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Leesburg, VA, July 9, 2021--According to ARRS' American Journal of Roentgenology (AJR), reduced-dose CT depicts greater than 90% of lung nodules in children and young adults with cancer, identifying the presence of nodules with moderate sensitivity and high specificity.

"CT performed at 0.3 mSv mean effective dose has acceptable diagnostic performance for lung nodule detection in children and young adults and has the potential to reduce patient dose or expand CT utilization (e.g., to replace radiography in screening or monitoring protocols)," wrote corresponding author Andrew T. Trout of Cincinnati Children's Hospital Medical Center in Ohio.

Trout and colleagues' prospective study enrolled patients 4-21 years old with known or suspected malignancy who were undergoing clinically indicated chest CT. Study participants underwent an additional investigational reduced-dose chest CT in the same imaging encounter. Three independent radiologists blind-reviewed the separated and deidentified CT examinations, with one radiologist performing a subsequent review to match nodules between the standard- and reduced-dose examinations.

Among the 78 patients (44 male, 34 female; mean age, 15.2 years) with cancer who underwent standard-dose chest CT and reduced-dose chest CT (mean effective dose 0.3 ± 0.1 mSv, representing 83% dose reduction) in the same imaging encounter, the reduced-dose protocol detected greater than 90% of lung nodules identified on the standard-dose examination.

Noting that no prior study has directly compared clinical to reduced-dose CT for detection of lung nodules in children, "reduced-dose CT may be a feasible option for detection of pulmonary metastatic disease in situations in which radiation dose is a primary consideration or as an option to reduce dose in patients undergoing serial chest CT to monitor known disease," the authors of this AJR article concluded.

Every pandemic affects life and actions of people, which in turn controls the course of the pandemic. Until now the factors that determine our social, political and psychological sphere could not be described by mathematical models, making it difficult to venture forecasts for the Corona pandemic. The new study will improve the situation. Researcher Prof. Kai Wirtz of the Hereon Institution for Coastal Systems - Analysis and Modeling quantitatively describes the social phenomena hinted at above. "As a scientist, social modeling has been driving me for a while. It has also reached coastal research in the meantime. The greatest challenge in this development was the integration of human agency into conventional epidemiological models," says Wirtz.

How Corona changes people

Due to the problems in predictability of social dynamics, Wirtz uses the uniqueness of the global Corona pandemic for the new study. This comes along with an unprecedented data availability, as he emphasizes. The study uses a part of these data sets - primarily presented by Apple, John Hopkins CSSE und YouGov - to quantitatively test a novel model on the basis of the different pandemic course patterns in 20 affected regions. The regions include 11 EU countries such as Germany, Italy and Sweden, Iran, and eight states in the US.

Societies that were affected by the pandemic at the beginning of 2020, mostly Western industrialized countries, succeeded in curtailing the rates of infection through measures such as social distancing. After the societies began to lift the imposed lockdowns in May 2020, some of them achieved very low case figures while others were affected by an enduring high rate of mortality. Later during the fall and winter seasons of 2020/2021, all these regions were hit by a massive second and third wave despite their experiences made during the first lockdown.

The model of the study combines classic equations for viral spreading with simple rules for social dynamics: as a basis it is assumed that societies act rationally to keep the cumulative damage, resulting from COVID 19-caused mortality and the direct socio-economic cost of social distancing, as low as possible. "However, the simulation results show that another mechanism is crucial to describe the dynamics in the 20 regions: the erosion of so-called "social cohesion" with a reduced willingness for and efficacy of social distancing," says Wirtz.

Lost cohesion

It is only the simulation of this erosion process that results in curves of regional mortality rates and mobility and behavioral changes which are almost exactly identical to the empirical data. Thus, the study presents the first model which increases the period of forecasting from so far few weeks up to one year. In addition, the model can potentially be used to describe the impact of new SARS-CoV-2 mutants.

Based on this study, the regionally diverse second and third waves of the pandemic can be explained as the consequence of differences in social cohesion and climatological factors. The model calculations show that in many countries a Zero Covid-strategy would have been possible in the summer of 2020. "But only if the social fatigue would have been halted and strict travel bans applied," says Kai Wirtz. Due to the successful validation, the model can provide guidance for a medium-term strategic planning, for example, more efficient vaccine distribution. Already at the beginning of 2021 the model predicted for Germany that each delayed day of the mass vaccination causes 178 further Corona deaths on average. With this piece of research, the human approach in dealing with the virus has become better predictable.

ATLANTA--The American College of Rheumatology (ACR), in partnership with the Vasculitis Foundation (VF), released three new guidelines for the treatment and management of systemic vasculitis. Vasculitis is a group of about 20 rare diseases that have inflammation of blood vessels in common, which can restrict blood flow and damage vital organs. The three guidelines cover six forms of vasculitis, and a fourth guideline on Kawasaki disease will be released in the coming weeks.

"Many rheumatologists may have limited experience caring for patients with these diseases," said Dr. Sharon Chung, Director of the Vasculitis Clinic at the University of California, San Francisco, and the lead investigator of the guidelines. "However, the treatment options for patients with vasculitis have expanded in recent years. Thus, these guidelines provide practitioners evidence-based recommendations to help navigate the treatment path for their patients."

The guideline for giant cell arteritis (GCA) and Takayasu arteritis (TAK), both forms of large vessel vasculitis, provides a total of 42 recommendations and three ungraded position statements. The recommendations and statements address clinical questions relating to the use of diagnostic testing (including imaging), treatments, and surgical interventions in GCA and TAK. Recommendations for GCA support the use of glucocorticoid-sparing immunosuppressive agents and the use of imaging to identify large vessel involvement. Recommendations for TAK include the use of non-glucocorticoid immunosuppressive agents with glucocorticoids as initial therapy.

