Ultrasound device that calms nerves in kidney may offer new treatment for hypertension

 A device that uses ultrasound to calm overactive nerves in the kidneys may be able to help some people get their blood pressure under control.

A new study led by researchers at Columbia University and Université de Paris, France, has found that the device consistently reduced daytime ambulatory blood pressure by an average of 8.5 points among middle-aged people with hypertension.

Doctors usually prescribe lifestyle changes, such as reducing salt intake or losing weight, and medications to lower blood pressure in patients with hypertension. Yet about one-third of hypertensive patients are unable to control their blood pressure despite these interventions.

"Many patients in our clinical practice are just like the patients in our study, with uncontrolled blood pressure in the 150s despite some efforts," says Ajay Kirtane, MD, professor of medicine at Columbia University Vagelos College of Physicians and Surgeons and co-leader of the study.

Leaving blood pressure uncontrolled for too long can lead to heart failure, strokes, heart attacks, and irreversible kidney damage.

"Renal ultrasound could be offered to patients who are unable to get their blood pressure under control after trying lifestyle changes and drug therapy, before these events occur," says Kirtane, who is also an interventional cardiologist and director of cardiac catheterization laboratories at NewYork-Presbyterian/Columbia University Irving Medical Center.

The results of the study, published in JAMA Cardiology, tested the device, which is used in an outpatient procedure called ultrasound renal denervation. The device is still investigational and has not yet been approved by the FDA for use outside of clinical trials.

Kidney nerves and hypertension

Hypertension in middle age is thought to be caused in part by overactive nerves in the kidneys, which trigger water and sodium retention and release hormones that can raise blood pressure. (In older people, hypertension often occurs as blood vessels stiffen). Antihypertensive drugs work in different ways to lower blood pressure, by dilating blood vessels, removing excess fluid, or blocking hormones that raise blood pressure. But none of these medications target the renal nerves directly.

Ultrasound therapy calms overactive nerves in the renal artery, disrupting signals that lead to hypertension. The therapy is delivered to the nerves via a thin catheter that is inserted into a vein in the leg or wrist and threaded to the kidney.

Study results

The new study pooled data from three randomized trials encompassing more than 500 middle-aged patients with varying degrees of hypertension and medication use.

Twice as many patients who received the ultrasound therapy reached their target daytime blood pressure (less than 135/85 mmHg) compared to patients in the sham groups.

"The result was almost identical across the different study groups, which definitively shows that the device can lower blood pressure in a broad range of patients," Kirtane says.

The procedure was well-tolerated, and most patients were discharged from the hospital the same day. According to Kirtane, improvements in blood pressure were seen as soon as one month after the procedure.

The treatment will be evaluated by the FDA in the coming months.

Bottom line for patients with resistant hypertension

The investigators expect the treatment could be offered as an adjunct to medication therapy and lifestyle changes for patients with uncontrolled hypertension.

"Once the device is available, we envision recommending it to patients who have tried other therapies first. The hope is that by controlling blood pressure, we might be able to prevent kidney damage and other effects of uncontrolled blood pressure," Kirtane adds.

The study, titled "Patient-Level Pooled Analysis of Ultrasound Renal Denervation in the Sham-Controlled RADIANCE II, RADIANCE-HTN SOLO and RADIANCE-HTN TRIO Trials," was published on February 28 in JAMA Cardiology. The study includes data from the RADIANCE II trial, which was published simultaneously in JAMA and was also co-led by Kirtane.

More information: Patient-Level Pooled Analysis of Ultrasound Renal Denervation in the Sham-Controlled RADIANCE II, RADIANCE-HTN SOLO and RADIANCE-HTN TRIO Trials, JAMA Cardiology (2023). DOI: 10.1001/jamacardio.2023.0338

https://medicalxpress.com/news/2023-02-ultrasound-device-calms-nerves-kidney.html

Behavior change program linked to 20% reduction in risk of diabetes

 An NHS behavior-change program has been linked to a significant reduction in the risk of developing type 2 diabetes mellitus in adults with raised blood sugars.

