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WASHINGTON - (June 4, 2020) - A distinguished panel of medical experts, state and federal health officials, and congenital heart disease parent advocates published recommended updates to the current American Academy of Pediatrics' protocol for detecting critical congenital heart disease (CCHD) in newborn babies using pulse oximetry. The recommendations were released online by the journal Pediatrics. Updates include:

Key algorithm changes to simplify the passing threshold and trigger clinical assessment faster when a child's oxygen saturation is low

A call for an investment in public health infrastructure to allow for improved data collection of population level screening outcomes across states

Increased education about the tool's strengths and limitations

"In less than ten years, this non-invasive, low-cost screening tool and algorithm that started as a regional pilot program has become a critical part of the Recommended Uniform Screening Panel (RUSP) for every newborn in the United States," says Gerard Martin, M.D., cardiologist at Children's National Hospital and a lead author of the study recommendations. "We estimate that at least 120 babies' lives are saved by this tool in the U.S. every year, and we think the tool can save even more as it grows to become a standard of newborn care around the world."

Key algorithm changes

Screening failed if oxygen saturation in hand OR foot is less than 95%. The panel found evidence to recommend a screening fail or retest if either the right hand or lower extremity shows an oxygen saturation of less than 95%. The current American Academy of Pediatrics (AAP) algorithm recommends both hand and foot saturations must be less than 95% or a difference of 3% between the two to trigger a retest or a screening fail.

Eliminate second retest. Clinical assessment is now recommended after a newborn's oxygen saturation does not meet passing criteria in the initial test and one retest. The current AAP algorithm calls for up to two retests to minimize false positives. However, the evidence showed that eliminating the second retest requirement ensures children who may need urgent attention are able to get assessed and treated sooner with fewer retests.

Continue screening between 24 to 48 hours after birth. The panel decided the current recommended screening window between 24 and 48 hours after birth would remain the same given the increase in false positives when screening is completed too early. However, the recommendation acknowledges that completing screening before 24 hours has passed is acceptable in cases where early discharge of mother and baby is under consideration.

The panel considered several additional updates to the U.S. algorithm, but did not feel the evidence was strong enough to warrant further changes at this time.

Uniform public health CCHD reporting and clinician training

Though screening is required in all 50 states, the panel found that data collection is inconsistent across states. This makes it difficult to assess trends in effectiveness and identify any screening gaps on a national scale.

"Every state has done a good job of making sure that newborns are screened in the appropriate window," says Matt Oster, M.D., MPH, director of the Cardiac Outcomes Research Program at Children's Healthcare of Atlanta, and another study author. "However, variations in reporting, including in the definition of critical congenital heart disease make it difficult to know precisely how effective the tool is. It's critical that we help public health programs focus on protocol adherence and standardize data collection so we can accurately gauge the cases we capture and those we miss."

Training for providers; education for parents

The panel also emphasized the importance of making sure every care provider is trained to administer and record results in a uniform way.

As part of the RUSP in the United States, every baby born is required to receive the pulse oximetry screening within the first 24 to 48 hours, along with a battery of other screening tools.

"We need to do a better job of explaining to parents that a failed pulse oximetry screen simply triggers a closer clinical assessment," Dr. Martin says. "It doesn't indicate a specific issue other than a low level of oxygen saturation in the infant's body. Further clinical evaluation will tell us more and help us find any diagnosis."

The future of pulse oximetry to detect CCHD

Pulse oximetry screening continues to grow in the United States and other countries. The panel recommended a continuing effort by organizations such as the AAP, the American College of Cardiology and the American Heart Association to lead implementation of this inexpensive screening tool around the world. In 2014, the World Health Organization estimated that doing so might save more than 750,000 lives by the year 2030.

Philadelphia, June 4, 2020 - Head injuries that lead to concussions can happen at any age, and children impacted by concussions have different needs and recovery patterns. In a new study, researchers at Children's Hospital of Philadelphia (CHOP) have performed the most comprehensive characterization of elementary school-age concussions to date, revealing an opportunity to improve outcomes for this age group through more consistent visio-vestibular assessments at the initial health care visit. The findings were published today in the Journal of Pediatrics.

Many recent studies on pediatric concussions have focused on adolescent athletes, leading to changes in how clinicians diagnose and actively manage their concussions. But little is known about delivery of clinical care for young children with concussion who are different developmentally and in their goals for recovery than older youth.

"Since one-third of pediatric and adolescent concussion injuries occur in elementary school-age children, we set out to provide a comprehensive description of children ages 5-11 years who were diagnosed with concussion to pinpoint opportunities to improve the quality of diagnosis and care for this age group," said lead author Christina L. Master, MD, a sports medicine pediatrician at CHOP, a senior fellow at the Center for Injury Research and Prevention (CIRP), and Co-Director of the CHOP's Minds Matter Program.