The guideline for polyarteritis nodosa (PAN), a medium vessel vasculitis, provides a total of 16 recommendations and one ungraded position statement. The recommendations support early treatment of severe PAN with cyclophosphamide and glucocorticoids, limiting toxicity through minimizing long-term exposure to both treatments, and the use of imaging and tissue biopsy for disease diagnosis. The recommendations endorse minimizing risk to the patient by using established therapy at the start of the disease and identify new areas where adjunctive therapy may be warranted.

The guideline for antineutrophil cytoplasmic antibody-associated vasculitis (AAV), a small vessel vasculitis, provides a total of 41 recommendations and 10 ungraded position statements for granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). According to the VF, the overall, worldwide incidence of AAV ranges from 0.5.-20 cases per 1 million people. In children, the incidence ranges from 0.45-6.4 cases per 1 million children per year. The guideline provides recommendations for remission induction and maintenance therapy as well as adjunctive treatment strategies in GPA, MPA, and EGPA. The recommendations include the use of rituximab for remission induction and maintenance in severe GPA and MPA and the use of mepolizumab in non-severe EGPA.

These new guidelines are the first produced and endorsed by the ACR and the VF. The organizations hope the guidelines will help providers better understand and treat the various forms of vasculitis.

"Different forms of vasculitis can have similar symptoms and treatment regimens; however, each disease is distinct, "said Joyce Kullman, Executive Director of the Vasculitis Foundation. "These guidelines will hopefully take some of the guesswork out of determining which treatments might work best for newly diagnosed patients, or patients who have been under treatment for a while without success."

As much as the guidelines highlight what evidence-based knowledge exists for the treatment and management of vasculitis, they also shine a light on what work needs to be done.

"We identified knowledge gaps that would benefit from additional research, like comparative effectiveness trials, longitudinal studies of imaging modalities, and identification of biomarkers to inform disease activity assessments," said Dr. Chung. "We hope this fuels research in these areas to facilitate patient care."

Like many other ACR guidelines, the three guidelines for vasculitis were developed using Grading of Recommendations Assessment, Development and Evaluation?(GRADE) methodology, which creates rigorous standards for judging the quality of the literature available and assigns strengths to the recommendations. Most of the recommendations in the guidelines are conditional because of the rarity of these diseases. The papers containing the full list of recommendations and supporting evidence is available at on the ACR website.

New research presented at this year's European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) shows the importance of receiving the second dose of a COVID-19 vaccine and also the need to constantly review and update vaccines to deal with new variants of concern. The study is by Dr Nicole Schneiderhan-Marra, Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany, and colleagues.

While vaccines have begun to bring the pandemic under control in certain countries, it remains unclear how effective these vaccines will continue to be as the virus mutates and evolves. The protection generated against the virus by vaccination is normally measured by antibodies, with a certain group called "neutralising antibodies" being of particular importance, as they defend the body and destroy the virus.

As the current generation of vaccines were all designed against the original virus strain (known as the "wild type"), they offer maximum protection against this strain. However, it remains unclear whether the protection will still be the same against new strains of the virus, such as the alpha (Kent/ UK), beta (South Africa) delta (India) or gamma (Brazil) variants.

To see how the protection offered by the vaccine changed for different variants, the researchers firstly profiled the antibodies generated by vaccination and then examined their neutralising capacity. In addition to antibodies circulating within the blood, they checked for the presence of antibodies in saliva as a "first line of defence".

To do this, they adapted a previously developed assay that measures the antibodies present against SARS-CoV-2 and other coronaviruses in the blood, to include targets from variants of concern and to look specifically at the neutralising antibodies. They collected samples from 23 vaccinated individuals (age 26-58 years, 22% female) who had been vaccinated with Pfizer BioNTech vaccine after the first and second doses. For control groups, the team also collected samples from 35 infected blood donors (age 40-78 years, 29% female) 27 infected saliva donors (age 25-58 years, 63% female) and 49 non-infected saliva donors (age 25-38 years, 55% female) and also control samples of blood and saliva sourced commercially from before the pandemic began.

When looking at the saliva, they saw that vaccinated individuals had large amounts of antibodies present compared to infected individuals, suggesting that vaccination not only offers protection against becoming infected, but should you become infected, it reduces the possibility of you transmitting it to others.

The number of antibodies produced and protection offered by vaccination increased substantially after the second vaccine dose was given, showing the importance in receiving the second dose. At the time of the study, the two global variants of concern were the alpha and beta variants, so they examined whether the protection offered against these two variants was similar or different to that offered against the "wild-type". They found that while there was no reduction in neutralising antibodies against the alpha variant, there was a substantial reduction in neutralising antibodies against the beta variant. "This shows the importance of constantly updating vaccines to offer maximum protection against different strains of the virus," explains Dr Schneiderhan-Marra.

Since this study was completed, the virus has continued to mutate, with the delta variant now the dominant strain globally. As a result, the researchers have further developed their assays to include more targets from variants of concern, such as delta (India) and gamma (Brazil), along with other variants of interest (eta, iota, zeta, theta, kappa and epsilon), and other interesting strains such as the mink mutation discovered last year.

Dr Schneiderhan-Marra says: "Two further questions remain however with regards to vaccination: firstly, what protection is offered by the current vaccines against the delta and any other variants that arise in the future, and secondly, how long does protection offered by the current vaccines last and will you need a booster shot to not only increase protection generally, but to also offer protection against new variants?"

Her team is working on various studies, one of which includes the same donors in this study and how the protection they received from the vaccine changes over the course of the year. A further study is looking at how neutralising antibodies differ between different vaccines, and finally other studies are looking into other variants and their impact on protection.

By Karina Toledo | Agência FAPESP* – A study conducted at the University of São Paulo (USP) in Brazil shows that the incidence of infections by the novel coronavirus among professional soccer players in São Paulo state during the 2020 season was 11.7%, the same as among health workers in the front line of the response to the pandemic.

