Body

New findings from a Michigan Medicine study reveal that antibody testing is predictive of prior COVID-19 infection, and rapid screening methods - even from finger pricks - are effective testing tools.

Researchers analyzed antibody tests conducted on more than 500 subjects in patient care settings. They found that people who had COVID, including those with mild symptoms, produced antibodies.

"For a long time, people were very worried that people with mild COVID did not make immune responses," says Charles Schuler, M.D., a clinical assistant professor of allergy and immunology at Michigan Medicine. "This should give people confidence that the tests that are available to them aren't just random number generators. They're actually giving them something useful."

The findings also indicate that rapid screens can predict infection with nearly the same precision as antibody tests conducted in a lab. Schuler, who led the research team, says the results could prove very useful for providers.

"I was actually surprised at how well some of these tests did because it's a very different experiment," Schuler says. "[If you have] a patient at a clinic that does not have a lab on site, we can find out if you had COVID before and we can do it now and we can do it at low cost."

The team examined lateral flow assays, which Schuler describes as modern litmus tests: A drop of blood or serum is placed on filter paper that changes color to indicate whether antibodies are present.

Researchers then compared three rapid screens taken by finger pricks or blood draws in point-of-care settings to serology tests assessed in a lab. They examined data from 512 patients, of which 104 had a history of COVID-19 and a positive PCR test.

Despite some false positives, two rapid tests agreed with positive lab results between 93 and 97 percent of the time. Both tests outperformed the third brand, which lost its FDA emergency use authorization during the trial.

"I think the FDA has done a nice job regulating bad tests out of the market," Schuler says. "These are still accurate in a point-of-care setting...[so], you've got a test that can be taken to different parts of the world and can be done without the need for a higher-complexity lab setting."

American vaccination is quickly ramping up - nearly 30 percent of the population received at least one dose as of March 30, according to the Centers for Disease Control and Prevention. But in places where immunization lags, Schuler says these point-of-care antibody tests could help determine who is prioritized.

"It's important to vaccinate everyone," he says. "But, if you can direct vaccines to people, in particular, who may be totally unprotected, something like this would be useful. I do think more data is needed to say that from a policy perspective."

The study population is limited, raising some questions about how the data can be generalized. Almost 90 percent of test subjects are health care workers, many providing direct care for COVID-19 patients.

However, Schuler's team will continue evaluating the subjects with a new focus. Some recent studies indicate antibodies may persist and offer protection for several months. Schuler hopes to make that answer more concrete.

"This is a down payment on, hopefully, a lot of great future data" he says. "While antibodies may or may not tell you how immunity happens, they might tell you about reinfection risk. That is the functional clinical significance that we need to know as soon as possible."

New "sweat stickers" may streamline the early diagnosis of cystic fibrosis by enabling scientists to easily gather and analyze sweat from the skin of infants and children. The stickers matched the performance of previous, more cumbersome devices when tested with 51 subjects, suggesting the stickers could address design obstacles that have held back the diagnosis and treatment of cystic fibrosis in pediatric patients. Diagnosing cystic fibrosis in infancy or childhood is critical to achieve good outcomes, as current treatments must be given early to extend lifespans and alter the course of the disease. Many current diagnostics work by detecting levels of chloride in sweat, which are elevated in cystic fibrosis patients. However, these tests must often be repeated and use unwieldy wrist-wrapped devices, making them impractical for infants with soft skin and low levels of sweat. To address this need, Tyler Ray and colleagues developed their sweat stickers, which are soft microfluidic devices with a multilayered design that can conform to the skin of both infants and adults. The stickers rapidly collect and store sweat from the skin, which scientists can then analyze using a smartphone application. The stickers collected sweat as effectively as a traditional method named MSCS in a pilot study with 18 healthy subjects and 33 patients ranging from 2 months to 51 years old. Unlike MSCS, the stickers gathered enough sweat to avoid any repeated tests and did not cause uncomfortable skin indentations in infants. The researchers call for larger studies to further establish their platform's accuracy and precision.

For many parents, the COVID-19 pandemic has made life's everyday juggling act--managing work, school, extracurricular, and household responsibilities--much, much harder. And according to a new study led by Penn sociologists, those extra burdens have fallen disproportionately on mothers.

The research, shared in the April issue of the journal Gender and Society, investigated how shifts in work and school that arose due to the pandemic triggered changes in the division of labor in families. Using data on two-parent households from a nationwide survey conducted in April 2020, the researchers found that gender disparities in unpaid labor were most apparent when a mother was the only parent working from home, or when neither parent was able to work remotely.

"It turns out that when the mother is working remotely and her partner isn't, she ends up taking on a ton more responsibilities," says Jerry Jacobs, a sociology professor in Penn's School of Arts & Sciences and one of the paper's authors. "When a father is working remotely and his partner isn't, somehow he doesn't take on as much extra work. This seems to be a deeply gendered issue."

As the pandemic has worn on, the toll on women has been hard to ignore. Each month, hundreds of thousands of women lost their jobs or dropped out of the workforce to meet new demands at home.

Yet remote work also seemed to open the possibility of greater equity between the genders in domestic responsibility, as two parents would be at home and accessible.

To tease out the effects of a shift to remote work on domestic labor during the pandemic, Jacobs, Penn doctoral student Allison Dunatchik, and colleagues turned to data from a New York Times survey, conducted by marketing research firm Morning Consult. Of 2,200 respondents, 478 were partnered parents, and 151 were single parents.