The Minds Matter team collaborated with colleagues from with the U.S. Centers for Disease Control and Prevention (CDC), utilizing CHOP's single, linked electronic health records (EHR) system to analyse retrospective data on more than 1,500 patients ages 5-11 years and diagnosed with a concussion over a recent one-year period.

The study found that vision and balance issues were as common in this population as they are in adolescents. However, specific visio-vestibular assessments were not consistently performed at the time of diagnosis. In particular, these assessments occurred much less frequently outside of specialty care practices. Initial visits were evenly split between a primary care physician (49%) and an emergency department or urgent care (49%), with the remaining 2.1% seen in specialty care first, although it's important to note that 24.7% of all patients saw a specialist at some point in their care. Additionally, 21% of patients saw a school nurse, highlighting the important role nurses play in the identification and proper monitoring and management of these patients.

Approximately two-thirds of patients in this study (66.1%) self-reported visio-vestibular problems. Overall, 74.3% of patients had a visio-vestibular assessment at some point in their care and among these patients, 62.7% had identifiable deficits.

When it comes to providing concussion recovery planning to families, less than half (43.8%) of all concussed patients were provided with a letter recommending school accommodations, such as taking breaks for symptoms, extra time for assignments, or use of larger print or audio books. The vast majority (95%) of patients seen only in the emergency department were not provided with a letter for school accommodations.

In total, 56.2% of patients received documentation of clearance to return to play or recreational activities. While this may represent the proportion of children participating in organized sports, virtually all of these children are returning to physical activity of some type, like free play or gym class, and therefore all concussed children in this age group would benefit from guidance on how to return to physical activity.

"Children ages 5 to 11 years diagnosed with a concussion had similar rates of visio-vestibular deficits to adolescents and we know that adolescents who have visio-vestibular deficits also have a greater likelihood of persistent symptoms and poorer outcomes," Master said. "Our older youth really benefit from early intervention in the form of school accommodations, return to school and physical activity plans, and vestibular or vision therapy. We believe intervening early can also improve outcomes for younger children diagnosed with visio-vestibular deficits."

Master and her co-authors recommend that clinicians conduct visio-vestibular assessments at the initial health care visit and let the results guide the next steps for concussion management, such as providing a letter or discharge instructions specifying targeted school accommodations, return to physical activity plans and referrals to specialists for patients who have deficits and are therefore at risk of persistent symptoms and longer recovery times. Additionally, the researchers stressed the need to develop proper clinical support tools that aid clinicians in closing the gap to improve early identification and management of these deficits for younger children who have suffered concussions.

For years, researchers have known that men of African ancestry are at greater risk of developing prostate cancer with research suggesting that inherited factors may contribute to their greater risk.

Now, a new USC study published in European Urology is the first to identify an inherited genetic variant associated with higher risk of prostate cancer in men of African descent that contributes to the clustering of prostate cancer cases within families.

"About 12% of men of African ancestry carry this particular variant in the genome, which increases their risk two-fold. The variant is not found in other populations," said Christopher Haiman, ScD, study author and Professor of Preventive Medicine, Keck School of Medicine of USC. "But it's even more common in families with a history of prostate cancer."

African American men at higher risk

One in six African American men develops prostate cancer in his lifetime. African American men are 1.8 times more likely to be diagnosed with - and 2.2 times more likely to die from - prostate cancer than white men. If a black man's brother or father had prostate cancer, his risk will be even higher. But until now, there has been no genetic mutation or biomarker doctors could look for to determine if a particular African American man was more likely to get the disease.

While a prostate specific-antigen (PSA) blood test can detect prostate cancer, many of the cancers it detects may not cause harm, while treatment can cause life-altering side effects.

In the study, which is part of the RESPOND African American prostate cancer initiative, researchers looked at 9,052 prostate cancer cases among men of African ancestry. More than 23 percent had this specific genetic variant. The variant was strongly associated with a prostate cancer diagnosis at an earlier age, more aggressive disease, and men with a family history of prostate cancer. In fact 32 percent of the men with prostate cancer who had a family history of the disease carried the variant.

Variant could aid in screening and treatment decisons

This new information may eventually help clinicians identify men who could benefit from early prostate cancer screening and treatment.

"A man of African ancestry comes in and says, 'Well, I have prostate cancer and I have a family history of the disease. Why?.' Well, now there's a variant you can test to see if they and their family members carry it," said Haiman. "This is a marker that down the road may be used to identify African-Americans and their family members who are at high risk and would benefit from more precise, targeted, and earlier PSA screening."

