Study investigates 12-month respiratory outcomes in patients hospitalized for COVID-19

A new study has shown that most patients discharged from hospital after experiencing severe COVID-19 infection appear to return to full health, although up to a third do still have evidence of effects upon the lungs one year on.

COVID-19 has infected millions of people worldwide. People are most commonly hospitalized for COVID-19 infection when it affects the lungs – termed COVID-19 pneumonia. Whilst significant progress has been made in understanding and treating acute COVID-19 pneumonia, very little is understood about how long it takes for patients to fully recover and whether changes within the lungs persist.

In this new study, published in The Lancet Respiratory Medicine, researchers from the University of Southampton worked with collaborators in Wuhan, China, to investigate the natural history of recovery from severe COVID-19 pneumonia up to one year after hospitalization.

83 patients were recruited after they were discharged from hospital following severe COVID-19 pneumonia and were followed up after three, six, nine and twelve months. At each time point they underwent clinical assessment as well as measures of how well the lungs function, a CT scan of their chest to take a picture of the lungs, and a walking test.

Over 12 months in most patients there was an improvement in symptoms, exercise capacity, and COVID-19 related CT changes. By 12 months the majority of patients appeared to have fully recovered although about 5% of patients still reported breathlessness. A third of patients' measures of lung function were still reduced – in particular how efficiently oxygen is transferred in the lungs into the blood – and this was more frequently found in women than in men. In around a quarter of patients CT scans showed there were still small areas of change in the lungs, and this was more common in patients with more severe lung changes at time of hospitalization.

Dr Mark Jones, Associate Professor in Respiratory Medicine at the University of Southampton and NIHR Southampton Biomedical Research Centre who co-led the study said, "the majority of patients with severe COVID-19 pneumonia appeared to fully recover, although for some patients this took many months. Women were more likely to have persistent reductions in lung function tests and further investigation is needed to understand if there is a sex specific difference in how patient's recover. We also don't yet know what happens beyond 12 months and this will need ongoing study."

The researchers acknowledged that this study only involved a small number of patients and the findings will require confirmation in additional studies, however they have identified a number of important implications.

Firstly, our research provides evidence that routine respiratory follow-up of patients hospitalized with COVID-19-pneumonia is required. Secondly, given the length of time it takes for some patients to recover it suggests that research into whether exercise programmes help patients recover more quickly is required. Finally, it highlights the need for treatment strategies to prevent the development of long term COVID-19 related lung changes."

Dr Yihua Wang, Study Co-Lead, Lecturer in Biomedical Sciences, University of Southampton and NIHR Southampton Biomedical Research Centre

Source:

University of Southampton

Journal reference:

Wu, X., et al. (2021) 3-month, 6-month, 9-month, and 12-month respiratory outcomes in patients following COVID-19-related hospitalisation: a prospective study. The Lancet Respiratory Medicine. doi.org/10.1016/S2213-2600(21)00174-0.

Posted in: Medical Research News | Disease/Infection News | Healthcare News

Tags: Blood, CT, Exercise, Hospital, Lungs, Medicine, Oxygen, Pneumonia, Research, Respiratory, Walking

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Novel PET tracer is safe and can clearly identify early stages of rheumatoid arthritis

New research shows that a novel positron emission tomography (PET) tracer that targets inflammation is safe and can clearly identify early stages of rheumatoid arthritis. The promising PET tracer, 68Ga-DOTA-Siglec-9, rapidly clears from blood circulation, has a low radiation dose, and can be easily produced. This first-in-human study was published in the April issue of the Journal of Nuclear Medicine.

Inflammation is a significant part of several chronic diseases, including rheumatoid arthritis and its related issues. While PET imaging with 18F-FDG is a valuable tool for the diagnosis and monitoring of the effects of treatments, it is not specific enough to assess inflammation.

It's important to detect inflammation early so that patients can receive the best treatment. Our institution has worked for several years to develop an imaging agent that targets areas of inflammation, and in this study, tested its effectiveness in humans for the first time."

Anne Roivainen, PhD, Professor of Preclinical Imaging and Drug Research, Turku PET Centre, University of Turku and Turku University Hospital in Finland

To evaluate the radiotracer's safety and biodistribution characteristics, six healthy study participants underwent whole body 68Ga-DOTA-Siglec-9 PET/computed tomography scans. 68Ga-DOTA-Siglec-9 was well-tolerated and cleared quickly from the blood, and its radiation dose was similar to other 68Ga tracers. In one additional study participant with rheumatoid arthritis, the tracer was able to clearly detect joints with arthritis.

