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The exclusion of pregnant patients in initial COVID-19 vaccine clinical trials left many patients and doctors wondering how the vaccine might affect pregnant patients and their unborn babies. A new Northwestern Medicine study has found the vaccine is not associated with birth defects that are detectable on ultrasound.
“This is yet another important piece of data that helps bridge the chasm that was left when pregnant individuals were excluded from those initial vaccine trials,” said corresponding author Dr. Emily Miller, chief of obstetrics at Northwestern Medicine and assistant professor of maternal fetal medicine at Northwestern University Feinberg School of Medicine.
The study will be published April 4 in the journal JAMA Pediatrics.
“One of the reasons women struggle with the vaccine in pregnancy is they’re worried about their babies and don’t want to take any risks,” said first author Dr. Rachel Ruderman, a fourth-year resident in obstetrics and gynecology at Feinberg. “This study shows there really is no increased risk of birth defects, and it supports other evidence that shows the vaccine is safe and beneficial for mom and baby.”
Study analyzed for a wide range of birth defects
The types of birth defects the scientists were looking for on the study participants’ ultrasounds were ones they deemed “major fetal structural anomalies,” such as the baby’s heart not forming correctly or the spine not closing properly. In the United States, 3 to 5% of births are impacted by these types of defects, resulting in increases in infant morbidity, mortality and billions of dollars in cost.

The rules to the kids’ game “red light, green light” are easy to follow: red always means stop, and green always means go. But now, researchers from Japan have found that a key protein involved in B cell signaling acts as both a red light to signaling in healthy cells and a green light to signaling in immune-deficient cells.
In a study published in March in Science Signaling, researchers from Tokyo Medical and Dental University (TMDU) have revealed that CD22, a crucial molecule in B cell signaling, switches from an inhibitory role to an activating role when B cell receptor (BCR) signaling is compromised due to a genetic defect that causes an immune disorder.
Contact between BCRs and foreign invaders prompts B cells to make antibodies, and CD22 inhibits BCR signaling to keep B cells from inappropriately releasing antibodies. Interestingly, previous research suggests that this inhibition is regulated by binding of CD22 to other factors expressed on the same cell. In contrast, a protein called CD45 is a main activator of BCR signaling, and defects in the gene encoding CD45 cause an immunodeficiency syndrome.
“CD45 normally enhances BCR signaling,” explains Chizuru Akatsu, lead author on the study. “When CD45 is missing in laboratory cell lines, BCR signaling is dramatically decreased; however, signaling is not affected as severely in mice when CD45 is missing, which suggests that there is some kind of compensatory mechanism at work.”
To investigate the relationship between CD22 and BCR signaling restoration in the absence of CD45, the researchers disrupted the binding of all interaction partners of CD22 either continuously or for a short time and looked at the effect this had on BCR signaling.
“The results were entirely unexpected,” says Takeshi Tsubata, senior author. “Acute disruption of binding between CD22 and its ligands did not affect the restoration of BCR signaling in B cells lacking CD45, whereas continuous disruption of this binding resulted in markedly less BCR signaling recovery.”
As it turns out, the cells in which signaling was restored expressed unusually high levels of BCR, which accounted for their ability to continue functioning relatively normally. BCR signaling occurs at low levels even in the absence of stimulation by foreign antigens, and this low-level steady-state signaling is required for B cell development and survival. Because BCR is an endogenous ligand of CD22, continuous CD22 binding to its ligands facilitates inhibition of steady-state BCR signaling by CD22. If BCR signaling is compromised by a defect such as CD45 deficiency, steady-state signaling is markedly reduced by the signaling defect together with the signal inhibition by CD22; therefore, only B cells that express high levels of BCR survive. Through this mechanism, CD22 paradoxically restores BCR signaling in immune-deficient B cells.
“What is really interesting about this result is that it could point toward a way to restore immune function in patients with immune disorders involving B cell signaling deficiencies,” states Akatsu.
