Finerenone reduces the risk of cardiovascular morbidity and mortality in patients with mild-to-moderate kidney disease and type 2 diabetes. That’s the finding of late breaking research presented in a Hot Line session today at ESC Congress 20211 and published in the New England Journal of Medicine2.
Diabetic kidney disease develops in approximately 40% of patients with diabetes and is the leading cause of chronic kidney disease worldwide.3 Some patients progress to end-stage renal disease, but most die from cardiovascular diseases and infections before needing kidney replacement therapy.3
The FIDELIO-DKD trial previously reported that finerenone, a nonsteroidal mineralocorticoid receptor antagonist (MRA), slowed progression of kidney disease and improved cardiovascular outcomes in patients with predominantly advanced kidney disease and type 2 diabetes.4 FIGARO-DKD investigated cardiovascular and renal outcomes with finerenone treatment in patients with mild-to-moderate kidney disease and type 2 diabetes.
Regarding the study population, FIGARO-DKD enrolled adults with type 2 diabetes and mild-to-moderate kidney disease5 treated with optimised renin-angiotensin system (RAS) blockade. As finerenone increases serum potassium levels by an average of approximately 0.2 mmol/L, patients had to have serum potassium 4.8 mmol/L or below at the run-in and screening visits (but not at randomisation) so that levels could be maintained at an optimal range for most patients, i.e. around 5.0 mmol/L or below. Nevertheless, study drug could be continued up to a potassium level of 5.5 mmol/L. Patients with symptomatic chronic heart failure with reduced ejection fraction were excluded since steroidal MRA treatment is a class 1A recommendation and withholding therapy for the duration of the trial would have been unethical.
A total of 7,437 patients in 48 countries were randomised 1:1 to oral finerenone (10 or 20 mg) or placebo once-daily. The average age was 64.1 years and 69.4% were men. The primary endpoint was a cardiovascular composite of time to cardiovascular death, nonfatal myocardial infarction, nonfatal stroke or hospitalisation for heart failure.
During a median follow-up of 3.4 years, the primary endpoint occurred in 458 (12.4%) and 519 (14.2%) patients in the finerenone and placebo groups, respectively. The relative risk of this endpoint was significantly reduced by 13% with finerenone versus placebo (hazard ratio [HR] 0.87; 95% confidence interval [CI] 0.76-0.98; p=0.03). The observed cardiovascular benefit was largely driven by a 29% reduction in hospitalisation for heart failure.

Researchers at the University of British Columbia’s faculty of medicine and BC Cancer Research Institute have uncovered a weakness in a key enzyme that solid tumour cancer cells rely on to adapt and survive when oxygen levels are low.
The findings, published today in Science Advances, will help researchers develop new treatment strategies to limit the progression of solid cancer tumours, which represent the majority of tumour types that arise in the body.
Solid tumours rely on blood supply to deliver oxygen and nutrients to help them grow. As the tumours advance, these blood vessels are unable to provide oxygen and nutrients to every part of the tumour, which results in areas of low oxygen. Over time, this low-oxygen environment leads to a buildup of acid inside the tumour cells.
To overcome this stress, the cells adapt by unleashing enzymes that neutralize the acidic conditions of their environment, allowing the cells to not only survive, but ultimately become a more aggressive form of tumour capable of spreading to other organs. One of these enzymes is called Carbonic Anhydrase IX (CAIX).
“Cancer cells depend on the CAIX enzyme to survive, which ultimately makes it their ‘Achilles heel.’ By inhibiting its activity, we can effectively stop the cells from growing,” explains the study’s senior author Dr. Shoukat Dedhar, professor in UBC faculty of medicine’s department of biochemistry and molecular biology and distinguished scientist at BC Cancer.
Dr. Dedhar and colleagues previously identified a unique compound, known as SLC-0111 — currently being evaluated in Phase 1 clinical trials — as a powerful inhibitor of the CAIX enzyme. While pre-clinical models of breast, pancreatic and brain cancers have demonstrated the effectiveness of this compound in suppressing tumour growth and spread, other cellular properties diminish its effectiveness.
In this study, the research team, which included Dr. Shawn Chafe, a research associate in Dr. Dedhar’s lab, together with Dr. Franco Vizeacoumar and colleagues from the University of Saskatchewan, set out to examine these cellular properties and identify other weaknesses of the CAIX enzyme using a powerful tool known as a genome-wide synthetic lethal screen.This tool looks at the genetics of a cancer cell and systematically deletes one gene at a time to determine if a cancer cell can be killed by eliminating the CAIX enzyme together with another specific gene.
According to Dr. Dedhar, the results of their examination were surprising and point to an unexpected role of proteins and processes that control a form of cell death called ferroptosis. This form of cell death happens when iron builds up and weakens the tumour’s metabolism and cell membranes.
“We now know that the CAIX enzyme blocks cancer cells from dying as a result of ferroptosis,” says Dr. Dedhar. “Combining inhibitors of CAIX, including SLC-0111, with compounds known to bring about ferroptosis results in catastrophic cell death and debilitates tumor growth.”
There is currently a large international effort underway to identify drugs that can induce ferroptosis. This study is a major step forward in this quest.
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Materials provided by University of British Columbia. Note: Content may be edited for style and length.