"We have proven that the characteristics of 68Ga-DOTA-Siglec-9 are favorable for use in patient imaging studies," remarked Roivainen. "Future studies will clarify whether 68Ga-DOTA-Siglec-9 PET imaging has the potential to detect other inflammatory diseases early. It could also help to evaluate the effectiveness of treatments and promptly identify patients who are unlikely respond to therapy."

Source:

Society of Nuclear Medicine and Molecular Imaging

Journal reference:

Viitanen, R., et al. (2021) First-in-Humans Study of 68Ga-DOTA-Siglec-9, a PET Ligand Targeting Vascular Adhesion Protein 1. Journal of Nuclear Medicine. doi.org/10.2967/jnumed.120.250696.

Posted in: Medical Science News | Medical Research News | Medical Condition News

Tags: Arthritis, Blood, Chronic, Computed Tomography, CT, Heart, Hospital, Imaging, Immunology, Inflammation, Laboratory, Ligand, Medicine, Molecular Imaging, Nuclear Medicine, Oncology, Positron Emission Tomography, Preclinical, Preclinical Imaging, Protein, Radiology, Radiotherapy, Research, Rheumatoid Arthritis, Rheumatology, Theranostics, Tomography, Vascular

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Surgery to correct congenital heart disease linked to increased risk of adult hypertension

In a medical records study covering thousands of children, a U.S.-Canadian team led by researchers at Johns Hopkins Medicine concludes that while surgery to correct congenital heart disease (CHD) within 10 years after birth may restore young hearts to healthy function, it also may be associated with an increased risk of hypertension — high blood pressure — within a few months or years after surgery.

Reporting their findings in the April 8, 2021, issue of JAMA Network Open, the researchers showed that children who had cardiac repair surgeries were 13 times more likely to develop hypertension as adults when compared with the general population.

"Congenital heart disease is among the most common forms of birth defects, and successful surgical interventions are usually performed before the age of 2; however, the specific risks of long-term, negative outcomes — including hypertension — are basically unknown for this population," says Chirag Parikh, M.D., Ph.D., director of the Division of Nephrology at the Johns Hopkins University School of Medicine and lead author of the new paper.

"So, we conducted what is believed to be the largest study with the longest follow-up ever of these children to better understand these risks and guide the development of methods to help them lessen the chance of hypertension-related cardiac disease or death," he says.

The hypertension study used the same data registry from a 2019 investigation of CHD repair and long-term risk of end-stage kidney disease.

Parikh says that clinical outcome studies in recent years provide evidence that surgical repair of heart problems during the first decade of life leaves behind some pathological changes that can continue in the cardiovascular system.

In an attempt to more precisely measure the problem of hypertension after childhood heart surgery, Parikh and his colleagues looked at medical records from seven linked Canadian patient databases. Since Canadians have universal access to health care services, the study population was less likely to have disparities and differences in the treatment and follow-up care they received.

From the list of all babies born in Ontario, Canada, between April 1, 2012, and March 31, 2015, the researchers selected 3,600 children who had surgeries to repair CHD within 10 years of birth, and matched them with 36,000 others who did not have the congenital condition nor any procedures performed on their hearts. The majority of the patients who had repair surgery were prematurely born males with low birth weights and around 150 days old at the time of their first surgery.

Cardiac repair surgeries performed on the patients were ranked from 1 to 4 in increasing complexity, with 43% being listed at categories 3 or 4 (the most complex), and including some even more complex than category 4. The two most commonly seen procedures (64%) were closure of a hole between the atria (upper chambers of the heart) or between the ventricles (lower chambers of the heart).

Both the cardiac repair surgery and the nonsurgery subjects were followed medically for up to 13 years, with data collected until death, diagnosis of hypertension or the end of the study (March 31, 2015). Of the 3,600 subjects who had surgery, 445 — or 12.4% — developed hypertension, compared with 398 out of 36,000 people — or 1.1% — who did not have the procedure. This means the children who had CHD repair surgery were 12 times more likely to become hypertensive.

The hypertension incidence rate — the total number of high blood pressure cases identified during the study period divided by the cumulative time in years for all of the patients participating (known as person-years) — also showed significantly higher risk of developing hypertension as an outcome of early age CHD repair surgery. For the surgery patients, the incident rate was 141.3 cases per 10,000 person-years compared with 11.1 cases per 10,000 person-years for those who did not have the surgery — a difference of nearly 13 to 1.

"We also saw that the more complex the cardiac surgery performed, the higher the risk for developing hypertension," Parikh says. "In the most extreme case, patients who had surgery to correct a hypoplastic left heart — a severe defect where the left side of the heart is underdeveloped — were three times more likely to develop hypertension than the congenital heart condition next in severity."

