Body

WASHINGTON--Only 3% of patients at high risk for primary aldosteronism (PA), a common disorder that causes high blood pressure and can lead to heart and kidney complications, are screened for the condition, according to a study that will be presented virtually at ENDO 2021, the Endocrine Society's annual meeting.

"The results of our study indicate that initiatives to encourage PA screening are crucial for preventing cardiovascular and kidney disease in many patients with hypertension," said lead researcher Seda Grigoryan, M.D., of Michigan State University in Lansing, Mich.

PA is the most common form of secondary hypertension--high blood pressure caused by another disease. Nearly half of adults in the United States have high blood pressure. PA occurs when the adrenal glands produce too much aldosterone, the hormone responsible for balancing potassium and sodium in the body. Overproduction of aldosterone causes the body to retain more sodium and lose potassium. This leads to elevated blood pressure, increasing the risk of heart and kidney disease.

Patients with PA have a higher risk of developing cardiovascular and kidney complications compared with patients with primary hypertension (high blood pressure without an apparent cause) with similar blood pressure.

The researchers reviewed data for adult patients with hypertension seen in outpatient clinics between 2010 and 2019 who were known to be at risk for PA. Of 11,627 patients, only 3% were ever screened for PA. Risk factors included hypertension resistant to treatment, hypertension below age 40, hypertension and obstructive sleep apnea, hypertension and potassium deficiency, and hypertension and a mass in the adrenal gland.

Patients who were screened generally were younger, and Black patients were more likely to be screened than those of other races. Grigoryan found the diagnosis of PA was suspected more often after complications--such as strokes and kidney disease--had already developed. Of the patients at risk for PA, screening was done most often in those with adrenal nodules (35%) and least often in those with sleep apnea (2%).

WASHINGTON--A lifestyle intervention targeting women with obesity and infertility is more effective in increasing the pregnancy rate compared with fertility treatments, according to a study presented virtually at ENDO 2021, the Endocrine Society's annual meeting.

The lifestyle intervention, called the Fit-For-Fertility (FFF) program, is a cost-effective alternative to the usual standard of care for women with obesity seeking fertility treatments, according to lead researcher Matea Belan, Ph.D., of the University of Sherbrooke and the Research Center of the Centre Hospitalier Universitaire de Sherbrooke (RC-CHUS) in Quebec, Canada. "Our study shows that the FFF program can significantly improve the pregnancy rate, especially the spontaneous pregnancy rate when no fertility treatments are required, as well as the live-birth rate," she said.

Obesity is a known risk factor for infertility in women of childbearing age. Lifestyle changes and a moderate weight loss of 5%-10% of a woman's initial weight have been shown to improve the odds of a pregnancy in women with obesity and infertility, Belan noted.

"Lifestyle changes are recommended as the first-line treatment for these women," said study author Jean-Patrice Baillargeon, M.D., M.Sc., professor of the University of Sherbrooke and clinician investigator of the RC-CHUS. The new study tested Fit-For-Fertility, a multidisciplinary lifestyle intervention that includes a nutritionist and a kinesiologist, or human movement specialist.

The researchers recruited 130 women receiving treatment at a fertility clinic, and randomly divided them into two groups. The first group had access to the Fit-For-Fertility program alone for the first six months of their participation, and in combination with fertility treatments if no pregnancy occurred after six months.

The program included individual sessions with a nutritionist and a kinesiologist every six weeks. Women in the FFF group were also asked to follow at least once each one of the 12 group sessions, which included a 45-minute workshop on topics regarding nutrition, lifestyle changes and lifestyle habits, followed by a 45-minute session of initiation to different types of physical activity, including walking, circuit training, step workout and others. In the second group, the control group, women had access to the fertility treatments from the outset but did not take part in the FFF program.

Data was collected for 18 months, or until the end of a pregnancy for women who became pregnant during those 18 months of participation.

Of the 108 women who completed at least six months of the study, or became pregnant during the first six months, the FFF program generated a difference of 14.2 percentage points in the live-birth rate (51% for the FFF group and 36.8% for the control group). The spontaneous pregnancy rate (pregnancy without any fertility treatments) was 33.3% in the treatment group, compared with 12.3% in the control group.

The researchers estimate the cost per additional newborn resulting from the FFF program at $12,633 (in 2019 Canadian dollars), somewhat similar to the willingness-to-pay for a newborn resulting from in vitro fertilization, which can cost up to $15,000.

"We hope this research will give women with obesity and infertility affordable access to a tailored lifestyle intervention adapted to their condition and their specific needs in order to improve their chances of having a pregnancy and building a family," Belan said.