The analysis, carried out by University of Manchester researchers shows that when controlling for the characteristics of participants, the risk of diabetes progression was 20% lower in people with pre-diabetes referred to the NHS Diabetes Prevention Program (NDPP) when compared to similar patients not referred to NDPP.

The study is published today (Feb. 28) in the journal PLoS Medicine.

The NHS Healthier You Diabetes Prevention Program in England is offered to non-diabetic adults with raised blood sugars—or pre-diabetes—providing exercise and dietary advice to help reduce people's risk of developing the disease.

Across the 2,209 GP practices for which the researchers had data, more than 700,000 people were identified with pre-diabetes and about 100,000 had a code in their health records indicating they were referred to the program.

18,470 patients referred to NDPP were matched to 51,331 similar patients not referred to NDPP.

The probability of converting to type 2 diabetes at 36 months after referral was 12.7% for those referred to the NDPP and 15.4% for those not referred to the NDPP.

Using a figure of 1,000 people referred to NDPP and 1,000 not referred to NDPP, by 36 months after referral, the team calculate they would expect 127 conversions to type 2 diabetes in the group referred to the program and 154 in the group not referred.

The mechanism for the difference is likely to be through weight reduction, with previous work showing that people who attended the NHS DPP were associated with a significant reduction in weight—the key factor in reducing risk—of 2.3 kg on average.

In addition, prior work also showed levels of HbA1c—the average blood sugar levels for the previous two to three months—reduced by a significant 1.26 mmol/mol.

Most of the previous trial results have shown that weight loss is the key factor in reducing risk of the disease; increased BMI was also a key factor.

Dr. Rathi Ravindrarajah from The University of Manchester said, "Our findings show that the NDPP appears to be successful in reducing the progression from non-diabetic hyperglycemia to type 2 diabetes.

"Even though we were only able to examine referral to the program, rather than attendance or completion, it still showed a significant reduction in risk of 20%.

"That suggests the decision to implement program quickly and at scale in England was the right one.

"And as the results are reproducible, it also supports the continuation of similar programs to Northern Ireland, Scotland and Wales."

Professor Evangelos Kontopantelis from The University Manchester said, "Type 2 diabetes is a major public health concern which has been rising globally, with over 3 million people in the U.K. currently diagnosed with it.

"Previous studies have shown that both lifestyle modifications through diet and physical activity and medication can prevent progression to this condition.

"This study is good news for the Healthier You Diabetes Prevention Program which we show beyond doubt is a powerful way to protect your health."

Health and Social Care Secretary Steve Barclay said, "The NHS Diabetes Prevention Program has seen promising results with a 20% reduction of risk to those taking part developing type 2 diabetes, empowering people suffering with pre-diabetes to take control of their own health.

"Type 2 diabetes costs the NHS around £10 billion a year, but this evidence-based program is an example of how we can help people make lifestyle changes to prevent the disease progressing, while ensuring value for the taxpayer."

NHS national clinical director for diabetes and obesity, Professor Jonathan Valabhji, said, "This important study is further evidence that the NHS is preventing type 2 diabetes and helping hundreds of thousands of people across England to lead healthier lives.

"We completed roll out of the NHS Diabetes Prevention Program in 2018, and now over 1.2m people have been offered support with lifestyle changes including better quality nutrition, weight loss, and increased physical activity, which this study shows is preventing development of this life-changing condition."

More information: PLoS Medicine (2023). www.fundingawards.nihr.ac.uk/award/16/48/07

https://medicalxpress.com/news/2023-02-behavior-linked-reduction-diabetes.html

Identifying the inflammatory cells behind chemo brain

 Immune cells that keep the brain free of debris but also contribute to inflammation are the likely culprits behind the concentration and memory problems that sometimes follow one type of chemotherapy, a new study in mice suggests.

Researchers previously showed (in work published in Scientific Reports ) that female mice given paclitaxel, a drug commonly used to treat breast, ovarian and other cancers, developed memory problems that were linked to inflammation in the brain. Mice receiving a placebo did not develop the "mental fog" phenomenon known as chemo brain.