While the gender of each survey respondent's partner was unknown, the gender of the respondents themselves played a key role in how the pandemic affected their domestic responsibilities, which, with children largely at home, increased across the board.

Families where both partners worked remotely had the most egalitarian split of household and parenting duties, the researchers found. Both mothers and fathers reported similar increases in housework and childcare responsibilities, as well as in the pressure they felt about managing their children's schooling. Yet even this best-case-scenario was imbued with gender disparity, as pre-pandemic disparities endured. Mothers working remotely whose partners were also were more than twice as likely as fathers to report being the partner primarily responsible for housework and child care.

When only one parent worked remotely and the other worked out of the home, the gender disparity in domestic labor was far more evident. Mothers who worked from home essentially absorbed the extra labor, while fathers who worked remotely reported less uptake of the extra housework and child care than either mothers working from home alone or fathers who worked at home along with their partner.

"The disparity, how this affected remote dads versus remote moms, was just so stark," says Jacobs. "Even for a hard-boiled, data-driven sociologist like me, I was surprised."

"I had a similar reaction," Dunatchik says. "It's interesting when you compare the fathers working remotely alone to the fathers whose partners are also working from home. There's something interesting about the partner dynamics, it seems, that makes fathers more likely to pitch in in the presence of a partner."

When neither partner was able to work remotely, again mothers bore the brunt of the extra labor. In these couples, mothers were twice as likely as fathers to report increases in time spent on household labor and were seven times as likely to say they were the person responsible for the majority of children's home learning.

While the survey data had only 151 responses from single parents, most of which were women, the researchers found that, perhaps unsurprisingly, single mothers were spending more time on domestic labor, though they were less likely to have increased their time spent on housework during the pandemic than partnered mothers. "They were also less likely to report feeling significant pressure about their children's home learning compared to partnered mothers," says Dunatchik.

The survey was conducted about one month into the pandemic, so the researchers can only speculate about the lingering impact on gendered division of labor. Yet the researchers' findings provide a window into the pressures that may have driven some women's voluntary exit from the labor market. As more children return to in-person school, "some of that pressure will be reduced," Jacobs says. The longer-term impacts on women's seniority and loss of wages, however, could be significant and enduring, he says even if they do eventually return to full-time work.

One silver lining of the pandemic's "natural experiment" on remote work, the researchers say, may be increased work flexibility. With more opportunities for all parents to work from home, there may be more opportunities to move toward a more egalitarian division of responsibilities. "That's something that scholars have been pushing for a long time," Jacobs says.

An aggressive type of brain cancer, glioblastoma has no cure. Patients survive an average of 15 months after diagnosis, with fewer than 10% of patients surviving longer than five years. While researchers are investigating potential new therapies via ongoing clinical trials, a new study from Washington University in St. Louis suggests that a minor adjustment to the current standard treatment -- giving chemotherapy in the morning rather than the evening -- could add a few months to patients' survival.

The study appears online in the journal Neuro-Oncology Advances.

Average overall survival for all patients in the study was about 15 months after diagnosis. Those receiving the chemotherapy drug temozolomide in the morning had an average overall survival of about 17 months post diagnosis, compared with an average overall survival of about 13½ months for those taking the drug in the evening, a statistically significant difference of about 3½ months.

"We are working hard to develop better treatments for this deadly cancer, but even so, the best we can do right now is prolong survival and try to preserve quality of life for our patients," said co-senior author and neuro-oncologist Jian L. Campian, MD, PhD, an associate professor of medicine at the School of Medicine. "These results are exciting because they suggest we can extend survival simply by giving our standard chemotherapy in the morning."

Co-senior authors Joshua B. Rubin, MD, PhD, a professor of pediatrics and of neuroscience at the School of Medicine, and Erik D. Herzog, PhD, the Viktor Hamburger Distinguished Professor and a professor of biology in Arts & Sciences, developed a collaboration to study circadian rhythms and their effect on glioblastoma. Rubin and Herzog published studies in which they analyzed mouse models of glioblastoma and found improved effectiveness for temozolomide when given in the morning.

"In my lab, we were studying daily rhythms in astrocytes, a cell type found in the healthy brain," Herzog said. "We discovered some cellular events in healthy cells varied with time of day. Working with Dr. Rubin, we asked if glioblastoma cells also have daily rhythms. And if so, does this make them more sensitive to treatment at certain times? Very few clinical trials consider time of day even though they target a biological process that varies with time of day and with a drug that is rapidly cleared from the body. We will need clinical trials to verify this effect, but evidence so far suggests that the standard-of-care treatment for glioblastoma over the past 20 years could be improved simply by asking patients to take the approved drug in the morning."

In the current study, the researchers -- led by co-first authors Anna R. Damato, a graduate student in neuroscience in the Division of Biology & Biomedical Sciences, and Jingqin (Rosy) Luo, PhD, an associate professor of surgery in the Division of Public Health Sciences and co-director of Siteman Cancer Center Biostatistics Shared Resource -- also observed that among a subset of patients with what are called MGMT methylated tumors, the improved survival with morning chemotherapy was more pronounced. Patients with this tumor type tend to respond better to temozolomide in general. For the 56 patients with MGMT methylated tumors, average overall survival was about 25½ months for those taking the drug in the morning and about 19½ months for those taking it in the evening, a difference of about six months, which was statistically significant.