Once it has spread (metastasized), uveal (intraocular or eye) melanoma — an unusual form of cancer — has a very high mortality rate. In a study published in Nature Communications, researchers and doctors at the University of Gothenburg and Sahlgrenska University Hospital show that, in a small group of patients with metastatic uveal melanoma, a new combination treatment can bring about tumor shrinkage and prolonged survival.
Uveal melanoma, an infrequent form of malignant melanoma, starts in the pigment cells of not the skin, but the eye. For skin melanoma, immunotherapy using “checkpoint inhibitors” has proved effective in many cases, but this has not applied to intraocular melanoma. Some 80 people get uveal melanoma in Sweden annually, and half of them get metastases, often in the liver. Patients with metastatic uveal melanoma frequently die shortly after diagnosis.
This is a Phase II trial in which 29 patients with metastatic eye melanoma received a combination of two inhibitor drugs that target HDAC (histone deacetylase) and PD-1 (a checkpoint protein on T cells) respectively. In four of these patients, the tumors shrank significantly, and for several patients the course of the disease was slowed down. Unusually, some of the patients are still alive today, three years after the study began.
“Our hope was that the HDAC inhibitor would reprogram hidden cancer cells so that they could be detected by the immune cells, thus making the immunotherapy with PD-1 inhibitors effective,” explains Lars Ny, senior lecturer at the University of Gothenburg and physician specializing in oncology at Sahlgrenska University Hospital.
Resistance with a genetic explanation
“On the whole, the clinical trial met our expectations, although this doesn’t seem to be a curative treatment either. To find out why there were such major differences in how well patients responded, we performed genetic analyses. These showed that the treatment worked better against the tumors where the BAP1 gene was active and intact. This gene is often inactivated in metastases, but now we find that it’s associated with a better response to immunotherapy,” says Jonas Nilsson, professor at Sahlgrenska Academy at the University of Gothenburg, who is active at both the Sahlgrenska Center for Cancer Research and the Harry Perkins Institute of Medical Research in Perth, Australia.

The European Society of Cardiology (ESC) Guidelines on cardiovascular disease prevention in clinical practice are published online today in European Heart Journal.
As much as 90% of the risk of a heart attack, stroke, or peripheral arterial disease (PAD) can be explained by smoking, poor eating habits, lack of physical activity, abdominal obesity, high blood pressure, raised blood lipid levels, diabetes, psychosocial factors, or alcohol. These guidelines focus on atherosclerotic cardiovascular disease (CVD), which affects the arteries. As the inside of the arteries become clogged up by fatty deposits, they can no longer supply enough blood to the body. This process is the main cause of heart attacks, strokes, PAD and sudden death where arteries become completely blocked. The most important way to prevent these conditions is to adopt a healthy lifestyle throughout life, especially not smoking, and to treat risk factors.
Recommendations are provided for healthy adults of all ages, as well as patients with established CVD or diabetes. Identifying who will benefit most from preventive treatments, such as blood pressure and lipid lowering therapies, is central to prevention efforts and therefore the estimation of CVD risk is the cornerstone of the guidelines.
Targets for blood lipids, blood pressure, and glycaemic control in diabetes remain as recommended in recent ESC guidelines on dyslipidaemias, hypertension or diabetes. The current guidelines introduce a stepwise approach to intensifying preventive treatments, while always taking into consideration potential benefit, other conditions, psychosocial factors and patient preferences. In healthy people, for example, the stepwise approach starts with recommendations for everyone: smoking cessation, adopting a healthy lifestyle, and maintaining a systolic blood pressure below 160 mmHg. The recommendations are then tailored according to the 10-year risk of CVD (calculated by a health professional using available risk scores).
“Individualised decisions using risk estimation and a stepwise approach to therapies is more complex than a one-size-fits-all approach, but reflects the diversity of patients and patient characteristics in everyday clinical practice, and is essential to give the right patient the right treatment,” said guidelines task force chairperson Professor Frank Visseren of the University Medical Centre Utrecht, the Netherlands.
A new section is devoted to communication of risk in the shared decision making process. The aims are for individuals to understand their risk, the anticipated risk reduction with preventive actions, the pros and cons of intervention, and their own priorities. In healthy people, the standard approach is to calculate the likelihood of CVD within 10 years. Young people may find estimations of lifetime risk and lifetime benefit of preventive action more informative, since their 10-year risk is generally low.