Other factors raising the risk of future hypertension were CHD repair surgery at age 3 months or younger, needing kidney dialysis during recovery from CHD repair surgery, and one or more cardiac surgeries after the initial repair.

Parikh cautions that medical records studies that "look back" at patient histories have limitations, but says that the research team's findings should be useful in guiding better long-term care for those at highest risk for hypertension, and subsequently, heart disease, stroke or kidney disease.

"For now, we recommend that children who have cardiac repair as infants be monitored more closely for hypertension throughout their lives," he says. "Future research will need to explore if early treatment of hypertension in these patients can prevent cardiovascular or renal problems later on."

Source:

Johns Hopkins Medicine

Journal reference:

Greenberg, J.H., et al. (2021) Long-term Risk of Hypertension After Surgical Repair of Congenital Heart Disease in Children. JAMA Network Open. doi.org/10.1001/jamanetworkopen.2021.5237.

Posted in: Child Health News | Medical Procedure News | Medical Research News | Medical Condition News

Tags: Biopharmaceutical, Birth Defects, Blood, Blood Pressure, Cardiac Surgery, Children, Congenital Heart Defect, Congenital Heart Disease, Dialysis, Health Care, Heart, Heart Defect, Heart Disease, Heart Surgery, High Blood Pressure, Hospital, Hypoplastic, Kidney, Kidney Disease, Medicine, Nephrology, pH, Research, Stroke, Surgery

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New biomarker of glucocorticoid action could help clinicians to tailor treatments

Researchers have uncovered pathways involved in the body's response to glucocorticoid treatments and identified a novel biomarker that could be used to monitor how these drugs work in patients, according to a clinical study published today in eLife.

A more reliable indicator of an individual's response to glucocorticoid drugs could be used to develop a clinically applicable test that could help tailor treatments and potentially minimize side-effects.

Glucocorticoids, such as cortisol, are a type of hormone with key roles in the body's response to stress. Glucocorticoid drugs are one of the most commonly prescribed treatments for a range of conditions, including for patients whose adrenal glands are unable to produce enough cortisol. The effects of glucocorticoids are complex, meaning the level of cortisol in the blood does not reliably reflect what is happening in the tissues. This makes it hard for medical professionals to know how to tailor treatments.

Side effects of glucocorticoid treatments are common in patients, indicating that current methods to monitor their action, which typically focus on clinical response or disease activity, are inadequate. We wanted to find some kind of biomarker that could be measured to monitor the action of glucocorticoids in individuals, with the hopes this will help clinicians understand how best to treat patients."

Dimitrios Chantzichristos, First Author, Head Physician, Section for Endocrinology-Diabetes-Metabolism, Sahlgrenska University Hospital, Sweden

The team studied patients with Addison's disease who lack the ability to produce their own cortisol. This allowed them to compare the activity in the tissues of the same patient both when their cortisol levels were low and when they were being restored by glucocorticoid treatments, helping account for variations between individuals.

Rather than focusing only on the metabolic products associated with glucocorticoid exposure, they also looked at gene expression and microRNAs in the patients using new computational approaches developed in collaboration with Dr Adam Stevens at the University of Manchester, UK. MicroRNAs are short strands of ribonucleic acid (RNA) that can regulate the expression of genes by interfering with protein production. The team analyzed these different factors in blood cells and body fat, an important metabolic tissue, as the patients' cortisol levels were changed, revealing close relationships between different elements involved in glucocorticoid action.

Among the elements they identified, a microRNA called miR-122-5p closely correlated with genes and metabolites that are regulated by the glucocorticoid treatments. To test this correlation, the team looked at miR-122-5p levels in blood from patients exposed to different levels of glucocorticoids from three independent studies and found the same pattern, supporting the idea that this microRNA could be a useful biomarker of glucocorticoid action.

"This potential biomarker can now be investigated in larger groups of patients with the aim to develop a clinically applicable test," concludes senior author Gudmundur Johannsson, Professor at the Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Sweden. "Our work has also increased our understanding of the action of glucocorticoids, which may help uncover their role in many common diseases such as diabetes, obesity and cardiovascular diseases."

This study was a collaborative effort between researchers at the Universities of Manchester (UK), Edinburgh (UK), Copenhagen (Denmark) and Gothenburg (Sweden), as well as Newcastle University (UK) and Sahlgrenska University Hospital (Sweden).

Source:

eLife

Journal reference:

Chantzichristos, D., et al. (2021) Identification of human glucocorticoid response markers using integrated multi-omic analysis from a randomized crossover trial. eLife. doi.org/10.7554/eLife.62236.