Given that B cells and immunoglobulins are present — though in greatly reduced numbers — in immunodeficient patients with defects in BCR signaling, CD22 may be a useful treatment target. Activating CD22 could help restore B cell function in patients with B cell signaling deficiencies such as X-linked agammaglobulinemia.
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Supporting actors sometimes steal the show. In a new study published today in Cell, researchers headed by Prof. Ido Amit at the Weizmann Institute of Science have shown that supporting cells called fibroblasts, long viewed as uniform background players, are in fact extremely varied and vital. A subset of these cells, according to the study, may lie at the origins of scleroderma – a rare autoimmune disease. The findings open a new direction for developing a future therapy against this devastating, incurable disorder.  Scleroderma (from the Greek skleros, meaning “hard,” and derma, meaning “skin”) is characterized by the formation of an abnormally hard, inflexible layer of skin on the arms, legs and face. Its manifestations vary greatly among patients. In about a third of the cases, the disease, which mainly strikes women aged 30 to 50, advances rapidly and spreads beyond the extremities, causing life-threatening damage to internal organs. Immune-regulating drugs that normally bring relief to people with autoimmune diseases are less effective in scleroderma, which has a higher mortality rate than other rheumatic disorders.“Scleroderma is one of the most frustrating disorders to treat – we can alleviate some of the patient’s symptoms, but usually we cannot significantly affect the cause of the disease, block its progression or reverse its course,” says Prof. Chamutal Gur, a senior physician in the Rheumatology Department at Hadassah University Medical Center, who led the new study in Amit’s lab in Weizmann’s Immunology Department. Her interest in this disease is not only professional: Two of her cousins have been diagnosed with scleroderma. When she joined Amit’s lab as a postdoctoral fellow some three years ago, her goal was to get to the root of this puzzling disease.Gur and colleagues launched a study of scleroderma using technologies developed in Amit’s lab for simultaneously exploring the genetic material of thousands of individual cells. These technologies, known as single-cell RNA sequencing, reveal each cell’s unique identity. The study was conducted in collaboration with Dr. Hagit Peleg, Dr. Suhail Aamar, Dr. Fadi Kharouf, Dr. Anat Elazary and other rheumatologists at Hadassah University Medical Center, and with Prof. Alexandra Balbir-Gurman, who supervised the clinical aspect of the study, and Dr. Yolanda Braun-Moscovici, both of the Rambam Health Care Campus.The researchers collected skin samples from nearly 100 scleroderma patients and from more than 50 healthy volunteers who served as a control group, in the largest-ever study of this kind to explore the disease. While perfecting the sample collection technique, Gur performed nearly 20 skin biopsies on herself.As scleroderma is considered an autoimmune disorder – that is, one in which the immune system attacks the person’s own body – the researchers looked for immune cell differences between the control and patient groups. But contrary to what would be expected of an autoimmune disease, the analysis failed to reveal a characteristic, global pattern of immune abnormalities in most of the patients. Instead, to their surprise, the researchers found it were the patients’ fibroblasts that differed significantly from those of the controls.Aside from roles in growth and wound healing, fibroblasts were thought to be mere “scaffolding” holding cells in place. The new study challenges this humdrum picture: The researchers found that fibroblasts can be divided into about ten major groups, each performing different and often vital functions, from conveying immune system signals to affecting metabolism, blood clotting and blood vessel formation. These groups can be further broken into some 200 subtypes.Most importantly, the researchers managed to identify a subset of fibroblast whose concentration drops sharply in the early stages of scleroderma. They named these cells Scleroderma-Associated Fibroblasts, abbreviated as ScAFs (which is