It takes more than athletic talent to play varsity sports in college, at least for most young people, a new study suggests.
Researchers found that U.S. high-school athletes were much more likely to play sports in college if they came from higher-income families with well-educated parents and attended wealthier schools.
About 14% of 10th grade students whose families were in the top 20% in terms of socioeconomic status played sports in college — compared to fewer than 4% of those in the bottom 20% of socioeconomic status.
Among those who became 12th grade athletes in high school, a marked difference still remained: 23% of the most privileged students played college sports compared to 9% of the least privileged students.
The results contradict the traditional story of how sports often help underprivileged kids succeed in American society, said James Tompsett, co-author of the study and graduate student in sociology at The Ohio State University.
“The idea of sports as a true meritocracy where the best athletes on the field will succeed is largely a myth,” Tompsett said.

In an observational study, Mayo Clinic researchers report that the combination of casirivimab and imdevimab — two monoclonal antibody treatments under Food and Drug Administration emergency use authorization — keep high-risk patients out of the hospital when infected with mild to moderate COVID-19. The findings appear in The Lancet’s EClinicalMedicine.
Nearly 1,400 Mayo Clinic patients were enrolled in the study — 696 who received the drug combo between December 2020 and early April and an equal matched cohort who did not receive it. Their status was evaluated at 14, 21 and 28 days after treatment. At each point, the numbers for hospitalization were significantly lower in the treated group.
At Day 14, 1.3% of the treated group was in the hospital, compared to 3.3% of those who had not been treated. At Day 21, only 1.3% treated was hospitalized, compared to 4.2% of those who had not been treated. At the end of 28 days, 1.6% of those treated was hospitalized versus 4.8% of those who had not been treated. This translated to 60%-70% relative reduction in hospitalization among treated patients. Of those who were subsequently hospitalized, the rates of ICU admission and mortality were low.
“Once again, this real-world study suggests that when patients who are at high risk due to a range of comorbidities contract a mild or moderate case of COVID-19, this combination of monoclonal injections gives them a chance of a nonhospitalized recovery. In other words, they recover safely at home,” says Raymund Razonable, M.D., a Mayo Clinic infectious diseases specialist and senior author of the study.
In a previous Mayo Clinic study published in The Journal of Clinical Investigation findings suggested the use of bamlanivimab reduced hospitalizations in high-risk patients by 40%-60%. That study involved 2,335 treated patients from Mayo Clinic between November of 2020 and February. Comparing their outcomes with 2,335 untreated patients, the ICU admission and mortality rates also were significantly lower with monoclonal antibody treatment. It should be noted that the FDA in April revoked the EUA for bamlanivimab alone and now endorses use of combination monoclonal antibodies.
“Our conclusion overall at this point is that monoclonal antibodies are an important option in treatment to reduce the impact of COVID-19 in high-risk patients,” says Dr. Razonable.
This study was funded and conducted by Mayo Clinic in collaboration with Nference Inc.
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Materials provided by Mayo Clinic. Original written by Robert Nellis. Note: Content may be edited for style and length.