"The six-month difference was quite impressive," Campian said. "Temozolomide was approved to treat glioblastoma in 2005 based on a 10-week improvement in survival. So, any improvement in survival beyond two months is quite meaningful."

In this retrospective study, the researchers analyzed data from 166 patients with glioblastoma who were treated at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine between January 2010 and December 2018. All patients received the standard of care for glioblastoma. They underwent surgery to remove as much of each tumor as possible and then received radiation therapy along with the chemotherapy drug temozolomide. After the radiation and temozolomide regimen was complete, patients continued taking a maintenance dose of temozolomide -- taken as an oral capsule -- either in the morning or evening, depending on the preference of their oncologists.

"Until now, we have never considered that the timing of temozolomide might be important, so it's up to the treating physician to advise the patient on when to take it," said Campian, who treats patients at the Brain Tumor Center at Siteman. "Many oncologists give it in the evening because patients tend to report fewer side effects then. We saw that in our study as well. But it could be that the increased side effects -- which we can manage with other therapies -- are a sign that the drug is working more effectively."

Added Damato: "There have been screens of different drugs given to cells at different times of day, and huge percentages of these drugs are shown to have time-of-day dependent effects on cell survival. For example, how the drug is absorbed might change throughout the day. So, side effects could change throughout the day."

Campian cautioned that this was a relatively small retrospective analysis. She and her colleagues are conducting a clinical trial in which newly diagnosed glioblastoma patients are randomly assigned to receive temozolomide in either the morning or evening. Such trials will be needed to establish whether treatment timing can truly improve survival for glioblastoma patients.

"There have been no new drugs approved for glioblastoma in over a decade," Luo said. "That makes it necessary to think about other possible changes that make a drug more efficacious. Chronotherapy -- or the timed delivery of drugs, based on circadian rhythms -- is becoming a popular topic. It's practical and realizable to implement chronotherapy to optimize existing drugs and treatments."

Houston Methodist has been a leader in successfully treating high-risk patients with monoclonal antibodies (mAB) for mild to moderate Covid-19 infection. Among the nation's largest providers of mAB therapy, Houston Methodist has infused nearly 4,000 patients since the FDA's Emergency Use Authorization (EUA) was issued. The hospital system was able to quickly ramp up its program once the EUA was granted by leveraging a number of resources through interdisciplinary collaboration.

As more hospitals begin to ramp up for treating Covid-19 with mAB therapy, Houston Methodist's example serves as a valuable model for other medical systems to establish or expand mAB treatment programs and improve patient access to this critical therapy. A commentary outlining the challenges, resources used and benchmarks of success published online March 29 in the New England Journal of Medicine Catalyst.

Houston Methodist drew upon its experience with clinical trials on other Covid-19 therapies and forged early partnerships with industry through the Houston Methodist Research Institute to conduct mAB clinical trials beginning early on in the pandemic. Doing so helped the hospital system overcome a number of obstacles to rapidly establish and scale up treatment clinics to bring mAB therapy to thousands of patients. Challenges included designing clinics using existing resources to separate Covid-19 positive patients from other hospitalized patients, establishing a referral stream that could treat large patient volumes and maintaining a sufficient drug supply to treat all patients.

Highlights included establishing six clinics in less than six weeks across the greater Houston area throughout Houston Methodist's system of hospitals; having an average of 1.2 days from referral to treatment; infusing more than 2,500 patients; and avoiding nearly 250 Covid-19-related hospitalizations. Some of these numbers have increased since the initial study period published in NEJM. Another mark of success, some patients have traveled as many as eight hours to receive mAB therapy at Houston Methodist. This also suggests a need for other healthcare systems to create or expand mAB infusion clinics to improve availability for those unable to travel.

CLEVELAND, Ohio (March 31, 2021)--Menopause typically signals the end of a woman's ability to become pregnant. However, in a small new study, a novel approach of administering platelet-rich plasma and gonadotropins near the ovarian follicles is showing promise in restoring ovarian function. Study results are published online today in Menopause, the journal of The North American Menopause Society (NAMS).

As more women look to build their careers before pursuing motherhood, the average age of conceiving a child continues to be pushed back. For some of these women, however, their hope of becoming pregnant is cut short by the onset of early menopause, which is described as the cessation of ovarian function at or before the age of 45 years. It is estimated that roughly 12.2% of women experience early menopause. For these women, the only chance of becoming pregnant is with donor eggs.

Multiple treatment options have previously been investigated, including standard, controlled ovarian stimulation. Platelet-rich plasma has been used in women with primary ovarian insufficiency, but few pregnancies and live births resulted. With the failure of these somewhat traditional treatments, more novel approaches, such as methods for inducing the growth of ovarian follicles, are being pursued.

In this new, small-scale pilot study, platelet-rich plasma and gonadotropins were injected into the ovaries of study participants, with some fairly amazing results. After treatment, 11 of the 12 study participants resumed menstruation, and one achieved clinical pregnancy, defined as a pregnancy that is confirmed by ultrasound as well as a fetal heartbeat.

Although more research and larger studies are needed, these early results regarding the successful resumption of ovarian function offer hope to women in early menopause who may be able to pursue pregnancy through in vitro fertilization using their own eggs.

Results are published in the article "Resumed ovarian function and pregnancy in early menopausal women by whole dimension subcortical ovarian administration of platelet-rich plasma and gonadotropins."