To arrive at this number, the researchers retrospectively analyzed almost 30,000 RT-PCR tests performed on swabs from 4,269 athletes during eight tournaments of the São Paulo State Soccer Federation (FPF), the league responsible for organizing official championships in the state – six for men (the São Paulo Cup, Under-23s, U-20s, and the three divisions of the São Paulo Championship) and two for women (the São Paulo Championship and U-17s). A total of 501 tests confirmed the presence of SARS-CoV-2. They also analyzed 2,231 tests on swabs from support staff (health workers, technical committees, directors, kitmen, etc.), and 161 (7%) were positive.

“It’s a much higher attack rate than has been seen in other countries. In Denmark, for example, only four out of 748 players tested positive [0.5%]. The Bundesliga [in Germany] found eight cases out of 1,702 players [0.6%]. Even in Qatar, where there’s a moderate risk of community transmission, the rate was far lower than ours: 24 out of 549 tested positive [4%]. Compared with the other reported rates, our players were infected between three and 24 times more,” Bruno Gualano, a professor at the University of São Paulo’s Medical School (FM-USP) and principal investigator for the study, told Agência FAPESP.

In an article published in the British Journal of Sports Medicine, the authors say the numbers are probably underestimated. The group had access to the database of the laboratory commissioned by FPF to test the athletes. However, players belonging to clubs that competed in national tournaments could choose to be tested by laboratories commissioned by the Brazilian Soccer Confederation (CBF), and these results were not included in the analysis.

In any event, the São Paulo data shows that the virus affected men and women equally among those tested. A comparison of the results for players and staff shows a high attack rate among players, but severe cases of COVID-19 were more frequent among staff, who are older on average and are not all in perfect health.

“This is a cause of concern,” Gualano said. “The few severe cases, one of which ended in death, were reported among members of staff. Although our data suggest players tend to manifest only mild symptoms or none at all, they can of course transmit the virus to others in the community. Most have a very active social life.”

Contact tracing has never been implemented in Brazil as a public health policy, he added, so it is not possible to measure the impact of the secondary infections caused by players in their households or social circles.

Risk factors

Owing to the social distancing measures implemented in the state of São Paulo in March 2020, soccer matches were temporarily suspended and resumed only on June 14. To minimize the risk of viral transmission, FPF’s Medical Committee created a protocol that calls for frequent testing of players and support staff, isolation of all infected individuals, contact tracing (within the sports community), and routine hygiene practices.

“Cases appeared whenever the protocol wasn’t followed,” said Moisés Cohen, who chairs the Medical Committee. “It’s a controlled environment where risks are monitored and minimized, including testing every two to three days. Players who leave [the isolation bubble] and return are tested every day. We also trace the contacts of individuals with positive test results and follow best practices in terms of protection, such as using PPE [personal protective equipment] and hand hygiene,” he said.

According to Gualano, the risk of viral transmission during matches has proved low, but other factors impair the efficacy of the protocol, which he considers technically adequate. “It would work well if applied in Denmark or Germany,” he said. “It depends significantly on the common sense of the players, who are required to go straight home from the training center and maintain social distancing and non-pharmacological measures when resting. Here in Brazil, however, a sizable proportion don’t follow the rules and aren’t penalized at all. In addition, players and staff travel to and from fixtures a good deal. The smaller clubs travel by bus, eat at restaurants, and are probably more exposed than elite players. Our social inequality is also true of soccer.”

The study shows that some clubs were far more affected than others. One club reported 36 positives, with 31 occurring in a single month. Seven clubs had more than 20 confirmed cases and 19 had ten or more. For Cohen, all outbreaks are due to non-compliance with the protocol.

Gualano expressed strong concern over the resume of São Paulo Championship fixtures after suspension of all matches in São Paulo state on March 11, in response to the sharp rise in hospitalizations and deaths and the emergence of more aggressive viral variants. The suspension was lifted on April 10; nonetheless, matches during this period were taking place at Volta Redonda, a nearby city in Rio de Janeiro state.

“Until the transmission of COVID-19 is mitigated, any sector that reopens represents a high risk of contagion,” Gualano said. “The only safe option would be to isolate the entire soccer sector inside a bubble, which is what the NBA [the National Basketball Association in the United States] did at a cost of USD 170 million. Either shut down or isolate.”

The study was conducted under the auspices of Sports-COVID-19, a coalition of researchers affiliated with FM-USP’s hospital complex (Hospital das Clínicas), the Albert Einstein Jewish-Brazilian Hospital (HIAE), the São Paulo Heart Hospital (HCor), the Niterói Hospital Complex, the Federal University of São Paulo (UNIFESP), the Dante Pazzanese Institute of Cardiology, and the São Paulo Center for Research on High-Performance Sports (NAR-SP), with FPF’s support. The consortium aims to investigate the long-term consequences of COVID-19 for soccer players and other elite athletes.

Besides Gualano and Cohen, the article’s authors include two holders of PhD scholarships from FAPESP: Ana Jéssica Pinto and Ítalo Ribeiro Lemes.

The Delta variant was detected for the first time in India in October 2020 and has since spread throughout the world. It is now dominant in many countries and regions (India, the UK, Portugal, Russia, etc.) and is predicted to be the most prevalent variant in Europe within weeks or months. Epidemiological studies have shown that the Delta variant is more transmissible than other variants. Scientists from the Institut Pasteur (CNRS joint unit), in collaboration with Hôpital Européen Georges Pompidou (part of the Paris Public Hospital Network or AP-HP), Orléans Regional Hospital and Strasbourg University Hospital, studied the sensitivity of the Delta variant to monoclonal antibodies used in clinical practice to prevent severe forms of the disease in people at risk, as well as to neutralizing antibodies in the sera of individuals previously infected with SARS-CoV-2 or vaccinated. They compared this sensitivity with that of the virus previously circulating in France (known as the Alpha or "British variant") and the "South African variant" (Beta variant). The scientists demonstrated that the Delta variant is less sensitive to neutralizing antibodies than the Alpha variant. Three of the four therapeutic monoclonal antibodies tested are effective against the Delta variant, but one of them (Bamlanivimab) loses its antiviral activity. The scientists demonstrated that sera from convalescent patients collected up to 12 months post symptoms were 4 fold less potent against the Delta variant, relative to the Alpha variant. They also studied sera from people vaccinated with two doses of the Pfizer or AstraZeneca vaccine: their sera effectively neutralized the Delta variant, although efficacy was slightly lower than against the Alpha variant. Sera from individuals who had received a single dose of vaccine (Pfizer or AstraZeneca) were inactive or barely active against the Delta and Beta variants. In summary, the Delta variant is slightly more resistant to neutralizing antibodies than the Alpha variant. The study was published as a preprint on the bioRxiv website on May 28, 2021 and published in the July 8th, 2021 issue of Nature.