also short for “scaffold”). Whereas in healthy controls ScAFs accounted for nearly 30 percent of all fibroblasts, this percentage decreased dramatically in scleroderma patients and continued to plummet as the disease progressed.The researchers mapped out the locations of ScAFs deep within skin tissue, and they tapped these cells’ RNA to determine what changes a functional ScAF into a malfunctioning cell common in scleroderma patients. They also identified biological markers correlated with specific kinds of organ damage; these markers can help physicians administer a personalized treatment, in order to prevent life-threatening complications. The research also revealed ScAF-related signaling pathways that can be targeted in future scleroderma therapies.“The reduction in the size of a critical subset of fibroblasts appears to be an early event in the course of scleroderma,” Amit says. “It might be possible to design a therapy that will make up for this loss, slowing the progression of the disease.”“Our approach is relevant to other diseases,” adds Dr. Shuang-Yin Wang of Amit’s lab, who led the study’s data analysis using artificial intelligence tools. “It reveals the enormous potential of meticulous tissue analysis involving advanced single-cell technologies for uncovering disease dynamics.”“Integrating the latest single-cell genomic research techniques with clinical data can shed new light on diseases whose origins are currently obscure,” Amit concludes.Study participants included Fadi Sheban, Mor Zada, Dr. Baoguo Li, Adam Jelinski, Dr. Daniel Kirschenbaum, Dr. Diego Adhemar Jaitin, Dr. Bjørt K. Kragesteen, Dr. Chamutal Bornstein, Shir Shlomi-Loubaton, Eyal David, Oren Barboy, Dr. Adi Moshe, Dr. Assaf Weiner and Dr. Amir Giladi of Weizmann’s Immunology Department; Dr. Tehila Tzemach, Prof. Yaakov Naparstek, Dr. Batia Avni, Dr. Sigal Grisariu, Dr. Rony Shreberk-Hassidim, Dr. Vered Molho-Pessach, Dr. Dalit Amar, Dr. Tomer Tzur, Dr. Rottem Kuint, Dr. Moshe Gross and Dr. Shlomit Erenfeld of Hadassah University Medical Center; Dr. Tomer Meir Salame, Dr. Efrat Hagai and Dr. Yoseph Addadi of Weizmann’s Life Sciences Core Facilities Department; Dr. Liat Fellus-Alyagor and Dana Hirsch of Weizmann’s Veterinary Resources Department; Dr. Moshe Biton of Weizmann’s Biological Regulation Department; and Dr. Reut Tzemach of Weizmann’s Immunology Department and the Tel Aviv Sourasky Medical Center – Ichilov.Prof. Amit’s research is supported by the Dwek Institute for Cancer Therapy Research; the Moross Integrated Cancer Center; the Belle S. and Irving E. Meller Center for the Biology of Aging; the Morris Kahn Institute for Human Immunology; the Thompson Family Foundation Alzheimer’s Disease Research Fund; the Adelis Foundation; the Elsie and Marvin Dekelboum Family Foundation; the Richard & Jacqui Scheinberg and Garvan Weizmann Partnership Donors; the Ben B. and Joyce E. Eisenberg Foundation; the Wolfson Family Charitable Trust & Wolfson Foundation; the Vainboim Family; Miel de Botton; and the European Research Council. Prof. Amit is the incumbent of the Eden and Steven Romick Professorial Chair.

People with heart failure who received an annual flu shot had lower rates of pneumonia and hospitalization on a year-round basis and a reduction in major cardiovascular events during peak flu season, in a study presented at the American College of Cardiology’s 71st Annual Scientific Session. However, the trial did not meet its primary endpoint as patients who received the flu vaccine showed no significant reduction in rates of major cardiovascular events on a year-round basis during the study’s three-year follow-up period.
The study is the first randomized controlled trial to assess the benefits of the flu vaccine specifically in people with heart failure, who face a high risk of cardiovascular events. It was conducted in countries across Asia, Africa and the Middle East where getting a flu shot is not routine for most people. The trial did not meet its primary or co-primary endpoints, which focused on the rate of major cardiovascular events analyzed on a year-round basis. A prespecified sub-analysis of the data revealed that people who received a flu shot showed a significant reduction in cardiovascular events during periods of the year when rates of influenza were highest.