Posted in: Molecular & Structural Biology | Biochemistry

Tags: Addison's Disease, Biomarker, Blood, Cortisol, Diabetes, Drugs, Endocrinology, Gene, Gene Expression, Genes, Glucocorticoid, Hormone, Hospital, Medical Research, Medicine, Metabolism, Metabolites, MicroRNA, Nutrition, Obesity, Protein, Research, Rheumatism, Ribonucleic Acid, RNA, Stress

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Women experienced high rates of mental health problems early in COVID-19 pandemic

A study at the University of Chicago Medicine found U.S. women experienced increased incidence of health-related socioeconomic risks (HRSRs), such as food insecurity and interpersonal violence, early in the COVID-19 pandemic. This was associated with "alarmingly high rates" of mental health problems, including depression and anxiety. The research was published April 5 in the Journal of Women's Health.

Other studies have found evidence for higher rates of anxiety and depression and related issues, such as alcohol overuse, connected to the pandemic — but this study is the first to link early pandemic-related changes in HRSRs to mental health effects in women.

Most national surveys tend to report aggregated findings rather than stratifying by gender. Those early studies gave us snapshots of the health and behaviors of the whole population, but gave us limited insight on women. Yet, women constitute the majority of the essential workforce, including healthcare workers, and we wanted to make sure that women's experiences were being documented."

Stacy Lindau, MD, Professor of Obstetrics and Gynecology and Medicine-Geriatrics, UChicago Medicine

The researchers conducted a survey of 3,200 U.S. women over the age of 18 between April 10 and 24, 2020. More than 40% of participants reported experiencing at least one HRSR during the prior year, which included issues such as food insecurity, housing instability, difficulties with their utilities, transportation challenges and interpersonal violence; 22% reported experiencing two or more HRSRs during the year before the pandemic.

But by the first spring of the pandemic, nearly half of all women — including 29% of those who did not experience pre-pandemic HRSRs — reported new (incident) or worsening HRSRs. The greatest challenge was an increase in food insecurity. Nearly 80% of those without pre-pandemic HRSRs who reported a new HRSR became food insecure. Almost a quarter experienced interpersonal violence.

"It's incredible and concerning that nearly half of women — including more than a quarter of those who had no health-related socioeconomic risks — had experienced incident or worsening conditions," said Lindau. "It's even more striking that more than a quarter of the women who had none of these risks in January or February 2020 now had at least one by April.

That points to the likelihood that a large portion of women were already near the edge of vulnerability. When the world shut down, transportation became more difficult, food access became harder, and very soon after the crisis began, many women found themselves struggling to meet basic needs."

Those who experienced socioeconomic risks prior to the pandemic also experienced the greatest increase in insecurity. Three-quarters of women with pre-pandemic HRSRs experienced new or worsening risks during the early pandemic; 38% experienced two or more, with more than half experiencing increased food insecurity.

Significantly, the survey also found that 29% of women reported symptoms of depression and anxiety — nearly twice the estimated pre-pandemic rates. One in six women screened positive for symptoms of post-traumatic stress, a rate similar to that seen after other significant disasters, such as the SARS and Ebola epidemics. Those who experienced at least one new or worsening HRSR were at significantly higher risk of experiencing anxiety and post-traumatic stress.

"Given very high rates of these problems, we're really concerned about the current capacity of our mental health system," said co-author Marie Tobin, MD, Professor of Psychiatry at UChicago Medicine. "Women are principally responsible for parenting, family caregiving and other essential work — they are key to managing and recovering from this pandemic, and now are afflicted by very significant socioeconomic risk levels that appear to be drivers of anxiety, depression and traumatic stress. We should be especially concerned that socioeconomically vulnerable women are at high risk for developing pandemic-related psychiatric morbidity."

These results, the investigators say, should help spur healthcare providers and policy makers to address the underlying and modifiable health-related socioeconomic risk factors in order to prevent these negative outcomes.

"We can't change a person's gender, but we can act to ensure that all people have the basic nutrition and shelter they need to survive," said Lindau. "We can intervene on transportation barriers, we can pass policies to delay or offset rent or utilities payments. These are modifiable factors that can be addressed by leveraging the humanitarian resources of our communities and implementing policies that ensure everyone can live independently with their basic needs met. Ensuring equitable access to the basics would be a powerful buffer against mental illness in general and could help mitigate costly and painful mental health crisis among women and everyone who depends on us in the context of this and other public health emergencies."