Researchers believe this variant is one of the reasons why African American men are more likely to get prostate cancer and hope to find out more about the role genetic mutations play in their overall risk.

Patients with raised blood pressure have a two-fold increased risk of dying from the coronavirus COVID-19 compared to patients without high blood pressure, according to new research published in the European Heart Journal [1] today (Friday).

In addition, the study found that patients with high blood pressure who were not taking medication to control the condition were at even greater risk of dying from COVID-19.

Researchers in China and Ireland analysed data from 2866 patients with COVID-19 who were admitted to Huo Shen Shan hospital in Wuhan, China, between 5 February and 15 March 2020. The hospital was opened on 5 February exclusively to treat coronavirus patients. Of these patients, 29.5% (850) had a medical history of high blood pressure (hypertension).

The researchers, led by Professors Fei Li and Ling Tao from Xijing Hospital, found that 34 out of 850 hypertensive patients (4%) with coronavirus died compared to 22 out of 2027 patients without hypertension (1.1%) - a 2.12-fold increased risk after adjustment for factors that could affect the results, such as age, sex and other medical conditions.

Among the patients with hypertension who were not taking medication for the condition, 11 out 140 (7.9%) died from coronavirus compared to 23 out of 710 (3.2%) of those who were taking medication - 2.17-fold increased risk after adjusting for confounding factors.

In a meta-analysis, the researchers pooled the data from the Huo Shen Wan patients with data from nearly 2,300 patients in three other studies to investigate the death rates in patients being treated with drugs to control blood pressure levels by targeting the renin-angiotensin-aldosterone system (RAAS). These drugs include angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). Other, non-RAAS inhibiting drugs used for treating high blood pressure include beta blockers, calcium channel blockers (CCBs) or diuretics.

They found a lower risk of death among the 183 patients treated with RAAS inhibitors than in 527 patients treated with other drugs. However, the researchers say this result should be treated with caution as the number of patients in this analysis was small and so it could be due to chance.

Prof. Li said: "It is important that patients with high blood pressure realise that they are at increased risk of dying from COVID-19. They should take good care of themselves during this pandemic and they need more attention if they are infected with the coronavirus.

"In addition, there were 140 patients admitted to hospital with COVID-19 who had discontinued their anti-hypertensive treatment due to various reasons. We found that this was associated with a greater risk of dying from the coronavirus.

"In contrast to our initial hypothesis, we found that RAAS inhibitors, such as ACE inhibitors or angiotensin receptor blockers, were not linked to an increased risk of dying from COVID-19 and, in fact, may be protective. Therefore, we suggest that patients should not discontinue or change their usual antihypertensive treatment unless instructed by a physician."

Prof. Ling Tao said: "Soon after we started to treat COVID-19 patients in early February in Wuhan, we noticed that nearly half of the patients who died had high blood pressure, which was a much higher percentage compared to those with only mild COVID-19 symptoms. At the same time, some researchers were raising concerns that RAAS inhibitors might be facilitating the entry of the coronavirus into cells and making people more susceptible to the disease.

"We were quite surprised that these results did not support our initial hypothesis; in fact, the results were in the opposite direction, with a trend in favour of ACE inhibitors and ARBs. We think this is exactly why practice based on clinical evidence is more vital than ever."

As this was a study that looked at data from observations in the hospital, the researchers say it is too early to make clinical recommendations based on these results, and that results from randomised controlled clinical trials are needed to look, in particular, at the role played by RAAS inhibitors.

"These data should be interpreted cautiously. However, they support recommendations for the European Society of Cardiology that patients should not discontinue or change their normal, antihypertensive treatment," said Prof. Tao.

As fewer cases of COVID-19 are being diagnosed now in China, a randomised clinical trial is to be run at the National University of Ireland Galway by Professors J. William McEvoy and Patrick Serruys, who are co-authors of the EHJ paper.

Prof. Serruys said: "There are three remaining questions, and we hope our clinical trial in Ireland will answer the first two: what kind of medication should be given to COVID-19 patients with hypertension - RAAS inhibitors or non-RAAS inhibitors - and could these medications mitigate the risk of dying in these patients?

"As for the last question, a recent population-based study in the New England Journal of Medicine [2] has suggested that antihypertensive medications, such as ACE inhibitors and ARBs are not associated with an increased risk of testing positive for COVID-19."

As this is a retrospective, observational study, it cannot show a causal relationship between RAAS inhibitors and the risk of dying from COVID-19. Other limitations include the inability to include all relevant confounding factors; some data, such as electrocardiograms (ECGs) were not recorded in detail; and the impact of antihypertensive medications can only be assessed in the short-term, with prospective studies needed to see longer-term effects.