“Although our prespecified endpoints were not significant, our data suggest that there’s a clinical benefit [to getting a flu shot] given the clear reduction in pneumonia, moderate reduction in hospitalization and reduction in vascular events and deaths during periods of peak influenza,” said Mark Loeb, MD, Michael G. DeGroote chair in infectious diseases at McMaster University in Ontario, Canada, and the study’s lead author. “When taken together with previous trials and observational studies, the collective data demonstrate there is a substantial benefit to receiving a flu vaccine for people with heart failure.”
Heart failure is a condition in which the heart becomes too weak or stiff to pump blood effectively. Previous studies have shown that people with heart disease or cardiovascular risk factors face an elevated risk of complications when they contract influenza, but there has been a lack of evidence on whether flu vaccines can help to mitigate this risk specifically in people with heart failure.
The trial enrolled 5,129 patients with heart failure in 10 countries where flu vaccines are not common. Participants did not routinely get flu shots and had previously received a flu shot no more than once during the three years preceding the trial. Participants were randomly assigned to receive a flu shot or a placebo annually for up to three years, though they were also allowed to get a flu shot outside of the trial. Researchers tracked health outcomes for a median of 2.9 years. The trial’s primary endpoint was a composite of death from cardiovascular causes, non-fatal heart attack or non-fatal stroke. Its co-primary endpoint included a composite of any of these events plus hospitalization for heart failure.
Overall, the composite primary endpoint occurred in 691 participants and 1,470 experienced the composite co-primary endpoint. When analyzed on a year-round basis there was no significant difference in the rates of these events between those who had received a flu vaccine and those who had not.

Prostate cancers remain localised in the majority of cases, giving affected individuals a good chance of survival. However, about 20% of patients develop incurable metastatic prostate cancer, resulting in approximately 5,000 deaths each year in Austria alone. Medical research has not yet adequately explained why metastases occur in some people and not in others. A research team at MedUni Vienna has now discovered specific changes in a protein that drive the growth and spread of prostate cancer. The study was recently published in the journal Molecular Cancer.
In the study, the researchers broke new ground and investigated the role of the protein KMT2C in prostate cancer. KMT2C is a genetic component that essentially functions as a regulator of central cellular processes. If KMT2C loses this regulatory ability due to typical cancer-related mutations, this encourages the proliferation of the cancer gene MYC. This in turn causes cells to divide at an increased rate, driving both growth and spread of the cancer.
New insights into the transition to metastasis
“Our study provides new insights into the previously poorly understood transition from localised prostate cancer to terminal metastatic prostate cancer,” says study leader Lukas Kenner (Department of Pathology at MedUni Vienna, Comprehensive Cancer Center of MedUni Vienna and University Hospital Vienna, Department of Laboratory Animal Pathology at Vetmeduni Vienna and the K1 Center CBmed), underlining the significance of the research work. In addition, the knowledge gained about the effects of KMT2C mutations may also generate new momentum for the diagnosis and treatment of prostate cancer.
Diagnosing aggressive progression at an early stage
KMT2C mutation status can be measured via a blood test, allowing early diagnosis of potentially aggressive progression in prostate cancers. In addition, MYC inhibitors could be used to prevent increased cell division, and hence metastasis, and it is hoped that further scientific studies will substantiate this. MYC inhibitors are essentially new cancer treatment drugs that have already been tested in clinical trials and — if further studies confirm this — could also be used in metastatic prostate cancer in the next few years. “Since a high level of KMT2C mutation characterises many types of cancer, such as breast, lung, colorectal, bladder and even skin cancer, our study results have a great deal of potential in the research, diagnosis and treatment of malignant cancers in general,” says Lukas Kenner.