"This pilot study investigating the use of platelet-rich plasma and gonadotropins injected into the ovaries of women with early menopause highlights the promise of regenerative medicine in restoring or prolonging fertility. Additional studies conducted prospectively and involving large numbers of women are needed to determine whether this is truly a viable option for women with early menopause hoping to achieve pregnancy using their own eggs," says Dr. Stephanie Faubion, NAMS medical director.

WASHINGTON, DC - March 31, 2021 -- Nearly 20% of Americans, or more than 46 million adults, say they did not seek treatment for a health problem in the last year due to cost, and an equal number say that if they needed some form of healthcare today they would not be able to afford it, according to a new West Health-Gallup survey. The findings come as Americans struggle through a year-plus long pandemic that has claimed over 550,000 lives and put millions of people out of work.

Americans who found themselves unemployed were about twice as likely (38%) to avoid medical care due to cost in the last year. And, while Black, Hispanic and White Americans skipped treatments in roughly equal numbers last year, more people of color are worried about what the future may hold. Nearly one-third (29%) of Black adults - nearly double the number of White adults - and more than one-fifth of Hispanic adults (21%), say if they needed healthcare today, they could not afford it.

"The COVID-19 pandemic has upended life over the last year, and as we begin to emerge from the worst public health crisis in 100 years, we are left with another crisis that has never gone away - the high cost of healthcare," said Tim Lash, chief strategy officer for West Health, a family of nonprofit and nonpartisan organizations dedicated to lowering healthcare costs to enable successful aging. "Millions of Americans simply can't afford healthcare and policymakers simply can't continue to ignore this painful truth."

In the last year, tens of millions of Americans say they were forced to cut back on basic necessities like food (12%) and utilities (9%) to pay for healthcare, while 35% say they reduced spending on recreational activities and 26% reduced spending on clothing. Nearly 30% found paying for general healthcare a significant financial burden behind housing (51%), taxes (48%) and food (41%). Costs for prescription drugs are a significant financial burden for more than 1 in 5 adults (22%). The survey also found that more than half (52%) of all Americans say they are either "worried" or "very worried" that a health event will wipe out their savings.

This may explain why the American public overwhelmingly favors reforms including setting caps in Medicare on out-of-pocket costs for prescription drugs (88%) and general healthcare services (85%). Majorities of Americans also support lowering the age of Medicare eligibility to 60 (65%), making Medicare available to everyone (60%) and strengthening the Affordable Care Act (59%), though Democrats are much more likely to support these latter three measures than are Republicans. Slight majorities of Independents support the measures.

"Our surveys consistently show that the high cost of healthcare is a significant worry for tens of millions of Americans and that these concerns have persisted throughout the course of the COVID era," said Dan Witters, Gallup senior researcher. "As the pandemic recedes and normalcy slowly returns to everyday life, anxiety over affording quality care appears likely to again become a primary issue for elected officials to address."

Cancer patients generally have a higher thrombotic risk than the population at large. This risk is influenced on the one hand by patient-specific factors and the cancer itself and, on the other, by the cancer treatment, that is to say surgery, radiotherapy, or specific chemotherapeutics, which can increase the risk.

In the last few years, immune checkpoint inhibitors have increasingly been used to treat many different types of cancer. By activating the immune system against the tumour, these drugs improve the prognosis for patients with malignant melanoma, lung cancer, renal cell carcinoma and other types of cancer. "Patients who are treated with immune checkpoint inhibitors have often had previous cancer treatment and, in most cases, have advanced cancers. We might therefore expect a significant risk of thromboembolism but, so far, the large-scale treatment studies conducted for immune checkpoint inhibitors have not reported on it," says Principal Investigator Cihan Ay, who, like Florian Moik, is also associated with the Comprehensive Cancer Center (CCC) of MedUni Vienna and Vienna General Hospital.

In order to close these gaps in knowledge, a cohort study was launched to gather data on venous and arterial thromboembolism in patients treated with immune checkpoint inhibitors at MedUni Vienna/Vienna General Hospital between 2015 and 2018. A total of 672 patients, who had received such treatment for an average of 8.5 months, were included. The result: "The cumulative incidence of venous thromboembolism was 12.9% and of arterial thromboses 1.8%. This risk appears to be independent of the underlying type of cancer and the immune checkpoint inhibitor used, since similar rates of thrombosis were observed in these subgroups," explains Florian Moik. The occurrence of venous thromboembolism was associated with a poorer prognosis and a shorter time before tumour progression. Moreover, they frequently resulted in delays to or even discontinuation of treatment and were associated with a significant risk of recurrent thromboses and haemorrhages during anticoagulation treatment.

"The results underscore the negative impact of venous and arterial thromboembolism on the clinical course of cancer patients," says study author Moik in summary. "This study fails to determine whether the high risk of thromboembolism that has been observed has a causal link with immune-checkpoint-inhibitor therapy or merely reflects the underlying basic risk in this patient group." Irrespective of this, he believes it is important to build awareness of these complications, particularly in the light of the high efficacy of this new cancer treatment. "This paper therefore serves as a basis for future studies with a view to identifying patients who could benefit from thrombosis prophylaxis, especially to prevent venous thromboembolism."

HERSHEY, Pa. -- Stress, increased free time and feelings of boredom may have contributed to an increase in the number of cigarettes smoked per day during the early months of the COVID-19 pandemic by nearly a third of surveyed Pennsylvania smokers. Penn State College of Medicine researchers said understanding risk factors and developing new strategies for smoking cessation and harm reduction may help public health officials address concerning trends in tobacco use that may have developed as a result of the pandemic.