WASHINGTON--Transgender youth have higher odds than cisgender youth of being diagnosed with medical conditions that can affect their overall metabolic and cardiovascular health, according to a study presented virtually at ENDO 2021, the Endocrine Society's annual meeting.

The study included 4,174 youth with a diagnosis of gender dysphoria, a term for a deep sense of unease and distress that may occur when a person's gender identity does not match their sex designated at birth. An estimated 1.8% of adolescents identify as transgender, according to lead researcher Anna Valentine, M.D., of the University of Colorado Anschutz Medical Campus, a provider at Children's Hospital Colorado in Aurora, Colo.

"This is the first study of its size in the United States of which we are aware that looks at the odds of youth with a diagnosis of gender dysphoria having medical diagnoses that relate to overall metabolic and cardiovascular health," Valentine said.

The researchers compared transgender youth with a diagnosis of gender dysphoria to 16,651 control youth without a diagnosis of gender dysphoria. The study calculated the odds of having overweight/obesity, high blood pressure, abnormal levels of cholesterol, high blood sugar levels, liver dysfunction and polycystic ovary syndrome. The authors first looked at the odds of having a diagnosis of one of these conditions listed in the chart, and then looked at diagnoses along with an objective body mass index from the weight/height in the chart, actual blood pressure measurements or objective laboratory measures.

When looking at diagnosis/billing codes with objective measures listed in the chart, the study found that transgender youth were 1.8x as likely to have abnormal cholesterol levels, 1.4x as likely to have liver dysfunction and 1.3x as likely to have high blood pressure when compared with cisgender youth. Transgender males were 1.5x as likely to be overweight or obese, and 1.9x as likely to have polycystic ovary syndrome, a common hormonal disorder that affects metabolic and reproductive health.

"As research in pediatric transgender medicine is emerging, showing what medical conditions are being diagnosed more often in this population can help individuals, families and health care providers better manage their health," Valentine said.

WASHINGTON--Black women with polycystic ovary syndrome (PCOS) have higher risk factors for heart disease, diabetes and stroke compared with white women, according to a study presented virtually at ENDO 2021, the Endocrine Society's annual meeting.

PCOS is a common disorder characterized by irregular menstrual periods, disruption of normal metabolism and excessive hair growth. PCOS affects up to 10% of all women of reproductive age. The disorder increases the risk for health conditions including infertility, obesity, heart disease, type 2 diabetes, depression and certain cancers.

"We found a disproportionate risk for health complications in Black women with PCOS in the United States, highlighting the need to fully identify and address health disparities in women with PCOS," said lead researcher Maryam Kazemi, Ph.D., a Postdoctoral Associate in Professor Marla Lujan's laboratory in the Division of Nutritional Sciences at Cornell University in Ithaca, N.Y.

Most PCOS research has focused on white women, Kazemi said. In order to find out whether Black women with PCOS share the same health risks, she conducted a systematic review of all available data on the risk of heart disease, diabetes and stroke, known collectively as cardiometabolic disease, to look for health disparities between Black and white women with PCOS in the United States. The review included 11 studies, with a total of 2,851 women (652 Black and 2,199 white).

The analysis found Black women with PCOS have a poorer cardiometabolic risk profile than white women, including higher insulin levels and more insulin resistance (risk factors for diabetes), and increased blood pressure, despite lower triglyceride levels than white women.

"Our findings support the need to increase public awareness about the disproportionate burden of cardiometabolic risk in young Black women with PCOS," said Kazemi. "These findings have implications for improving the sensitivity of clinical assessments in Black women to avoid underestimating cardiovascular risk in women with PCOS."

WASHINGTON--Endogenous Cushing's syndrome, a rare hormonal disorder, is associated with a threefold increase in death, primarily due to cardiovascular disease and infection, according to a study whose results will be presented at ENDO 2021, the Endocrine Society's annual meeting.

The research, according to the study authors, is the largest systematic review and meta-analysis to date of studies of endogenous (meaning "inside your body") Cushing's syndrome. Whereas Cushing's syndrome most often results from external factors--taking cortisol-like medications such as prednisone--the endogenous type occurs when the body overproduces the hormone cortisol, affecting multiple bodily systems.

Accurate data on the mortality and specific causes of death in people with endogenous Cushing's syndrome are lacking, said the study's lead author, Padiporn Limumpornpetch, M.D., an endocrinologist from Prince of Songkla University, Thailand and Ph.D. student at the University of Leeds in Leeds, U.K. The study analyzed death data from more than 19,000 patients in 92 studies published through January 2021.