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Depression, dizziness, difficulty focusing the gaze and balance problems. Many professional athletes who have sustained head trauma in sports have lingering symptoms that affect everyday life. Little help has been available as the cause has been unknown. A clinical study from Lund University in Sweden can now show that the problems originate in an injury to the vestibular nerve.
Athletes in contact sports such as ice hockey, football and skiing have an increased risk of sustaining a head injury. If the impact is severe enough, the athlete can suffer a concussion. Even minor head injuries can have serious consequences. The problems have been brought to light within American football, where players who have suffered from repeated concussions have developed dementia, severe depression and cognitive impairment.
In many cases, the symptoms after a concussion are temporary, but an increasing number of athletes experience long-term problems that make it difficult to work, go to school or play sports. The symptoms are aggravated by activity or impressions and include headaches, depression, anxiety, nausea, difficulty focusing and problems with balance.
“It has been unclear what causes the symptoms, and it is difficult for healthcare professionals to help these athletes. We wanted to investigate this further to find out what really causes the symptoms,” says Niklas Marklund, professor of neurosurgery at Lund University, consultant at Skåne University Hospital with a scientific interest in sports-related head injuries and one of the researchers behind the article.
A total of 42 people were included in the study. One group included 21 healthy athletes without previous trauma to the head, and the other 21 athletes who all suffered from sports-related concussions and who had experienced persisting symptoms for more than six months. All the participants underwent various tests in which the researchers examined, among other things, their balance organs. Using a so-called 7-Tesla MRI, the athletes’ brains were studied to understand more about what caused the symptoms. The researchers found impaired function of the balance organs in the inner ear of 13 athletes in the group with long-term problems. In the group of healthy athletes 3 people had similar findings.
“The test results show that the injury is located to the vestibular nerve, which is connected to the semicircular canals in a cavity inside the skull, and which is directly adjacent to the cochlea in the ear. These injuries lead to the inward nerve impulses not working properly, and the brain therefore does not receive important information about body movements and sensory impressions required to maintain a good balance,” says Anna Gard, doctoral student at Lund University, resident in neurosurgery at Skåne University Hospital and first author of the study.
When you suffer from a concussion, it is often because the head rotates too fast, for example when tackling in ice hockey.
“We have not examined athletes with short-term problems after blows to the head, so we cannot say anything about them. This study applies to athletes with prolonged symptoms after concussion. The rotation of the head that occurs in connection with a concussion could lead to a stretch of the vestibular nerve, which then leads to impaired function. Now that we have more knowledge about where the problems are located, it is easier to find possible therapies that could help these athletes,” concludes Niklas Marklund.
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A new study led by ISGlobal, an institution supported by “la Caixa” Foundation, identifies associations between DNA methylation patterns and gene expression levels in blood samples from children. The findings, published in eLife, provide researchers with a powerful tool to better understand the association between early environmental exposures, epigenetic changes and disease.
Cells from the same individual share the same genome but do not express the same genes. Each cell type expresses a different set of genes, which allows it to exert a unique function. This is regulated by the epigenome — chemical modifications of genome (including DNA methylation), which can turn genes on or off. Besides its central role in regulating development, the epigenome also allows cells to respond to environmental factors. Recently, many studies (called epigenome-wide association studies) have tried to link exposure to environmental factors with altered DNA methylation patterns and disease. However, most analyses do not allow to determine if and how these methylated sites affect the expression of nearby genes.
“Identifying associations between DNA methylation levels and gene expression might help us better interpret epigenome-wide association studies and understand the biological processes leading to disease,” says Mariona Bustamante, researcher at ISGlobal, who co-led the investigation together with Carlos Ruiz-Arenas from the Universitat Pompeu Fabra.