Epidemiological studies demonstrate that the Delta variant is approximately 60% more transmissible than the Alpha variant. The Delta variant's biological characteristics are still relatively unknown. It is characterized by the presence of nine mutations in the Spike protein and has been designated a "Variant of Concern" by several public health organizations including WHO.

In the United Kingdom, for example, the number of cases diagnosed has risen in recent weeks. Between June 23 and 30, 2021, 135,000 people tested positive, with the Delta variant representing 70-90% of sequenced viruses. Two months ago, most cases were imported from India, but a significant rise in the number of indigenous cases has been observed since mid-April.

In France, the Delta variant accounted for over 20% of new cases in the last week of June, compared to 9% the previous week.

In a new study, scientists from the Institut Pasteur, in collaboration with Hôpital Européen Georges Pompidou (part of the Paris Public Hospital Network or AP-HP), Orléans Regional Hospital and Strasbourg University Hospital, examined the sensitivity of the Delta variant to antibodies compared with the strains circulating in France and other variants referred to as the British (Alpha) and South African (Beta) variants. The aim of the study was to characterize the efficacy of therapeutic antibodies, as well as antibodies developed by individuals previously infected with SARS-CoV-2 or vaccinated, to neutralize this new variant.

The scientists isolated SARS-CoV-2 variant Delta from a nasal sample of a patient who developed COVID-19 a few days after returning from India in April 2021. Therapeutic monoclonal antibodies and serum samples from people who had been vaccinated or previously exposed to SARS-CoV-2 were used to study the sensitivity of the variant to neutralizing antibodies.

"We isolated an infectious strain of the Delta variant and used a novel semi-automated rapid neutralization assay developed in our laboratory. This collaborative multidisciplinary effort involved the Institut Pasteur's virologists and specialists in the analysis of viral evolution and protein structure, together with teams from Hôpital Européen Georges Pompidou and the hospitals in Orléans and Strasbourg. We demonstrated that this variant, which spreads more rapidly, has acquired partial resistance to antibodies. For example, the sera of patients previously infected with COVID-19, collected up to 12 months after they experienced symptoms, and of individuals who had received two doses of the Pfizer or AstraZeneca vaccine are still neutralizing but are three to six fold less potent against the Delta variant as compared with the Alpha variant. And the sera of individuals vaccinated with a single dose of the Pfizer or AstraZeneca vaccine are relatively or completely ineffective against the Delta variant," continues Olivier Schwartz, co-last author of the study and Head of the Virus and Immunity Unit (Institut Pasteur/CNRS).

The scientists also demonstrated that one therapeutic antibody, Bamlanivimab, no longer functions against this strain, although Etesevimab, Casirivimab and Imdevimab remain active.

The scientists concluded that the mutations in the Spike protein of the Delta variant potentially modify virus binding to the receptor and allow partial escape from the immune response. Ongoing studies are now focused on understanding why this variant is more transmissible.

A survey offered to transgender and nonbinary people across six continents and in thirteen languages shows that during the first months of the COVID-19 pandemic, many faced reduced access to gender-affirming resources, and this reduction was linked to poorer mental health. Brooke Jarrett of the Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, and colleagues present the findings in the open-access journal PLOS ONE on July 9.

Gender-affirming resources, which can include health care such as surgery and/or hormone therapy as well as gender affirming services and products --are well-known to significantly boost mental health and quality of life for transgender and nonbinary people. However, factors such as transphobia, lack of proper clinician training, and individual economic insecurity can hamper access to such resources.

Meanwhile, mounting evidence suggests that measures to reduce the spread of COVID-19 exacerbated these challenges. For instance, people may have had to cancel gender-affirming surgeries that were perceived to be elective. Or they may have had to move in with unsupportive relatives and spend more time living according to their sex assigned at birth instead of their actual gender.

To better understand the worldwide impact of the COVID-19 crisis on transgender and nonbinary people, Jarrett and colleagues surveyed 964 adults residing in 76 countries via the social networking apps Hornet and Her. The survey, conducted between April and August 2020, asked participants questions about how the pandemic had affected their access to gender-affirming resources, mental health, and financial stability.

Statistical analyses of the survey responses showed that about half of the participants faced reduced access to gender-affirming resources during the study period. Nearly 40 percent said that the pandemic reduced their ability to live according to their gender. Many also reported anticipating financial hardships, such as possible reduced income and possible loss of health insurance. Those who reported reduced access to gender-affirming resources also had increased prevalence of depressive symptoms, anxiety, and suicidal ideation.

The researchers say that their findings highlight a need to increase and secure access to gender-affirming resources in order to improve the health of transgender and nonbinary people, during and beyond the COVID-19 pandemic.

The authors add: "Transgender communities, who already face a myriad of health inequities, experienced even further health burdens due to restrictions imposed during COVID, like reduced access to gender-affirming treatments and mental health resources. To move forward, we need to support trans communities with policies that make gender-affirming healthcare affordable, accessible, and recognized as essential."