"Our results found that death rates have fallen since 2000 but are still unacceptably high," Limumpornpetch said.

Cushing's syndrome affects many parts of the body because cortisol responds to stress, maintains blood pressure and cardiovascular function, regulates blood sugar and keeps the immune system in check. The most common cause of endogenous Cushing's syndrome is a tumor of the pituitary gland called Cushing's disease, but another cause is a usually benign tumor of the adrenal glands called adrenal Cushing's syndrome. All patients in this study had noncancerous tumors, according to Limumpornpetch.

Overall, the proportion of death from all study cohorts was 5 percent, the researchers reported. The standardized mortality ratio--the ratio of observed deaths in the study group to expected deaths in the general population matched by age and sex--was 3:1, indicating a threefold increase in deaths, she stated.

This mortality ratio was reportedly higher in patients with adrenal Cushing's syndrome versus Cushing's disease and in patients who had active disease versus those in remission. The standardized mortality ratio also was worse in patients with Cushing's disease with larger tumors versus very small tumors (macroadenomas versus microadenomas).

On the positive side, mortality rates were lower after 2000 versus before then, which Limumpornpetch attributed to advances in diagnosis, operative techniques and medico-surgical care.

More than half of observed deaths were due to heart disease (24.7 percent), infections (14.4 percent), cerebrovascular diseases such as stroke or aneurysm (9.4 percent) or blood clots in a vein, known as thromboembolism (4.2 percent).

"The causes of death highlight the need for aggressive management of cardiovascular risk, prevention of thromboembolism and good infection control and emphasize the need to achieve disease remission, normalizing cortisol levels," she said.

Surgery is the mainstay of initial treatment of Cushing's syndrome. If an operation to remove the tumor fails to put the disease in remission, other treatments are available, such as medications.

Study co-author Victoria Nyaga, Ph.D., of the Belgian Cancer Centre in Brussels, Belgium, developed the Metapreg statistical analysis program used in this study.

WASHINGTON--In adults with obesity or overweight, weekly treatment with the glucagon-like peptide 1 (GLP1) receptor agonist semaglutide leads to reduced excess body fat and increased lean body mass, according to an industry-sponsored study presented virtually at ENDO 2021, the Endocrine Society's annual meeting.

"Our findings suggest that semaglutide, through body weight loss and improvement of body composition, has the potential to reduce the risk of heart disease, diabetes and stroke in people with overweight or obesity," said lead researcher John Wilding, D.M., F.R.C.P., of the University of Liverpool.

Obesity poses many health risks. Excess fat in the abdominal area, particularly fat in and around abdominal organs, also called visceral fat, contributes to major causes of death and disability, including heart attacks, strokes, high blood pressure, cancer, fatty liver disease and diabetes.

The study, called STEP 1, included 1,961 adults with a body mass index (BMI) of 27 or higher with at least one weight-related health condition, or a BMI of 30 or higher, without diabetes. A person is classified as overweight if their BMI is 25 to 29.9, and the range for obesity is a BMI of 30 or more.

The study participants were randomly assigned to inject themselves once weekly for 68 weeks with either 2.4 milligrams of semaglutide or a placebo. Semaglutide, already approved by the U.S. Food and Drug Administration at the lower dose of 1 mg weekly as a treatment for type 2 diabetes, is a synthetic version of the naturally occurring hormone glucagon-like peptide 1 (GLP1). It acts on appetite centers in the brain and in the gut, and produces feelings of fullness.

As part of the study, the researchers used dual-energy absorptiometry (DEXA), a technique that is widely used clinically to assess body composition, to monitor the effects of therapy on total body fat and fat around the stomach area in 140 of the participants.

They found treatment with semaglutide improved body composition by reducing excess body fat, including abdominal fat, and increasing the proportion of lean body mass, or the amount of weight someone carries that is not body fat. The more body weight a participant lost, the greater the improvement in body composition.

In February 2021, the researchers published findings from the STEP 1 trial in The New England Journal of Medicine showing that patients who injected semaglutide lost close to 15% of their body weight, on average, compared with 2.4% among patients receiving the placebo. More than one-third of participants receiving semaglutide lost more than 20% of their weight. Many patients experienced improvements in risk factors for heart disease, blood sugar levels and quality of life.

WASHINGTON--Commonly used medications for type 2 diabetes and obesity called glucagon like peptide-1 receptor agonists (GLP-1 RAs), are not associated with an increased risk of breast cancer, despite previous studies that suggested a possible link, according to a study presented virtually at ENDO 2021, the Endocrine Society's annual meeting.