An editorial about this paper is published in the EHJ at the same time [3].

Humans rely dominantly on their eyesight. Losing vision means not being able to read, recognize faces or find objects. Macular degeneration is one of the major reasons for visual impairment, round the globe, close to 200 million people are affected. Photoreceptors in the retina are responsible to capture the light coming from the environment through the eye. Diseased photoreceptors lose their sensitivity to light, which can lead to impaired vision or even complete blindness. Scientists of the Institute of Molecular and Clinical Ophthalmology Basel (IOB) together with colleagues from the German Primate Center (DPZ) - Leibniz Institute for Primate Research in Göttingen have developed a completely new therapeutic approach based on gene therapy. They managed to activate degenerated photoreceptors using near-infrared light (Science).

The main cause of blindness in industrialized countries is the degeneration of photoreceptors, including age-related macular degeneration and retinitis pigmentosa. During the progression of degenerative photoreceptor diseases, light-sensitive and light-insensitive photoreceptor regions in the retina coexist. For example, macular degeneration patients lose vision in the central portion of their retina but retain peripheral eyesight.

Scientists have now succeeded in developing a new therapeutic approach to restore light sensitivity in degenerating retina without negatively affecting remaining vision. They were inspired by species found in nature, such as bats and snakes, that can localize near-infrared light emitted by the bodies of their preys. This is done by using heat-sensitive ion channels which are able to detect the heat of the near-infrared light. This enables the bats and snakes to superimpose thermal and visual images in the brain and thus react to their environment with greater precision. To equip retinal photoreceptors with near-infrared sensitivity, the researchers devised a three-component system. The first component contains engineered DNA that ensures that the gene coding for the heat-sensitive channel is only expressed in photoreceptors. The second component is a gold nanorod, a small particle, that efficiently absorbs near-infrared light. The third component is an antibody that ensures strong binding between the heat-sensitive channel expressed in photoreceptors and the gold nanorods that locally capture near-infrared light and locally release heat.

The researchers first tested their system in engineered mice with retinal degeneration, confirming that near-infrared light effectively excites photoreceptors and that this signal is transmitted to retinal ganglion cells, the latter representing the output of the retina towards higher visual centers in the brain. Next, they showed that stimulating the mouse eye with near-infrared light is also picked up by neurons in a brain area that is important for conscious vision, the primary visual cortex. They also designed a behavioral test in which untreated blind mice were not able to use near-infrared stimulation to learn a simple task whereas blind mice treated with the three-component system could perform the task related to near-infrared stimulus.

In collaboration with Arnold Szabo, a co-author of the paper and Assistant Professor at the Semmelweis University in Hungary, the researchers could test their new approach on human retinas that can be kept alive in culture medium for months, though blindness sets in a day or so after death by photoreceptors losing their ability to detect light. Experimental results showed that following treatment with the three-component gene therapy method, near-infrared light exposures reactivated the human retina's visual circuitry.

"We believe that near-infrared stimulation is an important step towards providing useful vision to blind patients so that they can regain their ability to read or see faces", says Daniel Hillier, head of the junior research group Visual Circuits and Repair at DPZ, and adds: "We want to give hope to blind people with these findings and will further intensify our research activities in this area here at DPZ within our main project, which focuses on the restoration of vision."

What The Study Did:This study assessed how many pediatric patients presenting for surgery at three tertiary care children's hospitals across the U.S. had COVID-19.

Authors: Apurva S. Shah, M.D., M.B.A., of the Children's Hospital of Philadelphia, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamasurg.2020.2588)

Editor's Note: Please see the articles for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

Treatment of the common disease psoriasis, usually focuses on treating the skin. However, psoriasis patients often have other physical diseases that can bring on depression, anxiety, and suicide. A new study from Umeå University, Sweden, shows that these other somatic diseases have even more impact on patients' mental health than their skin symptoms, highlighting the importance of holistic patient care.

Psoriasis is a lifelong disease. The body produces skin cells too quickly which build up on the skin's surface in the form of inflamed red, painful, itchy scales. Many people with psoriasis have other physical diseases such as being overweight, diabetes and heart diseases.

"What we didn't know before is how psoriasis skin symptoms and other somatic diseases associated with psoriasis impact mental health," says Marcus Schmitt-Egenolf, Dermatologist and Professor at Umeå University.

Previous research found that people with psoriasis suffer more often from somatic and mental diseases compared to individuals without psoriasis. A new study confirmed this. The study also investigated how psoriasis skin symptoms and associated somatic diseases impacted mental health, considering anxiety, depression and suicide together.

The study found that skin symptoms have an important impact on mental health, but that other somatic diseases associated with psoriasis can cause even more harm to mental health.