In this study, the research team aimed to identify associations between DNA methylation levels at particular positions of the genome with the expression of nearby genes, called expression quantitative trait methylation or eQTMs, using blood samples from 832 children, aged 6-11 years, of the Human Early Life Exposome (HELIX) project. Firstly, methylation and gene expression levels were assessed for each sample. Secondly, each gene was paired with the closest methylation site or sites. The analysis identified almost 40,000 significant associations between methylation levels and gene expression. In most cases, the methylation site was quite close to the regulated gene, and in 59% of cases, there was an inverse relationship between methylation and gene expression levels (meaning higher levels of methylation — lower gene expression). Only 13.8% of the associations identified were also found in adults. “This was expected, as it is known that DNA methylation and gene expression change with age, however differences in study designs can also explain this,” explains Carlos Ruiz-Arenas, first author of the study.
“Our results provide a catalogue of methylation-gene expression associations that could become a powerful tool to help researchers interpret epigenome-wide association studies in children,” notes Bustamante. The catalogue is publicly available at https://helixomics.isglobal.org/
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Patients kept at a body temperature of 37 C during major surgery had no fewer cardiac complications than patients kept at 35.5 C, according to data presented at the American College of Cardiology’s 71st Annual Scientific Session. There were also no differences in the number of infections or required blood transfusions in patients kept at cooler body temperatures.
Body temperature generally decreases during surgery, largely because anesthetic medications interfere with the body’s processes for regulating temperature. While practices vary around the world, nursing staff in Western countries typically use forced-air heaters to keep patients warm during surgery, with a target temperature of 36 C, or 96.8 F. This trial, one of the largest to date, sought to determine whether warming patients even more — to 37 C, or 98.6 F — would reduce the risk of cardiac complications, which are a leading cause of death in the first 30 days after major surgery.
Results showed no significant differences between groups for the trial’s primary endpoint, a composite of troponin elevation due to ischemia (an indicator of heart injury), non-fatal cardiac arrest or death from any cause within 30 days after surgery. Researchers also reported no differences for any of the trial’s secondary endpoints.
“This trial tells us that there is no benefit to aggressively warming patients to 37 C during surgery. It is simply unnecessary, and it doesn’t improve any substantive outcomes,” said Daniel I. Sessler, MD, Michael Cudahy professor and chair of the Department of Outcomes Research at Cleveland Clinic and the trial’s lead author. “Also, the results show that 36 C should not be considered the threshold for defining mild hypothermia since there was no harm at 35.5 C.”
The researchers enrolled 5,050 patients who had surgery at 13 medical centers, mostly in China. Participants had various major noncardiac surgical procedures, with a minimum duration of two hours and an average duration of four hours. Half of the patients were randomly assigned to receive routine care, with a target body temperature of 35.5 C, while half received aggressive warming, with a target body temperature of 37 C.
For patients assigned to routine care, nursing staff put a warming cover in position but did not activate it until the patient’s body temperature decreased to less than 35.5 C, resulting in an average group body temperature of 35.6 C. With the more aggressive warming protocol, nurses covered patients with a heated blanket for 30 minutes before surgery and then used two forced-air heaters to keep patients warmed to a mean of 37.1 C during surgery.
In addition to seeing no benefit in terms of the composite primary endpoint, the trial reported no significant differences between groups in terms of serious wound infections, length of hospitalization, hospital re-admissions or the need for blood transfusions. The investigators were surprised that rates of wound infections and transfusions were similar to previous studies, which suggested that both were more common in patients maintained at lower body temperatures.
Nearly all patients were enrolled in China, Sessler said, but the results should be generalizable to patients and health care settings in other countries.
“This study shows that it is reasonable to keep patients warm, but we saw no evidence whatsoever that it makes a difference if they’re just above or just below 36 C,” Sessler said. “Surgical patients should still be warmed, but there’s no need to be super-aggressive about the warming.”
The study did not assess less serious or non-medical outcomes, such as patient comfort or shivering. Sessler said that patients maintained at a lower body temperature may shiver or feel cold after surgery, but both are temporary and unlikely to have a meaningful health impact.
This study was simultaneously published online in The Lancet at the time of presentation. The study was partially funded by 3M.