In this study, the team used a technique to delete immune cells called microglia from the brains of mice that had received paclitaxel. The loss of those cells restored the chemo-treated animals' memory and also lowered inflammation in their brains.

"That was the peak of the paper: We demonstrated that microglia were necessary for the cognitive impairments we've seen with paclitaxel—the behavior was reversed," said senior author Leah Pyter, an investigator in the Institute for Behavioral Medicine Research at The Ohio State University.

"When we got rid of those microglia, it was associated with a reduction in the inflammatory response to chemo," said Pyter, associate professor of psychiatry and behavioral health in Ohio State's College of Medicine. "So we think that when microglia are activated and become pro-inflammatory, that's what is ultimately affecting neurons to impair memory."

The research was published online recently in the journal Brain, Behavior and Immunity.

In these studies, the mice never have cancer—the research is intended to study only the effects of paclitaxel, which is often combined with one or more additional drugs in regimens determined to provide the most effective treatment for certain types of breast cancer. A member of the Cancer Control Research Program, Pyter is also studying how the gut microbiome may play a role in chemo brain.

Identifying chemotherapy side effects, and the cells and pathways involved, in animal studies is a first step toward proposing potential interventions that could lessen the impact this important cancer treatment has on the body and brain. Chemotherapy agents work by killing cancer cells, but also kill other dividing cells, and the immune system clean-up of resulting debris is thought to drive inflammation, Pyter said.

The team predicts that inflammatory cells in the rest of the body, known as the periphery, are sending signals that activate microglia to become pro-inflammatory in the brain, and those signals interact with cells in the blood-brain barrier—hinting at three potential areas to target.

"We should always be trying to get to more targeted treatments. And the first step of that is to understand who the major players are," Pyter said. "As we look for potential targets for intervention, we have to keep in mind that cancer patients need their peripheral immune systems intact to respond to tumor cells and get rid of them. So it's tricky."

In the new study, mice were given six cycles of paclitaxel injections or a placebo. Researchers found that both microglia and astrocytes, cells in the brain that have an immune role but also perform numerous functions to keep neurons healthy, were activated by the chemotherapy in the hippocampus, the region of focus in this work.

Machine learning analysis showed that compared to mice that received a placebo, microglia in the brains of mice receiving chemo were producing more pro-inflammatory proteins and suppressing a protein important for cognition-related neuron health.

An experimental drug that inhibits a substance that microglia in mice need for survival was added to the animals' food to deplete microglia in their brains. Chemo-treated mice with normal brain immune cell levels showed memory problems in a standard lab test. In contrast, memory in the mice with depleted microglia was restored, and chemo-induced pro-inflammatory proteins in their brains were significantly reduced.

Drugs similar to this experimental compound have been used in cancer patients receiving paclitaxel to target other types of immune cells, which suggests that temporarily clearing away microglia in humans may be feasible, Pyter said.

"We know that chemotherapy is lifesaving, but comes with the potential for toxicity. A better understanding of how chemotherapy affects the brain opens up research areas and interventions to improve the lives of our cancer patients," said Dr. Peter Shields, deputy director of The Ohio State University Comprehensive Cancer Center and a practicing thoracic oncologist at The James Cancer Hospital and Solove Research Institute.

Pyter also said the findings hint at possible long-term cognitive effects from paclitaxel because microglia are unusual among immune cell types: They have a long life and don't repopulate frequently.

"Microglia are always there—they're very dynamic and they're trolling for issues. They might look completely normal until they're activated, and then their response to that activation can be very abnormal," she said. "We're using chemo as a hypothesized way to activate them. But say a cancer patient receives and finishes chemo. But later, they have surgery or a huge stressor in their life—that will reactivate those cells and they might respond oddly later in life."

"This model doesn't mimic long-term side effects. But it is a big concern because many breast cancer patients survive, and the side effects don't always go away."