"We found that skin symptoms increased the risk of mental illness by a third, while other physical illnesses doubled the risk among psoriasis patients," says Kirk Geale, PhD candidate at Umeå University. The results in the study shows a 32 percent increase risk of mental illness caused by skin symptoms and a 109 percent increased risk at other somatic illnesses.

This information is important as the total burden of mental health burden for people with psoriasis, and what contributes to it, was not well established. The study's findings encourage people with psoriasis to talk with their doctors more about symptoms beyond the skin, both physical and mental. It also encourages doctors to proactively discuss these issues with their patients.

"I would be delighted if our study could support the trend towards a more holistic view on psoriasis care. At the doctor's office, lifestyle factors should be discussed in the awareness that individual responsiblity may be limited by available personal and community resources. Such an approach may improve the complete triad of psoriasis - skin symptoms, somatic and mental health alike," concludes Marcus Schmitt-Egenolf.

The study was conducted during 2017 - 2019. Nationwide data from about 100 000 individuals with psoriasis but without earlier mental diseases in Sweden were compared to a control group without psoriasis. The study is published in JAMA Dermatology.

In a time when we have to rely on clinical trials for COVID-19 drugs and vaccines, a new study in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) brings good news about the credibility of registered clinical trials.

The authors are two Bocconi Professors of Economics, Jerome Adda and Marco Ottaviani, and a former MSc student of theirs, Christian Decker, now a PhD candidate at the University of Zurich.

In a clinical trial, statistical significance is a key prerequisite for marketing approval of new drugs. Under a certain threshold of significance, the results of the trial could in fact be due to chance and not to the efficacy of the drug. Given the research costs involved and the lure of large potential profits by the pharmaceutical companies sponsoring the trial, investigators may be pressured to beautify data, a standard argument goes. Previous studies of results of statistical tests reported in scientific journals across a number of disciplines did actually detect an anomalous concentration of significance values immediately above the significance threshold, raising suspicions of selective reporting as well as manipulation.

Adda, Ottaviani and Decker concentrated their attention on the trials registered in ClinicalTrials.gov, the largest registry in the world, and focused on the differences in the results of phase II and phase III trials of the same drug. In phase II a drug's efficacy is initially established in a small sample of people (usually in the low hundreds); in phase III safety and efficacy are then confirmed in a larger group of volunteers (usually in the low thousands). Reasonable expectations are that the statistical significance of phase II will be confirmed in phase III and that trials that record a significance level under the threshold in phase II will be suspended.

Observing all the registered trials, the scholars observe a discontinuity around the significance threshold value only in phase III, but not the spike denounced by previous studies: trials just above the thresholds are only slightly more numerous than expected. They, then, limit their observations to the trials registered by the top-10 pharma companies and by smaller operators. While larger companies are more inclined to suspend experimentation under threshold in phase II, small companies tend to continue with more of the trials under threshold and end up recording a higher share of trials above threshold in phase III. The predicted share of trial results above threshold in phase III for large companies is 65%, and the actually recorded share 68%; with small companies (that bring to phase III also less promising drug candidates), the figures are 57% and 76%.

"Even in the case of phase III trials by small companies", Professor Ottaviani explains, "we do not observe the spike of results just above the significance threshold. We think that the registration process is key for transparency".

New-born piglets often die painfully from infection with an intestinal bacterium. A team of researchers from 3 faculties at the University of Bern has now discovered how the bacterium causes fatal intestinal bleeding. They have thus made a breakthrough in veterinary research. Promising prospects for vaccinations and medications for use in humans too have now opened up.

The Clostridium perfringens bacterium is part of the large Clostridium genus which can cause various fatal illnesses in animals and humans. Clostridium infections are widespread. These bacteria are dangerous because they produce extremely strong poisons (toxins) which cause targeted damage to the host's cells. Dreaded diseases caused by Clostridium include botulism, tetanus, gas gangrene and intestinal infections, for example.

Horst Posthaus's group in the Institute of Animal Pathology at the University of Bern is researching an intestinal infection in pigs which is caused by Clostridium perfringens. 10 years ago, they were already able to demonstrate that the toxin produced by the bacteria, the so-called beta toxin, kills vascular cells and thus causes bleeding in the piglet's intestine. Until now, however, it was unclear why the toxin attacked specifically these cells and not others. Julia Bruggisser, biochemist and doctoral student at the Institute of Animal Pathology, has now succeeded in solving the puzzle of this mechanism in an interdisciplinary collaboration between three faculties. The findings from the study have been published in the specialist journal Cell Host & Microbe.