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Patients with tricuspid regurgitation, a common and debilitating form of valvular heart disease, who received a novel investigational device intended to repair the defective valve experienced significant improvements in blood flow through the heart and in quality of life at one year, according to research presented at the American College of Cardiology’s 71st Annual Scientific Session.
“At one year of follow-up, the repair procedure appears to be safe and significantly reduced the severity of patients’ tricuspid regurgitation and improved their ability to function in daily life, maintaining gains that we previously saw at 30 days of follow-up,” said Adam B. Greenbaum, MD, associate professor of medicine and co-director of the Structural Heart and Valve Center at Emory University School of Medicine.
Tricuspid regurgitation affects an estimated 1.6 million people in the U.S. and increases as each generation ages. The study offers further validation for transcatheter edge-to-edge repair, a minimally invasive approach to the treatment of patients with the disease, Greenbaum said.
The tricuspid valve, one of four valves in the heart, controls blood flow between the heart’s two right chambers, the right atrium and the right ventricle. When the right atrium fills with blood, the valve opens, allowing the blood to flow into the right ventricle. Then, the valve closes tightly so that no blood flows backward into the right atrium. Tricuspid regurgitation occurs when the valve doesn’t close tightly, allowing blood to flow backward and causing the heart to pump harder to push enough blood out into the body. Patients with tricuspid regurgitation often feel tired and experience shortness of breath. As the condition worsens over time, it may cause symptoms such as an enlarged liver, a swishing sound when the heart beats, a fluttering feeling in the chest and swelling in the abdomen, legs, ankles or feet.
Patients with tricuspid regurgitation are commonly treated with diuretics, drugs that are also used to treat high blood pressure. Surgery to repair or replace a poorly functioning tricuspid valve is often done at the same time a patient undergoes surgery for a problem on the left side of the heart. Minimally invasive options are needed to treat tricuspid regurgitation, Greenbaum said, as most patients with the condition are older and may have other health problems that make them poor candidates for open-heart surgery.
The CLASP-TR study is a feasibility study of an investigational transcatheter repair system for tricuspid regurgitation. A long, flexible tube called a catheter is threaded through a vein to insert a tiny device that resembles a clothespin into the tricuspid valve. The pin grasps the flaps that open and close the valve, reducing the amount of blood that flows backward. The study endpoints included a composite of major adverse events at 30 days (e.g., death due to cardiovascular disease, heart attack, stroke, kidney failure, severe bleeding); evidence on an echocardiogram of a reduction in backward blood flow; and death from any cause, distance walked in six minutes and scores on two measures of heart failure severity.
A preliminary report published in February 2021 found that at 30 days of follow-up, the repair system substantially reduced tricuspid regurgitation, produced few adverse events, and significantly improved patients’ ability to function, exercise capacity and quality of life. The current study reports results after one year of follow-up.
A total of 65 patients (average age 77, 55% women) received the investigational device, 70% of whom had tricuspid regurgitation that was rated “massive” or “torrential” (the two highest grades of severity on a five-point scale) despite treatment with diuretics. In addition, most had other health problems that made them poor candidates for surgery, including atrial fibrillation (a type of abnormal heart rhythm), liver or kidney disease and pulmonary hypertension (a type of high blood pressure that affects the right side of the heart and the arteries in the lungs).
The COVID-19 pandemic affected the researchers’ ability to obtain one-year follow-up data for all treated patients, Greenbaum said. For example, some patients completed follow-up questionnaires that could be done remotely but did not complete tests that had to be done at the hospital, such as the echocardiogram and six-minute walk test. In addition, several patients died (although none died because of the repair procedure). In a few patients, the procedure was unsuccessful because the device failed to attach to the flaps in the tricuspid valve; and a few patients were lost to follow-up.