Growth impairment, a common complication of Crohn's disease in children, occurs more often in males than females, but the reasons are unclear. Now, a physician-scientist from Weill Cornell Medicine and NewYork-Presbyterian and colleagues at eight other centers have found that factors associated with statural growth differ by sex. Their recent publication, identified as the "Editor's Choice / Leading Off" article and receiving a mention on the cover of the June issue of Inflammatory Bowel Diseases, underscores the need for investigating and developing sex-specific treatment strategies for children with Crohn's disease, an approach that is not currently part of the pediatric Crohn's disease management algorithm.

The Growth Study is an ongoing prospective, multicenter, longitudinal cohort study investigating sex differences in growth impairment in children with Crohn's disease. For their current analysis, lead author Dr. Neera Gupta, principal investigator for The Growth Study, director of research for the Pediatric Inflammatory Bowel Disease (PIBD) Program and an associate professor of pediatrics at Weill Cornell Medicine and a pediatric gastroenterologist at NewYork-Presbyterian Komansky Children's Hospital, and colleagues examined a range of variables associated with statural growth by sex for 113 children with Crohn's disease, such as disease characteristics, patient-reported symptoms at onset and the use of certain medications.

Among 41 female patients, an initial classification of IBD as Crohn's disease or perianal disease at diagnosis were associated with better growth. However, patient-reported joint pain at symptom onset or the use of probiotics or azathioprine/6-mercaptopurine were associated with worse growth.

Variables associated with statural growth were markedly different for 72 male patients. Patient-reported poor growth at symptom onset or the use of infliximab, biologics, methotrexate or vitamin D were associated with better growth. In contrast, an initial classification of IBD as Crohn's disease or patient-reported anorexia or mouth sores at symptom onset were associated with worse growth.

The authors noted that female patients appear to grow better independent of disease severity/inflammatory burden and medication interventions. Their findings suggest sex-specific molecular pathways lead to growth impairment in children with Crohn's disease, and that there may be a difference in the response of these sex-specific molecular pathways to current medications used to treat pediatric Crohn's disease. Sex will likely be an important future determinant of treatment decisions, which will represent a major advancement in clinical decision making for pediatric Crohn's disease.

"Through the Growth Study, we aim to transform the care of pediatric patients with Crohn's disease by providing an evidence-based approach for the appropriate early introduction of aggressive therapy in patients with high risk for each sex because there is only a narrow therapeutic window available for intervention to improve statural growth," the authors wrote.

Should we delay covid-19 vaccination in children?

The net benefit of vaccinating children is unclear, and vulnerable people worldwide should be prioritised instead, say experts in The BMJ today.

But others argue that covid-19 vaccines have been approved for some children and that children should not be disadvantaged because of policy choices that impede global vaccination.

Dominic Wilkinson, Ilora Finlay, and Andrew Pollard say for a health system to offer any vaccine to a child, two key ethical questions must be asked. First, do the benefits outweigh the risks? Second, if the vaccine is in short supply, does someone else need it more?

"Careful attention to both questions suggests that we should not yet roll out covid-19 vaccination to otherwise healthy children."

They acknowledge that in older adults, the benefits of covid vaccines clearly outweigh the rare side effects. And in children with certain chronic or acute serious illnesses they probably do, and these children should therefore have access to a vaccine. "But in otherwise healthy children, no one can currently be sure."

But they say one thing we can be sure of is that in the UK, some people are currently at much higher risk from covid-19 than healthy children. And most lower income countries have fully vaccinated less than 5% of their community.

Some might ask, why do we have to choose? Can't we vaccinate children as well as those overseas? But, to put it simply, there are right now a limited number of vaccine doses.

"As adults, we have had to wait our turn for the vaccine. We have understood that, given its scarcity, the vaccine has to be prioritised for people at the highest risk of dying." This clear and inescapable ethic now applies to our children, they conclude. Their turn will come--but not yet.

But Lisa Forsberg and Anthony Skelton say that vaccinating children against covid-19 protects them - and others - from the risk of harm and death from infection, and it is the best way to promote children's wellbeing by minimising need for restrictions or disruptions to their lives resulting from failure to properly manage infection spread.

They say the argument that children are less likely to be severely harmed by covid-19 infection, and they therefore benefit less from a vaccination protecting them from it, is mistaken.

"It exposes children to unknown risks of severe disease and of long term health complications. Moreover, we now know that exposing children to those risks disproportionately harms already disadvantaged children."

Another argument for delaying the vaccination of children is that priority should be given to older adults in developing countries where vaccine supply has been limited.

Yet they point out that currently global vaccine supply shortages result from policy choices.

"The ethically defensible choice is to exert whatever pressure we can to minimise vaccine hoarding and distribute vaccines to developing countries, while releasing patents and allowing the manufacture and supply of vaccines at a larger scale, to enable vaccination of adults and children everywhere," they write.

They believe that accepting the "austerity" narrative that children must wait until the most vulnerable people in other countries can be vaccinated diverts focus from the real problem: that profits are valued over lives. "Here, as elsewhere, we are failing in our responsibilities to avoid aggravating existing injustice," they conclude.

Externally peer reviewed? No

Evidence type: Debate; Argument

Subjects: Children; Covid-19 vaccination

*Note: this paper is being presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) and is being published in The Lancet Rheumatology. Please credit both the congress and the journal in your stories*

A new study presented at this year's European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) and published in The Lancet Rheumatology, shows that the antibody - but not the T-cell - response to the first dose of the Pfizer COVID-19 vaccine is weakened in patients taking the immunosuppressant methotrexate. In contrast, antibody and T cell responses are preserved in patients taking biological drugs such as tumour necrosis factor (TNF) inhibitors.

Around 3% to 7% of people in Europe and North America have immune-related inflammatory diseases such as psoriasis, rheumatoid arthritis, and inflammatory bowel disease. Treatments such as methotrexate, TNF inhibitors, and other targeted biological therapies work by suppressing the immune system and, while they can be highly effective, they can also increase the risk of serious infections.

