Brigham researchers on physician-nurse collaboration, vitamin D and risk of frailty, growing human kidneys in the lab, preventing blood clots in COVID-19 patients, long-term treatment with a cholesterol-lowering drug, key molecules for corneal differentiation and more.

Study Finds COVID Pandemic May Have Improved Physician-Nurse Collaboration

nurse physician collaboration

Helen Shields

Collaboration between physicians and nurses is vital towards ensuring strong patient outcomes. However, previous studies have suggested differing physician and nurse outlooks toward physician-nurse collaboration. To detect changing attitudes, a recent study conducted by investigators at the Brigham utilized the Jefferson Scale of Attitudes Toward Physician-Nurse Collaboration questionnaire to elicit personal responses from physicians and nurses working at the Brigham, an urban, academic teaching hospital. Their study survey asked a series of questions to measure individual sentiments in the clinical workplace. The authors found through statistical analyses an improved attitude and notable agreement of physicians and nurses on the topic of collaboration. These findings contrast with previous conclusions on the subject, and the study is among the first to demonstrate reliable agreement between physicians and nurses towards collaboration. This could be evidence of a larger, longitudinal transformation in healthcare professional perspectives.

“The COVID-19 pandemic may have shifted people’s attitudes towards meaningful collaboration,” said corresponding author Helen Shields, MD from the Division of Medical Communications and the Division of Gastroenterology, Hepatology, and Endoscopy. “With all of the negative things that have stemmed from the pandemic, this may be at least one positive outcome and hopefully, as a result, signifies a real trend towards better collaboration and better patient care.”

Read more in Advances in Medical Education and Practice.

Vitamin D3 and Omega-3 Fatty Acids Not Helpful in Reducing Risk of Frailty

Brigham investigator

Ariela Orkaby

Frailty is defined as reduced physiological reserve and ability to cope with acute stresses. Up to half of adults over the age of 85 live with frailty and thus, preventative measures are greatly needed. Investigators at the Brigham were interested in examining whether vitamin D3 or marine omega-3 fatty acid supplementation reduced risk of frailty. The researchers analyzed data from the VITamin D and OmegA-3 TriaL (VITAL), a clinical trial of more than 25,000 U.S. adults, also led by investigators from the Brigham. Participants completed questionnaires before the trial began, 6 months after its start, and annually throughout the trial’s five-year duration. Assessment of frailty included measures of physical function, cognition, mood, and general health. The investigators found that neither vitamin D3 nor omega-3-fatty acid supplementation had any effect on frailty scores during the time period. They conclude that these results do not support routine use of vitamin D3 or omega-3 fatty acid supplements for frailty prevention in generally healthy, older adults.

“Our new findings from VITAL are in line with previous results that do not suggest a role of vitamin D3 or omega-3 supplements for most healthy, community dwelling older adults,” said corresponding author Ariela Orkaby, MD, MPH, from the Division of Aging. “We should consider deprescribing unnecessary pills, and instead promoting healthy lifestyle habits. Regular exercise and the Mediterranean diet are proven strategies for prevention of frailty and should be encouraged for all older adults.”

“These new findings from VITAL are an important reminder that dietary supplements are not miracle pills or elixirs of youth,” added JoAnn Manson, MD, DrPH, director of the main VITAL trial and chief of the Division of Preventive Medicine at the Brigham.

Read more in JAMA Network Open.

Key Step Toward Growing Human Kidneys in the Laboratory

Brigham researcher

Joseph Bonventre

Kidney disease affects one in nine adults globally and the incidence of kidney failure is steadily rising around the world.  Being able to grow working kidney tissue in a laboratory could help accelerate medical treatments for kidney disease and restore kidney function. The kidney forms normally in humans as a result of two building blocks– metanephric mesenchyme and ureteric bud. Brigham researchers in the laboratory of Joseph Bonventre, MD, PhD, chief of the Renal Unit and founding chief of the Engineering in Medicine Division, figured out how to generate the first building block– metanephric mesenchyme– resulting in many components of the kidney from human stem cells seven years ago.

The same laboratory has now developed a highly efficient method to generate the second building block (ureteric bud) which matures into the adult kidney collecting system. Further, they demonstrated features

kidney research

Human kidney ureteric bud organoids derived from stem cells; Bonventre Lab

of interaction between the cells of these two building blocks, reproducing aspects of interaction which normally occur when the kidney develops. In addition, for the first time ever, the Bonventre laboratory has developed human cell lines of principal and intercalated cell lines, the two cell lines that make up the last urine processing component of the kidney. This research could help investigators test new therapies for treating kidney diseases that affect the collecting system. These include many congenital abnormalities of the kidney and urinary tract, including polycystic kidney disease one of the most common genetic diseases.