Source:

University of Chicago Medical Center

Journal reference:

Lindau, S. T., et al. (2021) Change in Health-Related Socioeconomic Risk Factors and Mental Health During the Early Phase of the COVID-19 Pandemic: A National Survey of U.S. Women. Journal of Women's Health. https://doi.org/10.1089/jwh.2020.8879.

Posted in: Medical Condition News | Women's Health News | Disease/Infection News

Tags: Alcohol, Anxiety, Cancer, Children, Depression, Geriatrics, Gynecology, Health Systems, Healthcare, Hospital, Medicine, Mental Health, Nutrition, Obstetrics, Pandemic, Parenting, Physiology, Psychiatry, Public Health, Research, SARS, Stress

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Brain imaging may predict treatment outcomes for adolescents with anxiety disorders

As with any complex machine, sometimes a simple crossed wire or short circuit can cause problems with how it functions. The same goes for our brains, and even when the short circuit is uncovered, sometimes experts don't have a quick fix.

A new study reveals that an evidence-based treatment may "fix" this human short circuit and, with the help of brain imaging, might predict treatment outcomes for adolescents with anxiety disorders. University of Cincinnati researchers say this could determine medication effectiveness more quickly to help patients.

Study results showed that brain imaging was able to predict — after just two weeks of treatment with almost 80% accuracy — how much a patient would improve.

We also see [through imaging] that the medication in this study increases the strength of the connection between a brain area that generates anxiety and an area that serves as a 'brain brake' for the fear center. In essence, the medication allows the brain to dampen the overactivity of fear areas, and we see this dampening very early in the course of treatment using imaging."

Jeffrey Strawn, MD, Study's Senior Author, Associate Professor and Anxiety Expert, Department of Psychiatry and Behavioral Neuroscience at UC

In this National Institutes of Health-sponsored study, published in the Journal of the American Academy of Child and Adolescent Psychiatry, researchers used brain imaging (MRI) to see how 41 adolescents, ages 12-17, with anxiety disorders responded to a medication called escitalopram, versus a placebo, over eight weeks. Escitalopram is a medication known as a selective serotonin reuptake inhibitor (SSRI) that is approved by the Food and Drug Administration for depression in adolescents and for both depression and anxiety in adults.

Strawn, who is also a physician at Cincinnati Children's Hospital Medical Center and UC Health, says SSRIs work by boosting the activity of serotonin in the brain. Serotonin is one of the chemical messengers that nerve cells use to communicate with one another and one that is involved in anxiety disorders. These medications block the recycling of serotonin into nerve cells, making more serotonin available to improve transmission of messages between neurons.

"These medications are an effective treatment for many adolescents with anxiety disorders. However, how much a specific patient will benefit is difficult to predict," he continues.

He says clinicians typically need six to eight weeks of the patient being on the medication in order to evaluate whether or not the treatment is going to work. "But with the brain imaging in this study, doctors could determine — after just two weeks — if they would need an alternative treatment. Knowing this early in treatment could greatly improve outcomes for patients," he adds. "This study helps clinicians understand how the medication — even early in treatment — changes brain circuits that are involved in anxiety and can help to get patients back to their normal lives more quickly."

Larger studies are needed to further test this, but the results are promising and, as Strawn notes, are really important for better treating adolescents with anxiety disorders.

"Anxiety disorders are the most common mental illnesses in the U.S., with approximately 4.4 million children and adolescents affected," he says. "These disorders are not only common in children and teens, but, if untreated, result in considerable personal and economic cost over the lifetime.

"This study uncovers a way to predict how effectively a medication will treat anxiety in kids and reveals that brain changes occur within two weeks of starting the medication. Additionally, the changes that occur in the brain can predict treatment response and improvement over time which is incredibly beneficial for physicians and can help us determine promising biomarkers for drug development. While not necessarily a quick fix, this could be a quicker fix that could help patients tremendously and improve their quality of life."

Source:

University of Cincinnati

Journal reference:

Lu, L., et al. (2021) Acute Neurofunctional Effects of Escitalopram in Pediatric Anxiety: A Double-Blind, Placebo-Controlled Trial, California. Journal of the American Academy of Child and Adolescent Psychiatry. doi.org/10.1016/j.jaac.2020.11.023.