A key molecule

Around five years ago, lab technician Marianne Wyder from the Institute of Animal Pathology came across a molecule called Platelet-Endothelial Cell Adhesion Molecule-1 (PECAM-1 or even CD31 for short). It is located on the surface of various cells and plays a central role in intestinal bleeding in piglets. The actual role of the CD31 molecule is to regulate the interaction between inflammatory cells and the blood vessels. It predominantly occurs on cells which are located on the inside of blood vessels (so-called endothelial cells).

During experiments, it was noticed that CD31 and the beta toxin are distributed almost identically on these cells. "Our project resulted from this initial observation," says Horst Posthaus. Julia Bruggisser from the Institute of Animal Pathology discovered that the toxin released by the bacteria in the intestine attaches to the CD31. Since the beta toxin numbers among the pore-forming toxins, it thus perforates the cell membrane and kills the endothelial cells. This results in damage to the vessels and bleeding in the intestine.

Researchers at the University of Bern join forces

Collaboration between multiple research groups at the University of Bern was essential for the success of the project. "For my research, I work in three laboratories at the university. Although it's challenging, I learn a lot and above all, it's fun," says Julia Bruggisser. In addition to animal pathology, she also works with groups headed by Britta Engelhardt (Theodor-Kocher Institute) and Christoph von Ballmoos (Department of Chemistry and Biochemistry). "They had the right questions and ideas. We were able to bring our know-how concerning CD31 and methods and reagents which we had developed into the study," says Britta Engelhardt. "It came together perfectly," adds Christoph von Ballmoos.

Better prophylaxis and medications

The discovery makes it possible to develop better vaccines in order to prevent the fatal disease in pigs. "But we also want to investigate whether the attachment of beta toxin to CD31 on the endothelial cells also allows for the development of new forms of therapy, for vascular disease in humans, for example. We have already started more collaborations within the University of Bern to this end," says Horst Posthaus.

This study was supported by the Swiss National Science Foundation (SNSF) and by a grant for international students at the University of Bern.

New Rochelle, NY, June 4, 2020--Next-generation sequencing of the COVID-19 virus is providing powerful metagenomic data, which, combined with clinical data, will inform the search for effective treatments, as reported in the peer-reviewed journal Pediatric Allergy, Immunology, and Pulmonology. Click here to read the article now.

"Continued genomic and epigenomic analysis of SARS-CoV-2 is critical," say Drs. Dehority and Dinwiddie from The University of New Mexico School of Medicine, "as it can be used to determine the number of virus strains, how the virus is introduced into new regions, the number of introductions of the virus, if there is community spread of virus, if outbreaks are linked, and how the virus is evolving."

Genetic analysis will also guide and inform efforts to develop vaccines and both novel and repurposed therapeutic agents, by testing for viral susceptibility or resistance to these interventions.

Pediatric Allergy, Immunology, and Pulmonology Editor-in-Chief Mary Cataletto, MD, Professor of Clinical Pediatrics, Stony Brook University School of Medicine, states that: "As of May 25, 2020, 1,637,456 cases of COVID-19 have been reported to the Centers for Disease Control with 97,669 deaths. The use of these new techniques not only for identification but ongoing surveillance of novel viral pathogens can contribute to early strategic public health responses."

Philadelphia, June 4, 2020--Universally screening pediatric patients for COVID-19 before they undergo surgical procedures has allowed hospitals to improve safety by identifying all patients who test positive for the virus, half of whom have no symptoms, according to new research led by Children's Hospital of Philadelphia (CHOP). The study, which analyzed universal screening procedures at CHOP and two other major children's hospitals, found that screening patients for COVID-19 allowed hospitals to ensure patients and physicians were not exposed to the virus.

The findings were published today in JAMA Surgery.

"CHOP's commitment to screening every patient preoperatively has significantly improved patient safety," said lead author Apurva Shah, MD, MBA, an orthopaedic surgeon in CHOP's Division of Orthopaedics. "Our study shows that many pediatric patients who have COVID-19 are asymptomatic, even though the overall number of positive cases is small, so parents can feel reassured that their children and other children undergoing procedures have been screened for the virus."

The research team, which consisted of physicians from CHOP, Seattle Children's Hospital, and Texas Children's Hospital, gathered COVID-19 screening data on preoperative pediatric patients for one month, from late March to late April 2020. CHOP had begun screening all preoperative patients for COVID-19 on March 26, 2020, as part of its hospital-wide safety procedures. Each of the three hospitals used an in-house, lab-developed reverse transcriptase polymerase chain reaction (RT-PCR) assay to detect COVID-19 in patients with scheduled surgical procedures.