"GLP-1RAs can be used as adjunct to diet and exercise in subjects with type 2 diabetes and those without type 2 diabetes and excess weight, without an increased risk of breast cancer or noncancerous masses in the breast," said lead researcher Giovana Fagundes Piccoli, M.D., of the Universidade Federal do Rio Grande do Sul in Brazil.

GLP-1 RAs have been shown to be effective in treating obesity and type 2 diabetes and in reducing heart disease. These drugs include albiglutide (Tanzeum); dulaglutide (Trulicity); exenatide (Byetta); extended-release exenatide (Bydureon); liraglutide (Victoza, Saxenda); lixisenatide (Adlyxin); and semaglutide (Ozempic, Rybelsus). In clinical trials of liraglutide, subjects treated with the active drug instead of a placebo had a higher number of breast cancers. The new study was designed to assess whether patients treated with GLP-1 RAs had a higher risk of breast cancer or benign growths in the breasts called neoplasms.

Piccoli reviewed 52 randomized controlled trials that compared GLP-1 RAs with non-GLP-1 RAs (either other diabetes or weight-loss drugs or placebos) in adults with overweight, obesity, prediabetes or diabetes. The studies had a minimum follow-up period of 24 weeks and reported at least one event of breast cancer or benign breast neoplasm. They included a total of 90,360 participants.

The analysis found treatment with GLP-1 RAs was not associated with increased rates of breast cancer or benign or premalignant breast neoplasms, compared to placebo or other diabetes or weight-loss drugs. Among 48,267 subjects treated with GLP-1 RAs, 130 developed breast cancer, compared to 107 of 40,755 controls.

WASHINGTON--More patients than previously reported may experience hearing symptoms such as hearing loss or muffled hearing from a new treatment for thyroid eye disease, teprotumumab (Tepezza), according to a small study presented virtually at ENDO 2021, the Endocrine Society's annual meeting.

Teprotumumab, approved by the U.S. Food and Drug Administration in January 2020, is the first and only drug to be approved for thyroid eye disease. In two clinical trials conducted prior to FDA approval of the drug, otologic symptoms were reported in 10 percent of patients. The new study found the rate could be as high as 65 percent.

The treatment is administered to patients once every three weeks for a total of eight infusions. It has shown significant improvement in abnormal protrusion of the eyes (proptosis), double vision, soft tissue inflammation and quality of life.

Andrea Lora Kossler, M.D., assistant professor of ophthalmology at the Stanford University School of Medicine, is the senior author on the research. She and fellow researchers state that teprotumumab is an effective therapy for thyroid eye disease, but as with all therapeutics, there are known risks, including hearing impairment. The authors aim to better understand the risk of hearing loss and recommend tests to reduce this risk.

Thyroid eye disease is an autoimmune disease in which the eye muscles and fatty tissue behind the eye become inflamed. Symptoms can include dry, watery, red or bulging eyes, a "stare," double vision, difficulty closing the eyes, and problems with vision. It is primarily associated with an overactive thyroid gland due to Graves' disease.

To explore the incidence of hearing symptoms in patients treated with teprotumumab, the researchers evaluated 26 patients treated with at least four infusions of the drug. Seventeen patients (65 percent) complained of otologic symptoms when questioned. The most common symptoms were subjective hearing loss (n=6, 23 percent), tinnitus, or ringing in the ears (n=7, 27 percent), ear plugging sensation (n=3, 12 percent), and autophony, an unusually loud hearing of a person's own voice (29 percent). Otologic symptoms developed after an average of 3.6 infusions.

Of the 17 patients with new hearing symptoms, four had new or worsening sensorineural hearing loss, a type of hearing loss resulting from damaged hair cells in the inner ear. Three patients had patulous eustachian tube, a disorder in which the channel that runs between the middle ear and back of the nose and throat stays open. Normally, these eustachian tubes remain closed and open only occasionally to regulate air pressure around the ear drum. After three months, symptoms of patulous eustachian tube improved, but did not completely disappear. Two patients with sensorineural hearing loss had improvement in symptoms at one and six months.

The authors aim to raise awareness on the incidence of otologic symptoms & recommend screening precautions, such as baseline audiogram testing to better understand this potential side effect. The follow up period of 3 months after stopping the drug is too short to assess the reported reversibility of otologic symptoms. Future studies will evaluate risk factors for hearing loss and the reversibility of symptoms.

Researchers from Columbia University and Temple University published a new paper in the Journal of Marketing that examines how choice architecture can reduce socioeconomic disparities.