Georgetown University researchers, looking at the ability of people to sound out words after a stroke, found that knowing which region of the brain was impacted by the stroke could have important implications for helping target rehabilitation efforts.
The finding appeared August 30, 2021, in Brain Communications.
“One in five stroke survivors in the United States live with persistent language impairment. Most of these people also struggle with reading,” says the study’s first author, J. Vivian Dickens, PhD, a Georgetown University MD/PhD student conducting research in the university’s Cognitive Recovery Lab and Center for Aphasia Research and Rehabilitation at Georgetown’s Medical Center. “Our study clarifies the neuroanatomical and cognitive bases of post-stroke reading and language deficits, which could help facilitate predictions of deficits in stroke survivors and suggest targeted treatments.”
The research focus was on phonological processing, which is understanding and being able to use the sounds that comprise language. There are three principal aspects to this processing: auditory, or the ability to recognize the sounds of words, such as judging if words rhyme; motor, which is the ability to produce accurate and clear speech; and auditory-motor translation, which is the translation of sounds heard into speech.
“The goal of this study was to understand how post-stroke difficulties with the three different aspects of phonology relate to difficulties with reading,” says Dickens. “There are two broad ways that people read words: one involves sounding out words, which is particularly important for reading new words; the other involves whole-word recognition. People with post-stroke language impairment frequently have specific trouble sounding out words.”
The investigators tested reading and phonological abilities in 67 people, 30 of whom had had a stroke and 37 that had not. Advanced MRI techniques allowed the researchers to trace out white matter connections, which are akin to wiring diagrams for the brain, as well as map out stroke locations in the brains of affected study participants.
“We found two different patterns of reading problems. Strokes involving the left frontal lobe caused problems with motor phonology and one of the two ways of reading, specifically sounding out words. In contrast, strokes involving the left temporal and parietal lobes caused problems with auditory-motor translation and both ways of reading,” says Dickens. “These results may help clinicians develop therapies focused on specific reading problems that individual stroke survivors often struggle with.”
“This study focused on reading aloud single words, a classic measure of reading ability,” says Peter E. Turkeltaub, MD, PhD, director of the Cognitive Recovery Lab in the Center for Brain Plasticity and Recovery, medical director in the Center for Aphasia Research and Rehabilitation and senior author of the article. “Our results are an important step forward in revealing the mechanisms of translating print to sound, which is crucial for developing rehabilitative therapies for patients who have had strokes.”
The investigators are planning studies to help confirm the extent to which these findings can be generalized to silent reading, which relies on the same core psychological processes as oral reading and is more important for reading in daily life. The researchers are also hoping to turn their research tasks into useful clinical tests to diagnose phonological processing.
In addition to Dickens and Turkeltaub, authors of the manuscript at Georgetown include Andrew T. DeMarco, Candace M. van der Stelt, Sarah F. Snider, Elizabeth H. Lacey and Rhonda B. Friedman. John D. Medaglia is affiliated with Drexel University and the University of Pennsylvania, both in Philadelphia.
The authors report no competing interests.
This work was supported by an NIDCD grant #F30DC018215 to Dickens, an NIDCD grant #R01DC014960 to Turkeltaub and U10NS086513 and K12HD093427 grants to DeMarco.

Eating about ½ cup of walnuts every day for two years modestly lowered levels of low-density lipoprotein (LDL) cholesterol, known as “bad cholesterol,” and reduced the number of total LDL particles and small LDL particles in healthy, older adults, according to new research published today in the American Heart Association’s flagship journal Circulation.
Healthy older adults who ate a handful of walnuts (about ½ cup) a day for two years modestly lowered their level of low-density lipoprotein or LDL cholesterol levels. Consuming walnuts daily also reduced the number of LDL particles, a predictor of cardiovascular disease risk.
Walnuts are a rich source of omega-3 fatty acids (alpha-linolenic acid), which have been shown to have a beneficial effect on cardiovascular health.
“Prior studies have shown that nuts in general, and walnuts in particular, are associated with lower rates of heart disease and stroke. One of the reasons is that they lower LDL-cholesterol levels, and now we have another reason: they improve the quality of LDL particles,” said study co-author Emilio Ros, M.D., Ph.D., director of the Lipid Clinic at the Endocrinology and Nutrition Service of the Hospital Clínic of Barcelona in Spain. “LDL particles come in various sizes. Research has shown that small, dense LDL particles are more often associated with atherosclerosis, the plaque or fatty deposits that build up in the arteries. Our study goes beyond LDL cholesterol levels to get a complete picture of all of the lipoproteins and the impact of eating walnuts daily on their potential to improve cardiovascular risk.”
In a sub-study of the Walnuts and Healthy Aging study, a large, two-year randomized controlled trial examining whether walnuts contribute to healthy aging, researchers evaluated if regular walnut consumption, regardless of a person’s diet or where they live, has beneficial effects on lipoproteins.
This study was conducted from May 2012 to May 2016 and involved 708 participants between the ages of 63 and 79 (68% women) who were healthy, independent-living adults residing in Barcelona, Spain, and Loma Linda, California.