Of the 1,295 patients included in the study, the overall incidence of COVID-19 was 0.93%. However, the researchers found significant variation across hospitals, ranging from 0.22% to 2.65%. Even more striking, at CHOP, 55.56% of positive patients were from a single township, indicating that the incidence in children may vary depending on COVID-19 infection rates in the patients' communities.

Among those pediatric patients who tested positive for COVID-19, half had no symptoms. Of those who did have symptoms, the most common were fever and a runny nose. Nevertheless, the researchers noted symptoms were not useful in differentiating those who tested positive for COVID-19 and those who tested negative.

Given that the study covered a time period when all three hospitals had cancelled elective surgeries, the data reflect pediatric patients who required time-sensitive surgery and thus may not represent the incidence in children undergoing elective surgery. However, the authors say the findings show the value of universal screening in protecting both patients and physicians from COVID-19 exposure in all types of surgery at times when the SARS-CoV-2 virus is actively circulating in a community.

"If a patient tests positive for COVID-19, and the procedure doesn't need to happen immediately, providers can reschedule surgery for a time when the patient has recovered," Shah said. "But in some cases, surgery cannot wait, and in that situation, knowing a patient is positive for COVID-19 allows staff to protect themselves with appropriate personal protective equipment and prevent that patient from coming into contact with other patients and families."

"As we start to relax social distancing measures, and children return to their 'new normal' with exposure to the community, universal testing for children undergoing surgery will be even more important," said first author Elaina E. Lin, MD, an anesthesiologist in CHOP's Department of Anesthesiology and Critical Care Medicine. "As an anesthesiologist that performs many procedures with the highest risk of respiratory virus transmission, I appreciate patients and families partnering with us to keep everyone safe."

FINDINGS

Researchers at the UCLA Jonsson Comprehensive Cancer Center analyzed gene-expression patterns in the most aggressive prostate cancer grade group -- known as Gleason grade group 5 -- and found that this grade of cancer can actually be subdivided into four subtypes with distinct differences. The findings may affect how people are treated for the disease.

One subtype, which accounts for about 15% of the grade group 5 cancers, has highly aggressive features and is associated with much worse outcomes than the other subtypes. Another, which makes up about 20% of the tumors, appears to be much less aggressive and may not require intensified and aggressive treatments. Traditionally, all tumors in Gleason grade group 5 have been treated in the same way.

BACKGROUND

Prostate cancer is the leading solid-tumor cancer among men in the United States and a major cause of morbidity globally. While early-stage, localized prostate cancer is curable, current treatments don't always work for everyone. To find out why standard treatment may work for some and not others, the UCLA researchers looked at tumors in the Gleason grade group 5 subset of prostate cancer. These tumors are at the highest risk to fail standard treatment, leading to metastasis and death. The researchers thought that studying the gene expression -- the unique "signature" -- of each cancer cell in these tumors might provide insight into how to make treatments more personalized for each patient.

METHOD

The researchers first analyzed data from more than 2,100 Gleason grade group 5 tumors, looking at how the genetic blueprints differed among the tumors. They identified distinct clusters of subgroups and validated their findings by analyzing an additional cohort of more than 1,900 Gleason grade group 5 prostate cancers.

IMPACT

By using the genetic information from tumors in men with prostate cancer, physicians hope to one day create more personalized treatments based on the actual characteristics of the cancer. This information will help optimize quality of life and avoid overtreating subgroups of men who may not need aggressive treatments.

AUTHORS

The study's lead author is Dr. Amar Kishan, an assistant professor of radiation oncology at the David Geffen School of Medicine at UCLA and a researcher at the UCLA Jonsson Comprehensive Cancer Center. The co-senior authors are Dr. Joanne Weidhaas, a professor of radiation oncology and director of translational research at the Geffen School of Medicine, and Paul Boutros, a professor of urology and human genetics and director of cancer data science for the Jonsson Cancer Center. Boutros is also a member of the UCLA Institute of Urologic Oncology and the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at UCLA. Other UCLA authors include David Elashoff, Dr. Rob Reiter and Dr. Matthew Rettig.

JOURNAL

The study was published in the journal European Urology.

Nanotechnology has contributed a great deal to the field of medical science. It has enabled researchers to design tools to deliver drugs to specific targets in a living organism. Smart drug delivery vectors, combined with stimuli-based characteristics, are becoming increasingly important. The use of external and internal stimulating factors can have enormous benefits in combination with such drug delivery vectors, as they increase the targeting efficiency of nanotechnology-based platforms. An example of a stimulating factor is the pH of a target cell's surrounding microenvironment. The pH values of tumor vascular tissues are acidic in nature, allowing the improved targeting of anticancer drug payloads using drug-delivery vectors. Nanopolymers are smart drug-delivery vectors that have recently been developed and recommended for use by scientists because of their potential targeting capabilities, non-toxicity and biocompatibility, and make them ideal nanocarriers for personalized drug delivery. This review article provides a summary of current advances in the use of nanoparticles (NPs) as anticancer drug-delivery vectors. It provides information about the molecular basis for the use of NPs in medicine, including personalized medicine, personalized therapy, emerging vistas in anticancer therapy, nanopolymer targeting, passive and active targeting transports, pH-responsive drug carriers, biological barriers, computer-aided drug design, future challenges and perspectives, biodegradability and safety. Researchers, clinicians, and key decision makers in regulatory authorities will benefit from the information provided as it provides a basis for advanced research projects.