Ultimately, one-year follow-up results were available for 49 patients. Seven patients (10.8%) died and 12 (18.5%) were rehospitalized for heart failure. These results compare with an expected one-year mortality rate of about 30% for patients with tricuspid regurgitation, Greenbaum said. Among 36 patients with available data at one year, all achieved a reduction of at least one grade in the severity of their tricuspid regurgitation; 75% saw a reduction of at least two grades; and 86% achieved an overall grade of moderate or less. Eleven patients (16.9%) experienced a major adverse event. Significant improvements were seen in heart failure severity, the six-minute walk test and patient-reported quality of life.
Longer follow-up is needed to determine how well the device continues to perform and how well patients do at two years or five years of follow-up, Greenbaum said. Limitations of the study include low patient treatment numbers and an absence of a comparison group. Greenbaum said a randomized trial is now underway that will compare outcomes for patients treated with the investigational device and patients who receive optimal medical therapy with diuretics.
The study was funded by Edwards Lifesciences Corporation, maker of the tricuspid valve repair system used in the study.

Researchers from Tel Aviv University proved that a drug delivery system based on lipid nanoparticles can utilize RNA to overcome resistance to both chemotherapy and immunotherapy in cancer treatments. The study opens a new path to a personalized and precisely targeted battle against cancer. The results were published in the scientific journal Advanced Materials.
The study was led by TAU Vice President for R&D Prof. Dan Peer, Head of the Laboratory of Precision Nanomedicine at the Shmunis School of Biomedicine and Cancer Research, Wise Faculty of Life Sciences, and a member of the Roman Abramovich Center for Nanoscience and Nanotechnology, together with post-doctoral researcher Dr. Seok-Beom Yong of South Korea. The study was funded via an ERC grant from the European Union and a research scholarship from the Korean government.
Chemo-immunotherapy, which combines chemotherapy with immunotherapy, is considered the most advanced standard of care for various types of cancer. While chemotherapy destroys cancer cells, immunotherapy encourages the cells of the immune system to identify and attack the remaining cancer cells. However, many patients fail to respond to chemo-immunotherapy, which means that the treatment is not sufficiently targeted. Prof. Peer and his team are the first in the world to prove the feasibility of a drug delivery system based on lipid nanoparticles that release their load only at the specifically targeted cells — cancer cells for chemotherapy and immune cells for immunotherapy.
“In our system a single nanoparticle is capable of operating in two different arenas,” explains Prof. Peer. “It increases the sensitivity of cancer cells resistant to chemotherapy, while also reinvigorating immune cells and increasing their sensitivity to cancer cells. Thus, with one precisely targeted nanoparticle we provide two different treatments, at very different sites. We tested this system in two types of lab models — one for metastasized melanoma, and the other for a local solid tumor. In both populations we observed positive effects of our delivery system.”
The new development by Prof. Peer’s team builds from another recent discovery: an enzyme called HO1 is used by cancer cells for both resisting chemotherapy and concealing themselves from the immune system. Silencing HO1 in the tumor is thus considered an optimal strategy in clinical research, but so far, all attempts to silence the enzyme led to severe side effects.
“Chemo-resistant tumors pose a significant challenge in our endless battle against cancer,” says Prof. Peer. “We aim to silence the enzyme HO1 which enables tumors to develop resistance to chemotherapy, and to conceal themselves from the immune system. But existing methods for silencing HO1 resemble using an F-16 fighter jet to blast a tiny ant. Our new nanodrug knows how to precisely target the cancer cells, silence the enzyme, and expose the tumor to chemotherapy, without causing any damage to surrounding healthy cells. Afterwards, the same nanoparticle goes on to the T-cells of the immune system and reprograms them to identify cancer cells. Active, highly aggressive tumors are able to conceal themselves from the immune system, and we restore the immune cells’ ability to recognize the cancer as a foreign body and attack it.”
“This is the first instance of a single drug based on an RNA-loaded nanoparticle doing two very different, even opposite jobs,” adds Prof. Peer. “This is only an initial study, but it has enormous potential in the ongoing fight against cancer.”
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