The study, forthcoming in the Journal of Marketing, is titled "Do Nudges Reduce Disparities? Choice Architecture Compensates for Low Consumer Knowledge" and is authored by Kellen Mrkva, Nathaniel Posner, Crystal Reeck, and Eric Johnson.

As Mrkva explains, "Our research demonstrates that people with low socioeconomic status (SES), low numerical ability, and low knowledge are most impacted by nudges. As a result, 'good nudges,' designed to encourage selection of options that are in people's best interests, reduce SES disparities, helping low-SES people more than high-SES people." On the other hand, nudges that encourage selection of inferior options exacerbate disparities relative to "good nudges" because low-SES consumers are more likely to retain inferior default options. In other words, nudges are a double-edged sword that can either reduce disparities or make matters worse because they impact low-SES people most. The research team generalized its findings across three different types of nudges, several different consumer decision contexts, and real retirement decisions.

This research has major implications, including for the COVID vaccination process. Across the country, millions of people are now eligible to get a COVID vaccine. However, the signup process is often unnecessarily complex. New York's nycHealthy sign-up portal, for example, includes as many as 51 questions and requests that you upload your insurance card. As a result, many people, especially the elderly, poor, and less digitally literate, have struggled or failed to make an appointment. As Johnson explains, "Our research suggests that making beneficial behaviors like vaccination simpler has a crucial and underappreciated advantage--it reduces socioeconomic disparities. On the other hand, when these behaviors are unnecessarily complex, it is typically low-SES consumers who are harmed the most."

In five experiments as well as data from real retirement decisions, the researchers show that people who are lower in SES, domain knowledge, and numeracy are impacted more by a variety of nudges. As a result, "good nudges" that facilitate selection of welfare-enhancing options reduce disparities by helping low-SES, low-knowledge, and low-numeracy consumers most.

In Study 1, participants made five consumer financial decisions. For each decision, they were randomly assigned to a "no default," "good default," or "bad default" condition (the latter two pre-selected correct or incorrect options, respectively). After they made these five decisions, participants completed common measures of the three hypothesized moderators--financial literacy, numeracy, and socioeconomic status. As predicted, there was a large default effect. There were also interactions between the default condition and the three moderators; participants lower in these moderators were more impacted by defaults. These effects remained significant when adding survey engagement, comprehension, need for cognition, agreeableness, decision time, and their interactions with condition to the model as covariates.

Study 2 examines whether these effects generalized across three different types of nudges and three decision contexts. It replicated the SES and financial literacy effects of Study 1 across all nudges and contexts. Unlike Study 1 and all subsequent studies, the nudge x numeracy interaction was not significant. The key effects remained significant when controlling for a measure of fluid intelligence.

Study 3 uses syndicated data from stratified random samples of American households about their retirement investment decisions to examine a sample of people who work for companies that use defaults to automatically enroll employees into retirement contributions. Respondents reported whether they retained or opted out of the default contribution amount and default investment allocation. Evidence supports that lower-SES and less financially literate people are more impacted by nudges and thus less likely to opt out of these retirement defaults: Lower-SES participants were less likely to opt out as were participants with lower financial literacy.

Study 4 replicated these effects in the context of COVID-19 health decisions (e.g., deciding whether to wear a mask). Additionally, domain-specific health knowledge moderated default effects whereas other-domain knowledge did not. Studies 5-6 replicated the predicted moderators from Study 1 with incentives. Mediation models suggest that people with lower SES, domain knowledge, and numeracy were more impacted by nudges partly because they experience higher uncertainty and decision anxiety when making decisions.

Across the six studies, nudges influenced choice disparities across people. Posner summarizes the study by saying "Our results suggest that nudges that make behaviors such as retail purchases, vaccine sign-up, and retirement contributions more automatic can reduce socioeconomic inequities."

BOSTON - Researchers have used a genetic engineering strategy to dramatically reduce levels of tau--a key protein that accumulates and becomes tangled in the brain during the development of Alzheimer's disease--in an animal model of the condition. The results, which come from investigators at Massachusetts General Hospital (MGH) and Sangamo Therapeutics Inc., could lead to a potentially promising treatment for patients with this devastating illness.

As described in Science Advances, the strategy involves a gene regulation technology called zinc finger protein transcription factors (ZFP-TFs), which are DNA-binding proteins that can be harnessed to target and affect the expression of specified genes. In this case, the therapy was designed to target and silence the expression of the gene that codes for tau. Mice with Alzheimer's disease received a single injection of the treatment--which employed a harmless virus to deliver the ZFP-TFs to cells--directly into the hippocampus region of the brain or intravenously into a blood vessel. Treatment with ZFP-TFs reduced tau protein levels in the brain by 50% to 80% out to 11 months, the longest time point studied. Importantly, the therapy reversed some of the Alzheimer's-related damage that was present in the animals' brain cells.