Patients taking immunosuppressants for immune-mediated inflammatory diseases were excluded from COVID-19 vaccine trials, so there is a lack of data on how well they work in this vulnerable group.

Assessment of immune responses to a single dose of vaccine is particularly important given that many countries, including the UK, have extended the interval between doses to maximise population coverage.

Dr Satveer Mahil, Professor Catherine Smith and colleagues at St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust, London, UK and King's College London, enrolled 101 participants from January 14 2021 to April 4 2021 (84 patients with the skin condition psoriasis and 17 healthy volunteers). The participants' median age was 43, 55% were male, 84% were of White ethnicity, and none had had COVID-19 previously.

The psoriasis patients were taking methotrexate (17 patients, median dose of 15 mg/week), TNF inhibitors (27 patients), interleukin (IL)-17 inhibitors (15 patients) or IL-23 inhibitors (25 patients).

Immune responses were measured immediately before being given a single dose of the Pfizer vaccine and 28 days later. The primary outcomes were humoral immunity (neutralising antibody response) to the wild-type SARS-CoV-2 virus and T-cell response 28 days after vaccination.

Rates of seroconversion (the development of antibodies against the virus) were lower in the patients on immunosuppressants. All 17 (100%) healthy volunteers had evidence of seroconversion, compared with 78% of those on immunosuppressants. The lowest seroconversion rate, 47%, was in patients taking methotrexate.

Levels of neutralising antibodies, antibodies able to stop the virus from entering cells, were significantly lower in patients taking methotrexate compared to healthy controls but were preserved in those taking biologics.

T-cell responses were detected in all groups at similar rates and levels, and many participants without evidence of seroconversion showed a T-cell response.

Levels of neutralising antibodies to the B.1.1.7 (Alpha) variant were also tested. These were similarly low in all participants (including healthy volunteers), underlining the need to continue to take preventative measures after having a first dose of the vaccine.

Data on the participants' response to the second dose are awaited.

The authors say: "While global mass COVID-19 vaccination programmes are underway, there remains concern over vaccine efficacy in immunocompromised patients, including against novel SARS-CoV-2 variants that threaten immune escape."

"Measures of the immune response that correspond to decreased risk of COVID-19 after vaccination are unknown, and emerging research in immunocompromised patients has focused on seroconversion alone. We show that serological responses are not representative of the complex immune response to vaccines."

"Our data showing that the T-cell responses following the first dose of the Pfizer COVID-19 vaccine were not affected in those taking methotrexate or a biologic therapy - including in some of those who didn't seroconvert - is reassuring. However, ongoing monitoring of these patients is needed to determine what this means for the clinical effectiveness of the vaccines."

HOUSTON - Researchers from The University of Texas MD Anderson Cancer Center found specific intestinal microbiota signatures correlate with high-grade adverse events and response to combined CTLA-4 and PD-1 blockade treatment. The study, published today in Nature Medicine, also identified a potential new strategy to treat toxicity - while maintaining response - to combined immune checkpoint blockade through either IL-1R inhibition or manipulation of the gut microbiota.

Dual immune checkpoint therapy has contributed to progress in overall survival for many cancer types, including advanced melanoma. Combining CTLA-4 and PD-1 inhibitors produces high responses, yet is often accompanied by immune-related adverse events, such as colitis, an inflammatory bowel disease that can cause additional complications. The field is currently lacking strong biomarkers to understand which patients are most likely to respond to combined checkpoint inhibitors and which patients are most likely to develop severe toxicity to the treatment.

"This study further highlights the importance of the gut microbiome in both response as well as in toxicity in patients being treated with combined immune checkpoint blockade," said senior author Jennifer Wargo, M.D., professor of Genomic Medicine and Surgical Oncology. "We're committed to understanding and addressing the significant immune-related side effects that tend to accompany this combination therapy, so that patients don't have to compromise quality of life for effective cancer treatment."

The study found a significantly higher abundance of Bacteroides intestinalis in the gut microbiota of patients with advanced melanoma who experienced toxicity from combined immunotherapy. In both patients and preclinical models, a high abundance of B. intestinalis in the gut microbiota was affiliated with increased mucosal IL-1β and associated inflammation. Inhibiting IL-1R with a drug approved to treat rheumatoid arthritis reduced intestinal inflammation without blunting the efficacy in pre-clinical models.

Another bacterium, Parabacteroides distansonis, was associated with response to treatment in both the patient cohort and preclinical models. Gut microbiome diversity wasn't significantly different between responders and non-responders, contrary to previous research focusing on single-agent immune checkpoint blockade targeting PD-1.

The patient cohort was comprised of 77 adults who received combined CTLA-4 and PD-1 blockade treatment for advanced melanoma at MD Anderson. The majority had stage IV disease (84%) and had not received any previous systemic therapy (74%). Nearly all patients had an adverse event of any grade (93.5%) and about half (49%) experienced grade 3 or higher adverse events in response to treatment.

Immune and genomic biomarkers

The research team also studied genomic and immune predictors of response to combined immune checkpoint blockade and identified some associations between immune cell profiles in the blood and toxicity to treatment. Patients who experienced grade 3 or higher adverse events had a more diverse T cell repertoire and a more naïve T cell phenotype in the systemic circulation.

Whole-exome sequencing of 26 pre-treatment cutaneous melanoma tumor samples revealed higher tumor mutational burden (TMB) in responders, compared to non-responders. Non-responders had a higher level of copy number loss, primarily affecting chromosomes 5, 10 and 15. These findings further support previous studies that suggest TMB is associated with response and copy number loss is associated with resistance. Baseline tumor biopsies also revealed a higher density of CD8+ T cells in responders, compared to non-responders.

These results also support previously identified immune and genomic biomarkers for response to treatment with a single immune checkpoint blockade.

Additional studies in larger cohorts will be required to validate the biomarkers for toxicity and response, to further understand the underlying mechanisms and to investigate IL-1R inhibition as a potential therapeutic target for inflammation.