A new study shows that two months after the second Pfizer/Moderna vaccination, antibody response decreases 20% in adults with prior cases of COVID-19. The study also tests how well current vaccines resist emerging variants.
The Northwestern University study underscores the importance of receiving a second dose of vaccine, not only because it is commonly known that immunity from vaccines wanes over time, but also because of the risk posed by emerging variants, including the highly contagious delta variant.
The study also showed that prior exposure to SARS-CoV-2 does not guarantee a high level of antibodies, nor does it guarantee a robust antibody response to the first vaccine dose. This directly contradicts the assumption that contracting COVID will naturally make someone immune to re-infection. The findings further support vaccination (and two doses), even for people who have contracted the virus previously.
A team of scientists, including biological anthropologist Thomas McDade and pharmacologist Alexis Demonbreun, tested blood samples from adults who had tested positive for SARS-CoV-2 to measure how long the immunity benefits of Pfizer and Moderna vaccines last and how well they protect from newer variants.
Study participants were selected from a racially and ethnically diverse community-based sample of Chicago-area adults recruited at the start of the pandemic. Using at-home antibody testing kits developed in the lab, participants submitted blood samples two to three weeks after their first and second dose of vaccination and two months after the second dose.
Antibody response after second shot
In the lab, the researchers tested for neutralizing antibodies by measuring whether the blood sample could inhibit the interaction between the virus’ spike protein and the ACE2 receptor — this interaction is how the virus causes an infection once it enters the body.

Staying home and limiting local travel, supporting access to primary care, and limiting contacts in contagion hubs — including hospitals, schools, and workplaces — are strategies that might help reduce COVID-19-related deaths, according to new research. The research team, by statisticians at Penn State, the Sant’Anna School of Advanced Studies in Pisa, Italy, and Université Laval in Quebec, Canada, used novel statistical approaches to compare the first wave of the epidemic across 20 regions in Italy and identify factors that contributed to mortality.
“The first wave of the COVID-19 epidemic took very different paths in different regions, with some areas being hit especially hard while others fared much better,” said Francesca Chiaromonte, leader of the research team, who is a professor of statistics and the holder of the Lloyd and Dorothy Foehr Huck Chair in Statistics for the Life Sciences at Penn State, and the scientific coordinator of the EMbeDS department of excellence at the Sant’Anna School. “We wanted to understand why some regions were hit so much harder than others, so we used both vetted and newly developed techniques in a field of statistics called functional data analysis to compare how the first wave progressed in different regions in Italy.”
Rather than focusing on models for predicting epidemic trajectories, the study used functional data analysis techniques to gather information from the shapes of mortality curves over time, providing a sensitive way to capture associations and patterns from data. The researchers compared mortality curves during the first wave of the epidemic across 20 regions in Italy. After clustering and aligning the curves, to characterize their shapes and account for outbreaks beginning on different dates, the researchers could evaluate factors that might contribute to their differences. Their results appear Aug. 30 in the journal Scientific Reports.
The researchers found that local mobility — how much people moved around their local areas — was strongly associated with COVID mortality. Specifically, they used data from Google’s “grocery and pharmacy” category, which reflects mobility linked to acquiring necessities such as food and medicine. During a national lock-down which started in March 2020, these mobility levels dropped drastically in Italy, roughly by 30% just in the first week of lockdown and then further by as much as 60% during weekdays and almost 100% during weekends in March and April.
“Early on in the epidemic, there were a lot of questions about whether mobility restrictions would really work; our results add to the mounting evidence that they do,” said Chiaromonte. “We see the effect with a lag, but when people reduced their mobility, we saw fewer COVID-related deaths. And we aren’t the only ones to document this, so when we’re told to stay home as a mitigation measure, we should stay home!”
The rates of positive COVID tests and mortality were also associated with each other with a lag, according to the study, reaffirming that positivity is a useful measure to include in disease models.