"The technology worked just the way we had hoped--reducing tau substantially for as long as we looked, causing no side effects that we could see even over many, many months, and improving the pathological changes in the brains of the animals," says senior author Bradley Hyman, MD, PhD, who directs the Alzheimer's disease research unit at the MassGeneral Institute for Neurodegenerative Disease. "This suggests a plan forward to try to help patients."

The simplicity of the therapy makes it an especially attractive approach. "This was the result of a single treatment of gene regulation therapy, which could be given by an injection into the bloodstream," says Hyman. "While this therapy is far from patients--as much more development and safety testing would need to be done--it is a promising and exciting first step."

In a recent study testing the effects of exercise on overall metabolism, researchers at Oregon State University found that even a single session of moderate aerobic exercise makes a difference in the cells of otherwise sedentary people.

Mitochondria are the part of the cell responsible for the biological process of respiration, which turns fuels such as sugars and fats into energy, so the researchers focused only on mitochondria function.

"What we found is that, regardless of what fuel the mitochondria were using, there were mild increases in the ability to burn off the fuels," said Matt Robinson, lead author on the study and an assistant professor in the College of Public Health and Human Sciences.

OSU researchers recruited participants who do not follow a regular exercise routine and had them ride a stationary bike for an hour at a moderate intensity. They biopsied their muscles 15 minutes later to test how efficient the mitochondria were after the exercise was completed and compared those results with a resting day.

Post-exercise, study participants' mitochondria burned 12-13% more fat-based fuel and 14-17% more sugar-based fuel. While the effects were not drastic, they were consistent, Robinson said.

"It's pretty remarkable that even after just one hour of exercise, these people were able to burn off a little more fuel," he said.

Previous research in the field has long established that regular exercise creates lasting change in people's metabolism, making their bodies burn more energy even when they're not working out.

Prior studies have looked at highly trained or athletic people, but Robinson's team wanted to look specifically at singular bouts of exercise in people who were generally active and disease-free but who did not have structured exercise regimes. These people were on the lower end of fitness, which is associated with low mitochondrial abundance and energy production. Participants were monitored while working out at approximately 65% of their maximal effort, where they could keep up the cycling pace for an hour or more and still comfortably carry on a conversation.

Robinson said they're hoping these results help break down the mental barrier of people thinking they need to be elite athletes for exercise to make an impact on their health.

"From a big picture health perspective, it's very encouraging for people to realize that you can get health benefits from a single session of exercise," Robinson said. "We're trying to encourage people, 'You did one, why don't you try to do two? Let's do three.'

"We know that exercise is good for you, in general. But those benefits of that single bout of exercise seem to fade away after a day or two. You get the long-term benefits when you do that exercise again and again and you make it a regular habit."

In this study, Robinson's research team focused narrowly on mitochondria to find out how big a role mitochondria play in the overall function of muscle metabolism. Other studies are looking at changes in blood flow to the muscle and how the muscle metabolizes fats versus sugars.

From a disease perspective, Robinson said it's clear that obesity and diabetes involve impairments in metabolism. Physiologically, when the body undergoes exercise, sugars tend to be burned off first while fats are stored, but in cases of diabetes and obesity, there is some dysregulation in metabolism that causes the body to not be able to switch between the two types of fuel.

Exercise can help reset that system, he said.

"Since those get burned off in the mitochondria, our hope is that with exercise, we could increase the mitochondria and then improve how the body burns off fats and sugars," he said.

PITTSBURGH, March 19, 2021 - A University of Pittsburgh School of Medicine-led survey of dozens of surge capacity managers at hospitals nationwide captures the U.S. health care system's pandemic preparedness status in the months before the first COVID-19 cases were identified in China.

Published today in the journal JAMA Network Open, the investigation details the strain experienced by U.S. hospitals during the 2017-18 influenza season, which was marked by severe illness and the highest infectious disease-related hospitalization rates in at least a decade. At the time, pandemic planning within hospitals was not reported as being a high priority.

"The timing for our survey couldn't have been better--ultimately it serves as a pre-COVID-19 time capsule of our preparedness to accommodate surges in patients needing hospitalization for acute illness," said senior author David Wallace, M.D., M.P.H., associate professor in Pitt's departments of Critical Care Medicine and Emergency Medicine. "It was surprising to hear very detailed stories of the strain hospitals were under during the 2017-18 flu season, and yet have no pandemic planning come out of it."