Posted in: Child Health News | Medical Science News | Medical Research News

Tags: Adolescents, Anxiety, Brain, Children, Depression, Hospital, Imaging, Mental Health, Nerve, Neurons, Neuroscience, Placebo, Psychiatry, Serotonin

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VHIO-born spin-off receives approval to initiate Phase I/II clinical trial of novel Myc inhibitor

Co-founded back in 2014 by VHIO's Laura Soucek, CEO of the enterprise, and Marie-Eve Beaulieu, Chief Scientific Officer (CSO) of the company, VHIO-born spin-off Peptomyc S.L. has just announced that it has received approval from the Spanish Agency of Medicines and Medical Devices for conducting clinical trials in Spain (AEMPS), to initiate the first-in-human Phase I/II clinical trial with its first compound – a disruptive Myc inhibitor, Omomyc (OMO-103).

Building on the proven preclinical efficacy and safety of the Omomyc cell-penetrating peptide (CCP) in mouse models, and Peptomyc's company's successful development of anti-Myc peptides for the treatment of several tumor types, this latest milestone represents a greatly anticipated 'leap' into the clinical research setting and an important step forward in becoming the first ever clinically viable and direct inhibitor of Myc – a protein implicated in the formation of most tumor types.

Commenting for VHIO's Global Communications, Laura Soucek, Principal Investigator of VHIO's Mouse Models of Cancer Therapies and an ICREA Research Professor said, "MYC has been considered an 'undruggable' cancer target for many years. We have previously shown that Myc blockade has an excellent therapeutic effect in several mouse models, with mild side effects that are well tolerated and reversible. Now that we have received approval to initiate our early phase clinical trial, we can further progress in testing the safety and efficacy of our Omomyc-based therapy for the benefit of those who matter the most – our patients."

Over the last 20 years Laura's determined research efforts have centered on proving countless cynics wrong in her ambitions to combat resistance to therapy and combat cancer cell spread through clinically inhibiting the Myc oncogene. Found deregulated in most, if not all tumor types, and as a key driver of cancer progression and maintenance, Myc is consequently a major contender as a cancer target and yet, promise of its inhibition has not yet been successfully translated into benefits at the patient level.

While several factors including Myc's nuclear localization, lack of identified ligand binding site, and its function in maintaining normal tissues, are responsible for both this frustrating scenario as well as the sustained belief that it is in fact an impossible cancer target, Laura and her team are now silencing the sceptics by finally pushing Myc inhibition into the clinic.

At the preclinical level, we have reported the efficacy of Omomyc as a cell penetrating peptide – essentially, a mini-protein with the ability to enter cells and reach its target compartment, namely, the nucleus. The successful intravenous systemic administration of our mini-protein MYC inhibitor against lung cancer and other malignancies, has led to this week's exciting development."

Marie-Eve Beaulieu, Peptomyc's Chief Scientific Officer

She added, "Our strategy differs immensely from other previous approaches aimed at inhibiting Myc. Our Omomyc mini-protein is large enough to accurately fold and adapt to Myc's disordered structure, which determines the specificity of inhibition. At the same time, it is small enough to penetrate tumor cells and nuclei in order to reach its target. By conducting our first-in-human early phase clinical trial, we hope to drive this novel therapy into the clinic for the more effective treatment of multiple tumor types".

Twenty patients with advanced solid tumors across various cancer types, whose disease has progressed after previous treatments, will be enrolled in the Phase I study. This clinical trial will be carried out at three different Spanish sites: our Vall d'Hebron University Hospital (HUVH), also located within the Vall d'Hebron Barcelona Hospital Campus, the HM Sanchinarro University Hospital, and the Fundación Jiménez Díaz University Hospital (Madrid).

VHIO's Elena Garralda, Director of our Research Unit for Molecular Therapy of Cancer (UITM) – "la Caixa" Foundation, and Head of Early Clinical Drug Development at our Institute, is the Principal Investigator of Peptomyc's clinical study at Vall d'Hebron. She noted, "I am honored and privileged to participate in this study of a VHIO-developed molecule. Since Myc has traditionally been considered as an impossible drug target, this clinical trial represents a pivotal development. Confirmation of OMO-103's safety and efficacy in patients would be extremely important for the future treatment of cancer".

"To get to where we are today has been a long and challenging journey. While we have had to overcome many obstacles, we have successfully proven our hypothesis about Myc by achieving amazing results in animal models. We very much hope that Omomyc will meet the same expectations in clinical research so that we can ultimately provide new hope for cancer patients, particularly for those suffering from advanced disease," concluded Laura Soucek.

The preclinical development of Omomyc was possible thanks to the support received from Worldwide Cancer Research (WCR/AICR), European Research Council (ERC) – one Consolidator and two Proof of Concept grants – Instituto de Salud Carlos III (Institute of Health Carlos III), Fondo de Investigación en Salud (FIS) grants, Fero Foundation, and the BBVA Foundation, among other funding entities.