“We have developed a highly efficient way to generate a key component of kidney tissue responsible for maintaining many blood chemistries and critically important for development of the kidney. In addition, we have created, for the first time, human kidney cells that can be used to advance new drugs, aid in investigation of inherited and acquired disorders, and improve our understanding of how the kidney develop and control metabolic balance in the body,” said Bonventre. “Ultimately, with the ability to now generate both components responsible for making functional kidney tissue, this work provides a major step forward in the quest to replace renal function in patients with kidney failure or perhaps, in the future, generate a kidney in a dish.”

Read more in Nature Biotechnology.

Full-Dose Anticoagulation Treatment Prevented Blood Clots in COVID-19 Patients

Brigham researcher

David Berg

A clinical trial of patients with COVID-19 led by investigators at the TIMI Study Group at Brigham and Women’s Hospital and the Critical Care Cardiology Trials Network (CCCTN) has found that full-dose anticoagulation lowers the risk of blood clotting complications compared with standard-dose prophylactic anticoagulation. Brigham researchers presented their findings at a Hot Line session at ESC Congress 2022. Results from previous clinical trials assessing strategies for preventing blood clots in patients with COVID-19 have been mixed. The COVID-PACT trial enrolled critically ill patients with COVID-19 from sites across the U.S. Patients were randomized to receive either full-dose or standard-dose prophylactic anticoagulation therapy. A total of 390 patients were randomized to an anticoagulation strategy. Investigators found that the risk of venous or arterial clotting complications was 44 percent lower among patients who received full-dose compared to standard-dose. Fatal or life-threatening bleeding occurred in four patients in the full-dose group compared to one patient in the standard-dose group.

“Until now, the optimal strategy for preventing blood clots among patients who are critically ill with COVID-19 has remained uncertain,” said David Berg, MD, MPH, of the Division of Cardiovascular Medicine. “COVID-PACT shows that, compared with standard-dose prophylaxis, full-dose anticoagulation more effectively prevents the clotting complications of COVID-19.”

Read more in Circulation.

FOURIER-OLE Trial Finds that Long-Term Use of Evolocumab Further Reduced Cardiovascular Events

Brigham researcher

Michelle O’Donoghue

A clinical trial led by Brigham researchers has found that the long-term use of the cholesterol lowering drug evolocumab was safe, well tolerated, and led to further reductions in the risk of cardiovascular events compared to shorter treatment. Findings from the trial, known as FOURIER open-label extension (OLE), sponsored by Amgen, were presented at a Hot Line session at ESC Congress 2022 by the study’s principal investigator Michelle O’Donoghue, MD, MPH, a senior investigator of the TIMI Study Group in the Division of Cardiovascular Medicine. More than 6,000 participants from the parent trial were enrolled in FOURIER-OLE. During the extension period of the trial, patients received open-label subcutaneous injections of the PCSK9 inhibitor evolocumab regardless of whether they were originally randomized to receive the drug or the placebo. Participants were followed for a median of five years and, therefore, some patients were treated with evolocumab for more than eight years over the course of the parent and extension phase. Those originally randomized to receive evolocumab had a 15 percent lower risk of cardiovascular death, myocardial infarction (MI), stroke, hospitalization for unstable angina or coronary revascularization; a 20 percent lower risk of cardiovascular death, MI or stroke; and a 23 percent lower risk of cardiovascular death during OLE compared to those who were originally randomized to receive the placebo.

“To date, most clinical trials of PCSK9 inhibitors like evolocumab have only looked at its impact over two to three years, but most patients will be on a lipid-lowering therapy for many years,” said O’Donoghue. “Our study has found that long-term use of evolocumab was safe and led to further reductions in cardiovascular events among those who were started on the drug earlier, providing further support for guidelines recommending lipid-lowering therapy with PCSK9 inhibitors.”

Read more in Circulation.

Study Identifies Key Molecule Required for Corneal Differentiation

Brigham researcher

Natasha Frank

The cornea is unique in having high regenerative potential through its stem cells. Loss of stem cells due to injury or disease leads to corneal clouding and blindness. However, the mechanisms that lead to differentiation of corneal epithelial stem cells (also known as limbal stem cells) into clear corneal epithelium are not well understood. To improve the basic science understanding of the molecular pathways and cell subpopulations that give the cornea its regenerative potential, Brigham researchers and their colleagues at Boston Children’s Hospital, and Schepen’s Eye Institute employed a combination of single-cell RNA sequencing of ABCB5-expressing limbal stem cells, flow cytometry, and in situ immunofluorescence methods on corneal cells to analyze their molecular heterogeneity. Through this, they identified Basal Cell Adhesion Molecule (BCAM) as a novel marker for a highly proliferative subpopulation of stem and progenitor cells and discovered its control of corneal differentiation. Further research in this area may prove useful for future medical therapies of corneal disease.

“The cornea — our window to the world — has astounding regenerative properties,” said co-corresponding author Natasha Frank, MD, of the Division of Genetics. “Our study identifies a key population of proliferative cells and a definitive role for BCAM in mediating corneal differentiation.”

Read more in Cell Reports.


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