"We're getting closer to understanding which patients are most likely to benefit from checkpoint inhibitors and to identifying strategies to mitigate toxicity," Wargo said. "We're grateful to the patients who have participated in our ongoing research; they continue to motivate and inspire us as we undertake additional studies to build upon the insights from this research."

Reston, VA--A performance evaluation of the uEXPLORER total-body PET/CT scanner showed that it exhibits ultra-high sensitivity that supports excellent spatial resolution and image quality. Given the long axial field of view (AFOV) of the uEXPLORER, study authors have proposed new, extended measurements for phantoms to characterize total-body PET imaging more appropriately. This research was published in the June issue of The Journal of Nuclear Medicine.

uEXPLORER is the world's first commercially available total-body PET scanner. The scanner has an AFOV of 194 cm, which allows PET data collection from the entire human body simultaneously and greatly increases PET scanner sensitivity.

Characterization of positron emission tomography (PET) scanners has commonly followed the National Electrical Manufacturers Association (NEMA) NU 2-2018 standard, which defines a set of experiments and analyses using standardized imaging phantoms. This permits valid comparisons between different PET systems. In this study, researchers utilized phantoms to assess the uEXPLORER's sensitivity, count-rate performance, time-of-flight resolution, spatial resolution, image quality and accuracy of corrections based on NEMA NU 2-2018 standards. Human studies were also conducted for further characterization.

"Our results with the uEXPLORER PET/CT system show a major gain in sensitivity compared to conventional PET systems, approximately 15 to 68-fold higher than others," noted Eric Berg, PhD, project scientist in biomedical engineering at the University of California, Davis. "We documented excellent spatial resolution that is well supported by the increased image signal to noise ratio. Additionally, post-reconstruction image smoothing was unnecessary in both phantom and human imaging studies."

Although the NEMA NU 2-2018 measurements were performed in this characterization of the uEXPLORER scanner, these standards are defined only for PET scanners with an AFOV of no more than 65 cm and are not well suited for long-AFOV scanners, like the 194-cm-long uEXPLORER. As part of the study, researchers devised a set of additional informative phantom measurements that to evaluate uEXPLORER more accurately for total-body PET imaging.

"This work provides a benchmark for testing the performance of long axial field of view scanners, which are set to revolutionize the capabilities of PET scanning. Understanding their performance is essential for improving the quality of scans, scanning more quickly, scanning with lower activity, or scanning much later after radiotracer injection," said Ramsey D. Badawi, PhD, vice-chair for research in the department of radiology at the University of California, Davis.

He continued, "These capabilities have the potential to significantly improve patient care in all the areas where PET is currently used, and in addition in new areas, such as autoimmune disease, metabolic disease and other chronic conditions where historically dose considerations have excluded it's use."

Firearm purchases and firearm violence surged dramatically during the first five months of the COVID-19 pandemic, according to a new study from the UC Davis Violence Prevention Research Program (VPRP), published in Injury Epidemiology.

From March through July 2020, an estimated 4.3 million more background checks for firearm purchases occurred nationwide than would have ordinarily — an 85 percent increase. The total number of firearm purchases during this period was 9.3 million.

From April through July 2020, there was a 27% increase in interpersonal firearm injuries, which includes firearm homicides or nonfatal firearm assault injuries. This is approximately 4,075 more injuries than would be expected for that period.

Firearm violence is a significant public health problem in the United States. It is among America’s leading causes of death and disability and has profound adverse social, psychological and economic effects.

“Early in the pandemic, there were news reports about an increase in firearm purchasing. Given what we know about the risks of firearm violence associated with firearm access in general, and firearm purchasing surges specifically, we expected to see a relationship between these two during the pandemic,” said Julia Schleimer, lead author for the study and a research data analyst at VPRP.

States with the most excess firearm purchases per 100,000 population (March–July 2020)

1. Mississippi 2804.8
2. Wyoming 2632.7
3. Alabama 2506.8
4. Idaho 2386.2
5. Michigan 2385.7

Firearm purchases and domestic violence

An earlier study from VPRP had found an association between firearm purchases and violence through May 2020. The present study extended the analysis through July 2020 and examined firearm injuries from domestic violence separately from non-domestic violence.

“We know that access to firearms is a risk factor for intimate partner homicide. Last year, the increase in firearm purchasing combined with stay-at-home orders and multiple other stressors like job loss raised concern about increases in domestic violence,” Schleimer said.

As expected, the authors found states where firearm purchases went up the most showed the largest increases in firearm injuries from domestic violence. This was particularly true during April and May when social distancing was at its peak. However, they note results should be interpreted with caution since additional analyses showed that other, unmeasured variables might explain the association.   

States with highest average rate of firearm injuries from domestic violence per 100,000 population (March–July 2020)

1. Mississippi 0.23
2. Wyoming 0.17
3. West Virginia 0.16
4. Alabama 0.14
5. Louisiana 0.14

Firearm purchases and non-domestic violence

Surprisingly, the researchers did not find a similar correlation between excess firearm purchases and non-domestic violence at the state level. States with the largest increases in purchases from March through July 2020 did not experience the largest increases in non-domestic firearm violence.

“This was unexpected given prior studies. If we look at the country as a whole, we saw that purchasing and violence both went up on average. But when we looked state-by-state at the places in which firearm purchases increased the most, those weren’t the places where the violence increased the most,” Schleimer said.

To make these comparisons, the researchers tracked monthly firearm purchases per 100,000 population by state (using background checks as a proxy), along with monthly firearm injuries, fatal and nonfatal, per 100,000 people.

The data include the District of Columbia but not Alaska or Hawaii due to incomplete reporting. The study focuses on intentional, interpersonal firearm violence and does not include suicide or unintentional firearm injuries.

States and districts that had the highest rates of non-domestic firearm violence were the District of Columbia, Illinois, Louisiana, Missouri and Delaware.