More information: Corena V. Grant et al, Microglia are implicated in the development of paclitaxel chemotherapy-associated cognitive impairment in female mice, Brain, Behavior, and Immunity (2022). DOI: 10.1016/j.bbi.2022.12.004

https://medicalxpress.com/news/2023-02-inflammatory-cells-chemo-brain.html

Alternative bladder cancer treatment emerges amid worldwide shortage of standard of care BCG

 An on-going, worldwide shortage of bacillus Calmette-Guérin (BCG) means that many patients with a common and serious type of bladder cancer have limited access to this effective standard of care treatment. But for the first time in almost 50 years, there appears to be a viable treatment alternative.

A new study from the University of Iowa finds that a safe, inexpensive combo-chemotherapy is better tolerated than BCG and is better at preventing high-grade cancer recurrence in patients with non-muscle invasive bladder cancer (NMIBC).

Bladder cancer is the sixth most common cancer in the U.S., and NMIBC accounts for about 75% of bladder cancer cases. High-risk NMIBC has a significant risk of both recurrence and progression. Typical treatment for high-risk NMIBC involves surgical removal of the tumor followed by treatment with BCG.

The new approach, which was developed by Michael O'Donnell, MD, at the University of Iowa over 10 years ago, replaces BCG with a combination of two inexpensive, readily available chemotherapy drugs—gemcitabine and docetaxel (gem/doce). Based on this pioneering research from the UI, other major cancer centers have increasingly adopted this regimen, as well. Most recently, a UI study published in 2022 showed that 82% of patients with high-risk NMIBC who were treated with gem/doce instead of BCG remained cancer-free two years after treatment.

"With that earlier study we showed that patients with untreated non-muscle invasive bladder cancer who received gem/doce had excellent safety and efficacy outcomes that were on par with historical outcomes of BCG," says Vignesh Packiam, MD, clinical assistant professor of urology with UI Health Care.

"This was novel and impactful as it provides the first highly effective and accessible alternative to BCG, for which none previously existed. However, one limitation in that study was there was no direct comparison to the standard of care treatment—BCG."

With the new study, published Feb. 28 in JAMA Network Open, Packiam, O'Donnell and their UI colleagues address that limitation by retrospectively comparing outcomes of 312 patients who received either gem/doce or BCG over a 10-year period at UI Hospitals & Clinics.

The study found that gem/doce provided better recurrence-free survival in patients with high-risk NMIBC compared to BCG, and fewer patients who received gem/doce therapy discontinued their treatment compared to patients who received BCG.

"The results were very promising," says Packiam, who also is a member of UI Holden Comprehensive Cancer Center. "We believe this new study will have an immediate impact as it shows stronger evidence for using gem/doce for patients with newly diagnosed non-muscle invasive bladder cancer, for whom there is no alternative option due to the BCG shortage."

In addition to Packiam and O'Donnell, the UI team included first author Ian McElree, a medical student at the UI Carver College of Medicine, as well as Ryan L. Steinberg, MD, and Sarah Mott.

More information: Ian M. McElree et al, Comparison of Sequential Intravesical Gemcitabine and Docetaxel vs Bacillus Calmette-Guérin for the Treatment of Patients With High-Risk Non–Muscle-Invasive Bladder Cancer, JAMA Network Open (2023). DOI: 10.1001/jamanetworkopen.2023.0849

https://medicalxpress.com/news/2023-02-alternative-bladder-cancer-treatment-emerges.html

Possible way to prevent or treat lung damage associated with long COVID

 A team of medical researchers at Stanford University, working with a colleague from the Institute of Biomedical Sciences in Taiwan, has discovered a possible way to prevent or treat lung damage associated with long COVID. In their study, published in Proceedings of the National Academy of Sciences, the group isolated genes associated with inciting an inflammatory overreaction to a COVID-19 infection in the lungs and turned them off in test mice to prevent lung damage.

The global pandemic has proven to be uniquely challenging; from efforts to stop its spread to the development of therapeutics and vaccines and the advent of anti-vaxxers combating scientific advances, the SARS-CoV-2 virus has shown itself to be a formidable adversary. And while the amount of attention given to the pandemic has dwindled, the virus has still not gone away. And neither has its ability to leave some victims with long-lasting, sometimes permanent physical damage.