Jessica Yingst, assistant professor of public health sciences and Penn State Cancer Institute researcher, said smokers who increased the number of cigarettes they smoked per day could be at greater risk of dependence and have a more difficult time quitting.

Researchers asked 291 smokers about their tobacco use patterns before and during the early months of the pandemic including how frequently they used tobacco products, reasons why their use patterns changed and whether they attempted to quit. Nearly a third of smokers reporting increased use due to stress, increased free time and boredom. One participant stated, "Working at home allows me to smoke at will rather than being in a smoke-free environment for 8 hours per day." In contrast, 10% of participants decreased their tobacco use and attributed that to schedule changes, being around non-smokers such as children, and health reasons.

Nearly a quarter of participants reported attempting to quit smoking during the pandemic. A third of those who attempted to quit conveyed that they did so to reduce their risk of poor outcomes should they become infected with COVID-19. One participant stated, "I quit as soon as I came down with a fever and cough. Clearly, I am aware of how detrimental smoking is to my health; however, I did not consider how it could make me more vulnerable to COVID-19 and its effects. I was terrified and quit immediately." Ultimately, seven people were successful in quitting all tobacco use.

The research team also asked the participants about their perceptions of health risks during the pandemic. More than two-thirds of participants believed their risk of contracting COVID-19 was the same as non-tobacco users. However, more than half of those surveyed thought they were at higher risk to suffer serious complications from COVID-19. The results were published in the International Journal of Environmental Research and Public Health.

"Knowing the reasons for increased tobacco use and the motivations of those who successfully quit smoking can help us identify how to better address cessation efforts during the pandemic," Yingst said. "New methods like telemedicine and increasing public health messaging could encourage people to stop smoking in the absence of public support groups or other in-person interventions."

March 30, 2021 - As cancer survival rates improve, more people are living with the aftereffects of cancer treatment. For some patients, these issues include chronic radiation-induced skin injury - which can lead to potentially severe cosmetic and functional problems.

Recent studies suggest a promising new approach in these cases, using fat grafting procedures to unleash the healing and regenerative power of the body's natural adipose stem cells (ASCs). "Preliminary evidence suggests that fat grafting can make skin feel and look healthier, restore lost soft tissue volume, and help alleviate pain and fibrosis in patients with radiation-induced skin injury after cancer treatment," says J. Peter Rubin, MD, MBA, FACS, American Society of Plastic Surgeons (ASPS) President-Elect and Chair of the Department of Plastic Surgery at University of Pittsburgh Medical Center. He is one of the authors of a new review of the clinical evidence on fat grafting for radiation-induced skin and soft tissue injury.

"But while promising, available research has some key weaknesses that make it difficult for us to determine the true benefits of fat grafting right now," Dr. Rubin adds. The review appears in the April issue of Plastic and Reconstructive Surgery®, the official medical journal of the ASPS.

More than half of patients diagnosed with cancer receive radiation therapy. Because skin cells turn over rapidly, they are exquisitely sensitive to the damaging effects of radiation. In the first few months after treatment, many patients develop acute radiation injury with skin inflammation, peeling, swelling, pain and itching. In most cases, symptoms resolve over time. However, if inflammation continues, radiation-induced skin injury can become a chronic problem leading to tight, stiff skin (fibrosis) with a risk of poor wound healing, ulcers, and tissue loss.

Fat grafting procedures - transferring the patient's own fat cells from one part of the body to another - have become widely used in many cosmetic and reconstructive plastic surgery procedures. In their review, Dr. Rubin and colleagues round up promising research on fat grafting for patients with radiation-induced skin injury.

In studies of breast cancer patients, fat grafting procedures have reduced pain and other symptoms of radiation-induced skin injury - backed up by more-normal cellular appearance of skin cells under the microscope. In other studies, fat grafting has led to reduced risks and better outcomes of breast reconstruction after mastectomy.

For patients with radiation-induced skin injury after treatment for head and neck cancer, fat grafting has led to improvements in voice, breathing, swallowing, and movement. Good outcomes have also been reported in patients with radiation-induced skin injury in the area around the eye or in the limbs.

"The good news is fat grafting has the potential to really help patients with discomfort and disability caused by radiation-induced skin damage," according to Dr. Rubin. While research is ongoing, the benefits of fat grafting seem to result from the wide-ranging effects of ASCs - including anti-scarring, antioxidant, immune-modulating, regenerative, and other actions.

"However," he adds, "the available evidence has a lot of shortcomings, including small sample sizes, lower-quality research designs, and a lack of comparison groups." Variations in fat cell collection and processing, as well as the timing and "dose" of fat grafting, make it difficult to compare results between studies. There are also unanswered questions regarding potential risks related to ASC injection and concerns that fat grafting might affect cancer follow-up.

The reviewers outline some steps for further research to clarify the benefits of fat grafting for radiation-induced skin and soft issue injury, including approaches to clinical assessment and imaging studies, testing of skin biomechanics and circulation, and cellular-level analyses. For all of these outcomes, standardized measures are needed to achieve more comparable results between studies.

"We hope our review will inform efforts to establish the benefits of specific types of fat grafting procedures in specific groups of patients," says Dr. Rubin. "To do that, we'll need studies including larger numbers of patients, adequate control groups, and consistent use of objective outcome measures."

WASHINGTON, March 30, 2021 -- Emerging technologies can screen for cervical cancer better than Pap smears and, if widely used, could save lives both in developing nations and parts of countries, like the United States, where access to health care may be limited.