The 2017-18 flu season was associated with more than 27.7 million medical visits, nearly a million hospitalizations and almost 80,000 deaths, according to the U.S. Centers for Disease Control and Prevention. That is more than double the deaths in a typical flu season and the highest hospitalization rate since seasonal influenza surveillance was instituted in 2005.

Wallace and his team--which included specialists in health policy, medical anthropology and infectious diseases--interviewed surge capacity managers at a random sampling of 53 hospitals across the U.S. starting in April 2018, at the tail end of the flu season. Using a structured survey, they recorded detailed interviews about everything from ICU bed capacity and staffing ratios to the perceived effect of strain on quality of patient care and staff well-being.

All of those surveyed reported experiencing hospital strain during the 2017-18 flu season. Strain was generally described as the result of high patient occupancy causing demand to outstrip the supply of resources--in fact or in perception.

The "4 S's"--staff, stuff, space and systems--were reported as the widespread challenges that surge capacity managers consistently faced in continuing health care operations during the flu season. Staff was a particular concern, due to fatigue or staff being out sick with flu or caring for ill family.

"This demonstrates that the perceptions of strain on staffing, patient care and capacity that we have seen during the COVID-19 pandemic were already present with prior epidemics," said lead author Gavin Harris, M.D., an assistant professor in the Emory University School of Medicine, who did this research while at Pitt. "Less than two years before COVID-19 took off in the U.S., we were experiencing a preview of the strain that a fast-spreading, severe respiratory infection places on our health system."

In fall 2013--four years before this challenging flu season--the U.S. Department of Health and Human Services Office of the Assistant Secretary for Preparedness and Response produced the Interim Healthcare Coalition Checklist for Pandemic Planning report, which identified eight categories hospitals should address when planning for crises, specifically surges in acute care needs. None of the survey participants commented on all eight categories, nor did any specifically report using the checklist.

"Hospitals have a tendency to deal with what's right in front of them, the present," Wallace said. "In doing that, we must also learn when certain levers--like a pandemic preparedness checklist--must be pulled. That is done through reflecting after a crisis subsides and looking for opportunities to improve before the next crisis hits. If the past year has taught us anything, it's that infectious diseases aren't going away, and we'll always get a chance to put lessons learned to work."

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in pregnancy is associated with preeclampsia, stillbirth, preterm birth and other adverse outcomes, found new research published in CMAJ (Canadian Medical Association Journal) .

"Our findings suggest that pregnant people with COVID-19 have an increased risk of high blood pressure, stillbirth and preterm birth. Their newborns are more likely to need intensive care. Pregnant people with severe COVID-19 symptoms have a particularly high risk of these complications," says Dr. Nathalie Auger, Department of Social and Preventive Medicine, School of Public Health, University of Montreal, Montréal, Quebec, with coauthors.

Researchers reviewed 42 studies involving 438 548 pregnant people from around the world to determine the association between SARS-CoV-2 infection and adverse pregnancy outcomes. They found double the risk of preterm birth and a 50% increased risk of cesarean delivery in pregnant people with symptomatic COVID-19 than in those with asymptomatic COVID-19. Those with severe COVID-19 had a 4-fold higher risk of high blood pressure and preterm birth.

The reason for the increased risk of adverse outcomes is unclear, but could be because SARS-CoV-2 may lead to vasoconstriction and stimulate an inflammatory response affecting blood vessels.

The findings of this systematic review differ from prior findings from case reports and case series. "Our meta-analysis of recent good-quality cohort studies with comparative data does not align with these previous reviews, and provides clear evidence that symptomatic or severe COVID-19 is associated with a considerable risk of preeclampsia, preterm birth and low birth weight," write the authors.

"Clinicians should be aware of these adverse outcomes when managing pregnancies affected by COVID-19 and adopt effective strategies to prevent or reduce risks to patients and fetuses," they conclude.

TROY, N.Y. -- A novel form of polymerized estrogen developed at Rensselaer Polytechnic Institute can provide neuroprotection when implanted at the site of a spinal cord injury -- preventing further damage. This promising result, found in a preclinical model, was recently published in ACS Chemical Neuroscience, and it lays the groundwork for further advancement of this new biomaterial.

"What we saw that gives us hope is more neuroprotection, meaning we saw more spared neurons and more spared axons in the tissue," said Ryan Gilbert, a professor of biomedical engineering at Rensselaer, and co-author on this paper. "We believe that the estrogen released from our biomaterial design is providing a neuroprotective response."