Source:

Vall d'Hebron Institute of Oncology

Posted in: Drug Trial News | Medical Condition News

Tags: Cancer, Cell, Clinical Trial, Compound, Efficacy, Hospital, Ligand, Lung Cancer, Molecule, Oncogene, Peptides, Preclinical, Protein, Research, Tumor

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Jordan health minister sacked after oxygen outage kills seven COVID-19 patients

AMMAN (Reuters) – Jordan’s health minister was dismissed on Saturday after seven people died following an oxygen outage in a hospital treating coronavirus patients, and police were deployed to hold back hundreds of angry relatives, state media and witnesses said.

The oxygen failure on Saturday hit intensive care, maternity and coronavirus wards in the new Salt government hospital west of the capital Amman.

Prime Minister Bisher al Khaswaneh said he had fired Health Minister Nathir Obeidat. In a public apology, he said his government bore full responsibility for the incident.

“This is a gross mistake that cannot be justified or accepted. I feel ashamed of it and won’t justify it,” Khaswaneh said, adding that he was awaiting the results of a judicial investigation.

Obeidat said he bore “moral responsibility” for the deaths of the patients, who were being treated for COVID-19 when wards ran out of oxygen for nearly an hour.

King Abdullah visited the hospital in a move officials said was intended to defuse tensions. Anger with the authorities has in the past triggered civil unrest in Jordan.

“How can a hospital like this see something like this happening?” he said on entering the multi-million-dollar hospital, which went into operation only last August.

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Some politicians said the incident pointed to major mismanagement in government hospitals.

Jordan is facing a spike in COVID-19 infections attributed mainly to the fast transmission of the coronavirus variant first identified in Britain, and announced stricter measures to curb the spread of COVID-19 last week.

Jordan reported 8,300 new cases of COVID-19 on Thursday, the highest daily death toll since the pandemic first surfaced in the kingdom a year ago.

Jordan, with a population of around 10 million, has recorded 385,533 cases of COVID-19 and 5,224 deaths.

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Immune cells in cerebrospinal fluid could be novel biomarkers to immune-based therapies

Results from a study led by Joan Seoane, Director of Preclinical and Translational Research co-program at VHIO and ICREA Professor, show that immune cells accessing cerebrospinal fluid faithfully recapitulate the characteristics of cells identified in brain metastasis, and could therefore constitute novel biomarkers of response to immune-based therapies.

Immune checkpoint inhibitors including anti-PD1, anti-PD-L1, and anti-CTLA4, have shown significant clinical benefits in patients with progressive or metastatic solid tumors, including some brain metastasis.

Notably, these immune-based therapies have improved outcomes for some of those suffering from lung cancer and melanoma. Together, these tumor types (represent between 30-40% of all cancers), along with breast cancer, are three common malignancies that lead to brain metastases.

"One of the major challenges in improving outcomes for patients suffering from brain metastases caused by these cancers is that new lesions can differ immensely from the primary tumor, and thus respond in a different way to immune-based therapies," observes Joan Seoane, co-Corresponding Author of this present study that published today in Nature Communications.

Brain metastases are the most frequent tumor of the brain, with a dismal prognosis. While a fraction of patients benefits from treatment with immune checkpoint inhibitors, the majority do not. Predicting response to these therapies necessitates the characterization of tumor specimens.

Due to the anatomical location of brain tumors and the risk of surgical procedures, accessing samples from brain malignancies is challenging.

Results from previous studies led by Joan Seoane, as well as those of other groups, have evidenced that cerebrospinal fluid can provide vital insights into the genomic characteristics of brain tumors and therefore be used as a minimally invasive liquid biopsy.

Spurred by these findings, the investigators conducted this present research to establish whether they could effectively characterize the immunological phenotype through the analysis of cerebrospinal fluid.

To test this hypothesis, Joan Seoane's team analyzed samples from 48 patients with brain metastasis. These samples were obtained thanks to the generosity of patients receiving treatment at our Vall d'Hebron University Hospital (HUVH), as well as the Hospital Clínic in Barcelona, who gave their full consent to use their samples.

The collection of samples was possible thanks to the dedication and expertise of these hospitals' Neurosurgery Services.

The researchers assessed the immune cells present in the brain metastases, and in parallel, performed immune cell profiling of the cerebrospinal fluid. They sought to identify which cell types were present in the cerebrospinal fluid and compare them with those obtained from the metastatic lesions.

"By establishing similarities between the two, we have identified a novel and minimally invasive method that can allow us to predict response to immunotherapy in these patients. This pioneering approach could more precisely guide clinical decision making in treating these patients with immune-based therapeutic strategies," adds Joan Seoane.