In Biophysics Reviews, by AIP Publishing, scientists at Massachusetts General Hospital write advances in nanotechnology and computer learning are among the technologies helping develop HPV screening that take the guesswork out of the precancer tests. That could mean better screening in places that lack highly trained doctors and advanced laboratories.

Cervical cancer is the world's fourth-most common cancer, with more than 500,000 cases diagnosed every year. Almost all cases of cervical cancer are caused by HPV, or human papillomavirus. Detecting precancer changes in the body gives doctors a chance to cure what could otherwise become a deadly cancer.

Pap smears, which were introduced in the 1940s, are subjective and not always reliable. The tests, which can detect about 80% of developing cervical cancer if given regularly, require high-quality laboratories, properly trained clinical doctors, and repeated screenings. These test conditions are not widely available in many countries or even in low-income and remote parts of wealthier nations.

"The Pap smear has done wonders in terms of reducing mortality from a cancer that is very treatable when caught early and almost invariably fatal when it is caught late," said author Cesar Castro, an oncologist at Massachusetts General Hospital and associate professor at Harvard Medical School. "And it is not even a great test. Part of its imperfection is that there is subjectivity to it. The trained eye is the limiting step in the process. The untrained eye, or relatively untrained eye, can miss cancers."

The subjectivity of the test has led to a much higher death rate from cervical cancer in lower-income countries. The authors highlight a list of existing and emerging technologies that can be used to close the testing gap in those areas. They range from existing DNA testing and other Pap smear alternatives to next-generation technologies that use recent advances in nanotechnology and artificial intelligence.

One technique involves screening with tiny beads made of biological material that form a diamond shape when they contact HPV. Those shapes can be detected with powerful microscopes. When those microscopes are not available, a mobile phone app, built through machine learning, can be used to read them.

"Similar to COVID-19 testing, we have great technology in places like the United States that does not work well enough in other countries," said author Hyungsoon Im, a biomedical engineer at Massachusetts General Hospital and assistant professor at Harvard Medical School. "This is why there is great motivation to find next-generation, affordable technology to address this problem."

ARLINGTON, Va., March 30, 2021 — Doctors who oversee cancer clinics say that new patients are arriving for treatment with more advanced disease than before the COVID-19 pandemic, according to a new survey from the American Society for Radiation Oncology (ASTRO). The national survey of radiation therapy practice leaders fielded this winter also indicates that treatment postponements and deferrals that were common a year ago have largely subsided and that clinics continue to use a variety of enhanced safety measures to protect their patients and staff.

"One year into the COVID-19 pandemic, we already see the consequences of pandemic-driven drops in cancer screening and diagnostics," said Thomas J. Eichler, MD, FASTRO, Chair of the ASTRO Board of Directors.

Two-thirds of the radiation oncologists (66%) said new patients are presenting with more advanced-stage cancers. Nearly three-fourths (73%) said physicians in their practice are noticing that patients are not receiving cancer screenings, and many also said existing patients experienced an interruption in their radiation treatment due to the pandemic (66%).

"Because the pandemic and cancer cause disproportionately more harm for Black and other medically underserved populations, these rates may be even higher for some vulnerable communities," added Dr. Eichler.

Enhanced safety protocols remain widespread at radiation therapy clinics. Masking for patients and staff (99%), social distancing in the clinic (100%) and screening patients and staff for COVID-19 exposure (95%) are nearly universal. Increased sterilization (93%), face shields for staff during procedures (80%) and no-visitor policies (73%) are also common.

"Safety is at the core of radiation oncology, and clinics were ready to adapt quickly and ramp up protective measures that keep their staff and patients safe from COVID-19 exposure," said Dr. Eichler.

The survey also found that clinics have largely stopped deferring or postponing radiation treatments. Only 15% reported postponing treatment in January/February 2021, compared to 92% in April 2020. Similarly, 12% reported deferring any new patient visits in 2021, compared to 75% in the early weeks of the pandemic.

Four in 10 practices still reported difficulty accessing personal protective equipment, medical-grade hand sanitizer or other critical supplies in the initial months of 2021. More alarmingly, many physicians said that COVID-19 vaccination efforts at their practice were limited by access to the vaccine (53%), and by hesitation to receive the vaccine among staff (59%) and patients (52%). The high rates of hesitancy echo findings that more than half of frontline health care workers in the U.S. were unvaccinated as of early March 2021.

ASTRO recently joined a coalition led by the American Cancer Society and National Comprehensive Cancer Network to encourage the American public to resume cancer screening and treatment, emphasizing that cancer won't wait until the pandemic ends. ASTRO also updated its COVID-19 clinical guidance to include support for COVID-19 vaccination for people receiving radiation therapy, as long as the individual does not have increased risk of a reaction to the vaccine. Patients are encouraged to consult with their radiation oncologist regarding timing and location of the injection.

Additional Survey Findings

The pandemic is not affecting clinics equally. Radiation oncologists at community-based private practices were more likely to report seeing advanced-stage cancers among their patients, compared to those at university-affiliated clinics. PPE shortages and pandemic-related treatment interruptions were also more common at private practices. Differences emerged regarding the COVID-19 vaccine, as well. Both vaccine access and vaccine hesitation were more problematic barriers for clinics located outside of major metropolitan areas (i.e., population

Telemedicine remains popular. More than 8 in 10 clinics (85%) offer telemedicine options for follow-up surveillance visits, and more than half (54%) do so for new patient consultations. Fewer clinics (15%) use telemedicine for clinician assessments of patients who are undergoing radiation treatments.