Called long COVID, the damage wrought by the virus can occur in a variety of organs, including the brain, the heart and the lungs. In this new effort, the team in California noted that more than 200 people have undergone lung transplants due to the damage done by a COVID-19 infection. Suspecting that it might have a genetic basis, the group undertook a sequencing study comparing such patients with others who had no such damage.

In their study, the research team found that the lung damage caused by a COVID infection was actually caused by an overreaction of the immune system to the virus and resulting inflammation. To test the possibility of averting such an overreaction, the team transplanted human lung organoids into test mice and infected them with an engineered version of the SARS-CoV-2 virus. This led to the kind of damage seen in human patients with standard COVID infections. They then gave the test mice antibodies designed to block the genes in their lungs that were associated with overreaction to virus exposure and the associated inflammation. Four weeks later, tests showed that the treatment led to reductions in fibroids and lung tissue that had returned to normal.

The team notes that more testing is required, but suggest that their approach could represent a potential therapeutic approach to preventing and treating lung damage in patients due to long COVID.

More information: Lu Cui et al, Innate immune cell activation causes lung fibrosis in a humanized model of long COVID, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2217199120

https://medicalxpress.com/news/2023-02-lung-covid.html

US companies rush to issue corporate debt, busiest February ever

 U.S. companies with the highest credit ratings sold a record $144 billion of debt securities so far in February to get ahead of further potential interest rate hikes, meeting strong demand from investors looking to capitalize on a spike in yields.

Investment-grade rated corporate bond issuance in February has been the busiest ever for the month with the tally as of Monday already some $20 billion ahead of the now second-heaviest February in 2021, said BMO Capital Markets' fixed income strategy director Dan Krieter in a report.

Companies have been rushing to issue bonds as yields spiked to touch new highs with the Federal Reserve looking to keep interest rates higher for longer.

Traders now expect the Fed to raise rates to about 5.4% in July, with only a minor decline by December, futures markets show. In early February, the market envisaged rates rising to a peak under 5.0%, with several rate cuts by year's end.

The average yield on U.S. investment grade bonds rose to 5.55% on Monday from just 4.94% on Feb. 1..

"There's much more yield now to be had in corporates," said David del Vecchio, co-head of the U.S. investment grade corporate bond team at PGIM Fixed Income.

February's bonds were oversubscribed by 3.64 times on average, data from Informa Global Markets said.

Investors still had plenty of cash, despite the flurry of issuance, said Blair Shwedo, head of IG corporate bond trading at U.S. Bank.

Analysts expect $160-165 billion of new bond supply in March.

"With more volatility, you may see some short term negative returns but overall, we’re well positioned to have a very nice positive total return in investment grade credit in 2023," said Natalie Trevithick, head of investment grade credit strategy at investment management firm Payden & Rygel.

https://www.yahoo.com/now/us-companies-rush-issue-corporate-184900409.html

Microsoft adds new Bing to Windows computers in effort to roll out AI

 Microsoft Corp on Tuesday started adding its recently upgraded Bing search engine to its Windows computer software, aiming to put artificial intelligence (AI) at the fingertips of hundreds of millions of people.

The Windows 11 update, Microsoft's latest in a flurry of product revamps this month, shows how the Redmond, Washington-based software maker is marching ahead on AI notwithstanding recent scrutiny of its technology.

Microsoft's operating system will include the new Bing in desktop computers' search box, which helps half a billion monthly users navigate their files and the internet, the company said. The search engine itself is still in a preview mode, accessible to more than 1 million people in 169 countries with a wait list for others, Microsoft said.

The company unveiled its AI-powered chatbot for Bing as it aims to wrest market share from Alphabet Inc's Google, moving faster with ChatGPT-like software for search.

Microsoft has been gathering feedback on the new Bing before a wider rollout. The engine's AI chatbot reportedly professed love or made threats to some testers, leading the company to cap long chats it said "provoked" responses it did not intend.

In addition to the new Bing, Microsoft's Windows update will include software that can connect to iPhone messages and calls starting with a limited set of users, the company said.

https://www.yahoo.com/now/microsoft-adds-bing-windows-computers-140729547.html