By analyzing the cerebrospinal fluid, Joan Seoane's team has been able to identify the T-cells that recognize the tumor, and those that are active in treatment.

Each immune T-cell has a unique sequence that recognizes a particular tumor antigen. When their tracing and targeting commence, these cells are activated and begin to proliferate. Through this study, we have been able to characterize the individual sequences of immune cells and, in this way, identify which immune cells are fighting the tumor and discern how they evolve over time."

Joan Seoane, Study Co-Corresponding Author and Director of Preclinical and Translational Research Co-Program, ICREA Professor, Vall d'Hebron Institute of Oncology

The study was also carried out in collaboration with colleagues at the National Centre for Genomic Analysis-Centre for Genomic Regulation (CNAG-CRG), Barcelona. Directed by Holger Heyn, Head of CNAG-CRG's Single Cell Genomics Team, theu performed single-cell transcriptome sequencing of around 6000 cells by scRNA-seq technology.

"Single-cell transcriptome sequencing provides the highest resolution for the detection and monitoring of several different diseases. The identification of clonal T-cells in both metastasis and liquid biopsy is of particular interest. We have shown that the sequencing of T-cell receptors provides a cellular barcode that can be assessed outside of the tumor. Importantly, this approach opens up new avenues for the detection of systemic disease," concludes Holger Heyn, co-Corresponding Author of this present study.

Source:

Vall d'Hebron Institute of Oncology

Journal reference:

Rubio-Perez, C., et al. (2021) Immune cell profiling of the cerebrospinal fluid enables the characterization of the brain metastasis microenvironment. Nature Communications. doi.org/10.1038/s41467-021-21789-x.

Posted in: Cell Biology | Genomics

Tags: Antigen, Biopsy, Brain, Brain Metastases, Breast Cancer, Cancer, Cell, DNA, Genomic, Genomics, Hospital, Immunology, Immunotherapy, Lung Cancer, Medulloblastoma, Melanoma, Metastasis, Neurosurgery, Oncology, PD-L1, Phenotype, Preclinical, Research, T-Cell, Tumor

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A region within GLI1 gene could potentially be targeted as cancer treatment

Scientists from the Stanley Manne Children's Research Institute at Ann & Robert H. Lurie Children's Hospital of Chicago found that a region within the DNA of the cancer-promoting GLI1 gene is directly responsible for regulating this gene's expression. These findings, published in the journal Stem Cells, imply that this region within GLI1 could potentially be targeted as cancer treatment, since turning off GLI1 would interrupt excessive cell division characteristic of cancer.

From previous research, we know that GLI1 drives the unrelenting cell proliferation that is responsible for many cancers, and that this gene also stimulates its own expression. We established in living human embryonic stem cells that removing the GLI1 regulatory region eliminated GLI1 expression and halted its activity. These findings are promising and could point to a therapeutic target for cancer."

Philip Iannaccone, MD, PhD, Co-Senior Author, Professor Emeritus at the Manne Research Institute, Lurie Children's and Northwestern University Feinberg School of Medicine

Dr. Iannaccone and colleagues used CRISPR gene editing technology to delete the binding region of the GLI1 DNA in human embryonic stem cells. They found that without this region, GLI1 remained turned off, which interfered with the gene's normal activity of driving embryonic development of blood, bone, and nerve cells.

"A surprising aspect of this work was that turning GLI1 off affected stem cell differentiation to all three embryonic lineages," says first author Yekaterina Galat, BS, Research Associate at the Manne Research Institute at Lurie Children's.

"The developmental function of GLI1 ends after birth, so if we manage to stop its expression in the context of cancer, it should not have negative consequences to normal biology," explains Dr. Iannaccone.

GLI1 expression is associated with about a third of all human cancers. In addition to promoting cell proliferation, GLI1 expression increases tumor cell migration and is associated with resistance to chemotherapy drugs.

"Our team plans to study GLI1 associated proteins that assist in regulation of GLI1 expression through its binding region," says Dr. Iannaccone. "Targeting these proteins as a means to stop GLI1 activity could prove to be a fruitful treatment strategy for cancer."

Source:

Ann & Robert H. Lurie Children's Hospital of Chicago

Posted in: Medical Science News | Medical Research News | Medical Condition News

Tags: Blood, Bone, Cancer, Cancer Treatment, Cell, Cell Division, Cell Migration, Cell Proliferation, Chemotherapy, Child Health, Children, CRISPR, DNA, Drugs, Embryonic Development, Embryonic Stem Cells, Gene, Hospital, Medicine, Nerve, Proliferation, Research, Stem Cells, Tumor

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