Radiation therapy clinics continue to face financial and operational challenges created by the pandemic. Patient volume dropped at 73% of clinics due to the COVID-19 pandemic, and visits were down 21%, on average. Most practices (72%) reduced staff at some point due to the COVID-19 pandemic.

Clinics have stayed open, however. One hundred percent of the physicians surveyed said their radiation therapy networks remained open during multiple spikes of the pandemic. Just 7% closed any satellite locations.

Survey Methodology

An online survey was sent by email to 509 radiation oncologists identified in ASTRO’s member database as medical directors of U.S. based radiation oncology practices, and 117 physicians completed the survey online January 15 through February 7, 2021 (23% response rate). For more information about respondent demographics, view the survey report.

Researchers at the Johns Hopkins Kimmel Cancer Center used machine learning techniques to detect mutational signatures in cancer patients. Their algorithm outperformed the current standard of analysis and revealed new mutational signatures associated with obesity, which is believed by cancer prevention experts to be becoming the most significant lifestyle factor contributing to cancer in the U.S. and most of the Western world.

The study was published in the Jan. 25 issue of the journal eLife.

"Mutational signatures are important in current cancer research as they enable you to see the signs left by underlying factors, such as aging, smoking, alcohol use, UV exposure, and BRCA inherited mutations that contribute to the development of a cancer," says study leader, Cristian Tomasetti, Ph.D., associate professor of oncology at the Johns Hopkins Kimmel Cancer Center, with a joint appointment in Biostatistics at the Johns Hopkins Bloomberg School of Public Health.

The new technique uses an application of artificial intelligence called machine learning, via a computer algorithm that accesses and analyzes data to uncover what they call SuperSigs, which are mutational signatures that reveal the genetic effects of the underlying contributors to cancer. Their algorithm is classified as "supervised" because it is an analysis that includes known exposures during the training of the algorithm for the genetic analysis of a cancer. The most widely used mutational signatures used for assessing genomic data are classified as "unsupervised" because they do not take known exposures into consideration. Instead, it notes patterns and then goes back to correlate them with exposures. The new method also allows for a mix of supervised and unsupervised approaches, controlling or blocking out the effect of known exposures to carcinogens to explore the possible effect of potential unknown factors.

The researchers found that the new supervised technique outperformed the unsupervised methodology in terms of prediction accuracy. The supervised methodology had a median area under the curve (AUC) of 0.73 for aging and 0.90 for all other factors, while the unsupervised methodology had a median AUC of 0.57 for aging and 0.77 for all other factors.

"A 0.5 or below AUC means the method is not better than pure chance. The highest value you can get is 1," says first author Bahman Afsari, Ph.D., an instructor at the Johns Hopkins Kimmel Cancer until a few months before publication.

They also revealed what they believe are the first mutational signatures associated with cancers of obese patients, providing evidence for a mutational mechanism related to obesity and the origination of cancers.

"Obesity is arguably the most important lifestyle factor contributing to cancer, but its mechanism for causing cancer has been unknown," says Tomasetti. "As cancers of obese patients often do not appear to have an increased number of mutations, it was thought that the mechanism through which obesity increases cancer risk was not via mutations. Our results show that it is, at least in part, mutational."

Their method also showed that an etiological, or underlying, factor does not always cause the same mutational effect on all tissues, a discovery that was contrary to assumptions of the unsupervised methodology.

"Aging yields different mutational signatures in different tissues, and so do smoking and several other environmental exposures," says co-first author Albert Kuo, Ph.D. candidate at the Johns Hopkins Bloomberg School of Public Health. "Also, in lungs, the signature for aging and the signature for smoking are very different, but in other tissues, the signature of smoking is relatively similar to the signature for aging, suggesting inflammation as the main mechanism."

Additionally, the research provided validation for the key role of random mutations--normal mistakes occurring within the DNA of cells during replication--in the development of a cancer.

"Every time a cell divides, it has to duplicate its DNA. As the duplication and repair machinery copies the billions of letters--the molecules that make up our DNA--mistakes are made. It is estimated that there are between three to six DNA mutations occurring every time a cell divides," explains Tomasetti. "A major source of the mutations that cause cancer appears to be these endogenous processes that have nothing to do with genetic defective genes or harmful exposures."

Through the algorithm, Tomasetti and team determined that 69% of the mutations found in cancer patients across all tumor types can be attributed to randomly occurring mutations, pointing to a need for a greater focus of effort and resources on early detection, he says.

"If we can't avoid cancer from occurring, then the next best thing is to find it before it is too late. If we can find a cancer at an early stage, then typically, you can save the life of the patient," he says.

DALLAS - March 30, 2021 - UT Southwestern researchers have identified factors that put patients with childhood-onset lupus at elevated risk for poor outcomes, such as end-stage renal disease or death, as they transition from pediatric to adult health care. The findings, published online in Seminars in Arthritis and Rheumatism, emphasize the precarious nature of this period and shine a spotlight on areas prime for intervention to help protect these vulnerable patients.

Patients with chronic diseases that used to be fatal early in life now often survive to live long lives. However, says study senior author Bonnie Bermas, M.D., professor of internal medicine at UTSW, while pediatric patients often have significant support in managing their conditions as children, they are expected to take much more responsibility for their health care as they transition to adult care.