Netakimab is a humanized anti-interleukin 17A antibody approved for the treatment of moderate-to-severe plaque psoriasis. Phase three clinical trial PATERA evaluated the effects of netakimab on signs and symptoms of psoriatic arthritis, including disease activity, skin manifestation and quality of life. It included 194 eligible adult patients with psoriatic arthritis who received either 120 mg of netakimab (97 patients in the first treatment arm) or placebo (97 patients in the second arm) subcutaneously during 24 weeks. Baseline demographics and disease characteristics were similar across treatment arms. Patients from placebo arm who did not meet ACR20 (20% improvement of the American College of Rheumatology criteria) by week 16, were switched to 120 mg dose of netakimab.

The results of the clinical trials have shown that 80 patients (82%) in netakimab arm and 9 (9%) in the placebo arm achieved ACR20 at week 24. 70% of patients in netakimab arm achieved ACR50 compared to 6% of patients in placebo arm. As for PsARC (Psoriatic arthritis response criteria) response, it was achieved by 87% of patients in netakimab arm. DAPSA (Disease Activity Index for Psoriatic Arthritis) remission was achieved by 36% in netakimab arm.

As for skin manifestations that negatively affect the quality of life of patients with psoriatic arthritis, 24-week treatment with netakimab at the dose of 120?mg resulted in significant improvement in skin manifestations in patients with psoriatic arthritis: about a half of the patients with ?3% body surface area involvement at baseline achieved complete skin clearance. Netakimab also leads to sustained improvement in axial disease in patients with inflammatory back pain at baseline.

Netakimab was well tolerated, and most adverse effects were mild to moderate. No treatment-related severe adverse effects were reported and no anti-drug antibodies were detected.

Netakimab was registered for treatment of ankylosing spondylitis and psoriatic arthritis in spring 2020 in Russia. According to Phase 3 clinical study BCD-085-5/ASTERA, 40% of patients with ankylosing spondylitis achieve an ASAS40 response after 16 weeks of therapy. The netakimab molecule is based on the llama immunoglobulin which is as close as possible to human immunoglobulins which helps to achieve a sustainable effect from the therapy.

Vaccine Rationing and the Urgency of Social Justice in the Covid-19 Response
Harald Schmidt

While it is unclear when a vaccine will be available for Covid-19, what is clear is that when one has been found, demand will outstrip supply for a period of time and rationing will become necessary. Ethical, epidemiological, and economic reasons demand that rationing approaches give priority to groups that have been structurally and historically disadvantaged, even if this means that overall life years gained may be lower, the author argues. "We must seize the opportunity to allocate vaccines in a way that is both just in the here and now and recognizes the enormous symbolic importance for the collective memory of structurally and historically marginalized groups that comes with being placed first, or last, in line," writes Schmidt, an assistant professor of medical ethics and health policy at the University of Pennsylvania's Perelman School of Medicine. .

Covid-19: Ethical Challenges for Nurses
Georgina Morley, Christine Grady, Joan McCarthy, and Connie. M. Ulrich

The Covid?19 pandemic has highlighted many of the difficult ethical issues that health care professionals confront in caring for patients and families. This essay focuses on the implications for nurses, who are the largest global health care workforce but whose perspectives are not always fully considered. The authors discuss three overarching ethical issues that create a myriad of concerns and will likely affect nurses globally in unique ways: the safety of nurses, patients, colleagues, and families; the allocation of scarce resources; and the changing nature of nurses' relationships with patients and families. The authors urge policy?makers to ensure that nurses' voices and perspectives are integrated into both local and global decision?making so as to minimize the structural injustices many nurses have faced to date. The authors also urge nurses to seek sources of support throughout this pandemic. Morley is a nurse ethicist at the Cleveland Clinic. Grady is a nurse-bioethicist and chief of the Department of Bioethics at the National Institutes of Health Clinical Center. McCarthy is a senior lecturer in health care ethics in the School of Nursing and Midwifery at the University College Cork, in Ireland. Ulrich is a professor of bioethics and nursing at the University of Pennsylvania.