States and districts with highest average rate of non-domestic firearm violence per 100,000 population (March–July 2020)

1. District of Columbia 10.2
2. Illinois 3.7
3. Louisiana 3.2
4. Missouri 2.6
5. Delaware 2.3

The results of the study suggest that pre-pandemic firearm access and other factors — major disruptions to routines, grief from the pandemic, economic strain and unemployment, and civic unrest — might have been important contributing factors to the pandemic-related increase firearm violence observed through July 2020.

“The increase in purchasing has continued unabated through the first half of 2021, and crime rates have increased as well. We, and others, will continue to examine the relationship between firearm availability and violence,” said Garen Wintemute, director of the UC Davis VPRP and professor of emergency medicine at UC Davis Health.

A joint research group from KAIST and Institut Pasteur Korea has identified repurposed drugs for COVID-19 treatment through virtual screening and cell-based assays. The research team suggested the strategy for virtual screening with greatly reduced false positives by incorporating pre-docking filtering based on shape similarity and post-docking filtering based on interaction similarity. This strategy will help develop therapeutic medications for COVID-19 and other antiviral diseases more rapidly. This study was reported at the Proceedings of the National Academy of Sciences of the United States of America (PNAS).

Researchers screened 6,218 drugs from a collection of FDA-approved drugs or those under clinical trial and identified 38 potential repurposed drugs for COVID-19 with this strategy. Among them, seven compounds inhibited SARS-CoV-2 replication in Vero cells. Three of these drugs, emodin, omipalisib, and tipifarnib, showed anti-SARS-CoV-2 activity in human lung cells, Calu-3.

Drug repurposing is a practical strategy for developing antiviral drugs in a short period of time, especially during a global pandemic. In many instances, drug repurposing starts with the virtual screening of approved drugs. However, the actual hit rate of virtual screening is low and most of the predicted drug candidates are false positives.

The research group developed effective filtering algorithms before and after the docking simulations to improve the hit rates. In the pre-docking filtering process, compounds with similar shapes to the known active compounds for each target protein were selected and used for docking simulations. In the post-docking filtering process, the chemicals identified through their docking simulations were evaluated considering the docking energy and the similarity of the protein-ligand interactions with the known active compounds.

The experimental results showed that the virtual screening strategy reached a high hit rate of 18.4%, leading to the identification of seven potential drugs out of the 38 drugs initially selected.

"We plan to conduct further preclinical trials for optimizing drug concentrations as one of the three candidates didn't resolve the toxicity issues in preclinical trials," said Woo Dae Jang, one of the researchers from KAIST.

"The most important part of this research is that we developed a platform technology that can rapidly identify novel compounds for COVID-19 treatment. If we use this technology, we will be able to quickly respond to new infectious diseases as well as variants of the coronavirus," said Distinguished Professor Sang Yup Lee.

Researchers at the National Cerebral and Cardiovascular Center in Japan show that excessive blood pressure reduction for acute intracerebral hemorrhage is risky in people with decreased kidney function

Suita, Japan -- Stroke and chronic kidney disease are both difficult to handle in their own rights, but having a stroke when your kidneys are already poor is more than just double the trouble. A new study led by Kazunori Toyoda at the National Cerebral and Cardiovascular Center (NCVC) in Japan shows that excessive blood pressure reduction for acute intracerebral hemorrhage can have dire consequences when kidney function is low. The study was published in the scientific journal Neurology®.

Intracerebral hemorrhage is a disease for which effective treatment is expected to be established. Abnormally high blood pressure is usually observed in the acute phase of intracerebral hemorrhage. Previous clinical studies have shown that intense blood pressure reduction in acute intracerebral hemorrhage patients can improve the clinical outcome. However, excessive blood pressure reduction can damage the kidneys, especially in people who already have chronic kidney disease. "Without a clear understanding of how kidney function affects the overall outcome when controlling blood pressure in these situations, doctors cannot make the best decisions for immediate stroke treatment," senior co-author Masatoshi Koga explains.

Kidney function is typically assessed using the estimated glomerular filtration rate (eGFR), which evaluates how well your kidneys are filtering out toxins from the blood. To determine if kidney function can affect the outcome after intracerebral hemorrhage, the researchers looked at data from an NIH-funded clinical trial, the Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-2), led by Professor Adnan I. Qureshi, a co-author of this article. In ATACH-2, patients within 4.5 hours of onset of intracerebral hemorrhage were randomly assigned to the intensive antihypertensive group (systolic blood pressure 110-139 mmHg) or the standard antihypertensive group (140-179 mmHg) and maintained in the target blood pressure range for 24 hours. The primary endpoint of the study was the rate of death or severe functional disability at 3 months.

In the current study, researchers divided patients into three categories based on their eGFR at the time of admission, which correspond to normal function, mild loss of function, and decreased kidney function.

The researchers found that the rate of death or disability after stroke was almost 50% in patients with decreased kidney function, compared with about 32% in patients with normal kidney function. They next looked at what happened when patients were treated with an intensive blood pressure-lowering regimen. They found that compared with the standard treatment, the effect of this intense treatment changed depending on the eGFR levels at admission. Among patients with decreased kidney function, the odds of death or disability were higher in patients treated with intensive blood pressure-lowering compared with those with standard blood pressure control. In contrast, the treatment effect (intensive vs. standard) was similar among the other two groups.

First author Mayumi Fukuda-Doi thinks that these findings have important implications. "Although intense lowering of blood pressure can reduce the risk of hematoma expansion and prevent brain damage after stroke, we found that it can harm those with eGFR values less than 60, who have decreased kidney function," she says. "Detailed mechanisms of the effects of excessively lowering of blood pressure in acute intracerebral hemorrhage patients, as well as the appropriate target blood pressure for those with kidney dysfunction, need to be studied. At present, renal function should be considered when deciding the optimal blood pressure range for each patient."