Studies have shown that patients with chronic diseases such as HIV and sickle cell disease tend to have poor outcomes during this time. As an adult rheumatologist who cares for young adult patients with childhood-onset lupus erythematosus, an autoimmune disease, Bermas says she has witnessed a similar phenomenon. However, it's unclear what factors put young lupus patients who transition to adult care at higher risk.

To explore this question, Nicole Bitencourt - a former UTSW pediatric and adult rheumatology fellow who is now on the faculty of the University of California Los Angeles Medical Center - along with Bermas and her UTSW colleagues used medical records to identify childhood-onset lupus patients who transitioned to adult care between 2010 and 2019. These 190 patients were seen at two different rheumatology clinics: One is a safety-net hospital that mainly treats patients with public insurance; the other is a university hospital that primarily sees patients with private insurance.

The researchers followed patients for an average of nearly 3.5 years and looked at three major outcomes: time to the first hospitalization following a patient's final pediatric rheumatology visit; time to end-stage renal disease, a condition in which severe kidney failure necessitates dialysis; and death.

Of the 190 patients, 11 percent developed end-stage renal disease and 5 percent died during the follow-up period. Out of 114 patients with hospitalization data, 53 percent were hospitalized as young adults.

The research team found several factors linked with these poor outcomes. End-stage renal disease and death were associated with having public health insurance, a history of Child Protective Services involvement, and an unscheduled hospitalization during the final year of pediatric care. A shorter time to hospitalization in adult care was linked with a pediatric outpatient opioid prescription and Black race or Hispanic ethnicity.

Bermas, the Dr. Morris Ziff Distinguished Professor in Rheumatology, notes that these findings could help health care providers better target childhood-onset lupus patients who might be at higher risk of poor outcomes during their transition to make sure they have the support and resources needed to stay healthy after they become adults.

"Transitioning to young adulthood has its own challenges, but these patients are struggling with a chronic disease on top of that. We're asking an awful lot of these patients to navigate the medical system, often with little support," says Bermas. "By identifying those patients who may need more help, we can improve outcomes and even potentially save lives."

Researchers at Cincinnati Children's Hospital Medical Center have developed a new framework for different factors influencing how a child's brain is "wired" to learn to read before kindergarten.

This may help pediatric providers identify risks when the brain is most responsive to experiences and interventions. This "eco-bio-developmental" model of emergent literacy, described in the journal JAMA Pediatrics, reinforces the potential of early screening, prevention, and intervention during pediatric clinic visits in early childhood.

This kind of model is advocated by the American Academy of Pediatrics to help better understand and improve important social determinants of health.

"Emergent literacy is a developmental process beginning in infancy, when the brain is rapidly developing. It involves skills, knowledge, and attitudes that are precursors to reading and writing," said John Hutton, MD, director of the Reading & Literacy Discovery Center at Cincinnati Children's. "Reading difficulties stem from deficits in any of these domains and take root early with far too many children beginning kindergarten unprepared to learn to read and at-risk of falling farther behind. Our research shows this is especially true for children from minority and impoverished backgrounds."

The model is separated into three categories: 1) ecological, 2) biological and 3) developmental. Ecological includes experiences in a child's home environment, such as reading, talking, teaching, and creative play. Biological includes genetics such as family history of dyslexia and medical conditions such as prematurity. Developmental includes cognitive, social-emotional, and brain health and abilities.

"Importantly, our model anchors these factors to neurobiology, which reflects how a functional 'reading network' develops in a child's brain," Hutton said. "Through neuroimaging, especially MRI, our research has found that more stimulating reading activities in the home environment prior to kindergarten are related to better developed brain structure and also function supporting literacy."

Cincinnati Children's has several programs in place for parents help their child, both in and out of the hospital. A new program is called "NICU Bookworms," through which families receive free books and encouragement to read to their baby during their stay in intensive care, which can be days or months long. They also receive empowering guidance on the benefits of "shared" book reading by trained NICU teams. This is an important resource, as families are often anxious about what they can do to help their child.

The program was part of a 2018-2019 study by neonatologists from Cincinnati Children's caring for babies in the NICU at the medical center and other local hospitals. The results, published recently in the Journal of Pediatrics, showed high-risk parents were five times more likely to read to their baby at home due to the intervention that took place at the hospital and that reading reduced the anxiety they felt during their child's stay.

A new book titled Baby Bookworm, written by Dr. Hutton and neonatologist Dr. Viral Jain, MD, to reinforce the NICU Bookworms program, was recently published. It gives parents in the NICU at Cincinnati Children's and other hospitals a way to help them bond with their babies.

Other early reading programs featured in the eco-bio-developmental model include: Reach Out and Read, through which children receive a new book and guidance about reading at home during well-visits from newborn through age 5; and Dolly Parton's Imagination Library, which mails new books to the child's home once a month from birth through age 5. Each of these are well-established at Cincinnati Children's, in Ohio and nationally.

Hutton also recently developed a new screening tool featured in the model called The Reading House, described in a recent study published in Pediatrics, which directly engages preschool-age children during clinic visits so pediatricians can assess their early literacy skills. The book has the potential to identify reading difficulties as early as age 3, target interventions to skills, and empower families to help their child at home.

"Rather than a passive approach, early literacy screening and interventions that are administered by pediatric practitioners through this new model can help identify potential reading difficulties, address risk factors during a period when neural plasticity is high, and improve outcomes," Hutton said.