After a spinal cord injury, the body's inflammatory response can cause further damage to nervous system cells -- like a loss of neurons and axons -- even beyond the site of initial injury. A solution that could prevent additional deterioration, or even promote regeneration over time, could be a paradigm shift in treatment. Estrogen is a natural hormone produced within the body. When polymerized, it shows promise as a source of neuroprotection following a spinal cord injury.

Gilbert, a member of the Center for Biotechnology and Interdisciplinary Studies at Rensselaer, collaborated with Edmund Palermo, an associate professor of materials science and engineering at Rensselaer, to design this polymer. The preclinical aspect was initiated by Manoj Gottipati, a Rensselaer research associate, currently working in the laboratory of Phillip Popovich, professor and chair of the Department of Neuroscience at The Ohio State University. At Ohio State, Gottipati worked with Zhen Guan from the Center for Brain and Spinal Cord Repair to test the polymerized estrogen film. The researchers observed enhanced neuroprotection in a preclinical mouse model that had the implanted polymerized estrogen when compared to models that did not receive this treatment.

The polymer itself is entirely made of estrogen, which is released slowly within the body over time as water reactions break down the bonds that hold the polymer chain together, making it a unique and promising therapeutic approach.

"Since the drug molecule is enchained in every repeating unit of the long chain, it contains a very high drug load compared to conventional delivery approaches," said Palermo, who is also co-author on this paper and a member of the Rensselaer Center for Materials, Devices, and Integrated Systems.

According to Palermo, the polymer studied in this research is one of a number of candidates the researchers will continue to investigate as they work to find the optimal release rate for enhanced neuroprotection. Finely tuning hydrophobicity, mechanical properties, and hydrolysis rates could all make a difference in critical aspects of its performance, such as how quickly the polymer releases estrogen within the body.

"All of those factors will play a role in the complex cascade of biochemical and biophysical events that occur during the course of the body's reaction to spinal cord injury," Palermo said.

As the team continues to modify this biomaterial, what researchers develop could have implications beyond spinal cord injury therapeutics.

"I would say that this approach could be used for any sort of central nervous system injury, from spinal cord to brain injury," Gilbert said. "Anything where we could inject or place it near the injury site and have that therapy be released for an extended duration."

During a public health crisis like the COVID-19 pandemic, U.S. hospitals need to allocate scarce medical resources in an equitable manner, according to clinicians and ethicists at the University of Miami Miller School of Medicine.

"Significant concerns have been raised that crisis standards of care may be biased against certain patients based on race or ethnicity," said Hayley Gershengorn, M.D., associate professor of pulmonary and critical care medicine. "To examine that issue, we analyzed over a thousand medical records from two academic hospitals where University of Miami faculty see patients and found no disparities in how our crisis standards of care policy prioritizes patients."

Dr. Gershengorn was the lead author of the study, "Assessment of the Disparities Associated With a Crisis Standards of Care Resource Allocation Algorithm for Patients in Two U.S. Hospitals During the COVID-19 Pandemic," published March 11 in JAMA Network Open, a journal of the American Medical Association.

"Early in the pandemic, we became concerned that demand for hospital resources such as ventilators would be greater than availability," she said. "A crisis policy can help physicians allocate resources in such circumstances."

To address those ethical issues, a Miller School team developed a Crisis Standards of Care policy that was approved by the university and now serves as a model for other members of the Florida Hospital Association, said Dr. Gershengorn. "After approving the policy, we felt it was also important to see how well the policy could be put into practice," she added.

The critical care faculty recruited third-year Miller School students to go through the medical records daily and calculate priorities based on the sequential organ failure assessment (SOFA) score, which measures patient acuity, and comorbidity burden. "This study would not have been possible without our students," said Dr. Gershengorn. "They did an amazing job."

The new study asked the question: Is there an association of race or ethnicity with priority scores used for resource allocation under our institution's crisis standards of care policy? The researchers looked at 1,127 adult patients (with 5,613 patient-days of data) who were admitted to one of the COVID-19 wards or were in a monitored unit requiring invasive or noninvasive ventilation or high-flow nasal cannula between May 26 and July 14, 2020.

"We found the priority score did not appear to discriminate against hospitalized patients based on self-identified Black race or Hispanic ethnicity," said Dr. Gershengorn.

Co-author Kenneth W. Goodman, Ph.D., director of the University of Miami Institute for Bioethics and Health Policy, said, "In a time of too much bad news, these results are very good news. We found that our resource allocation protocol would - if activated - not worsen existing inequities for Black and Hispanic populations when it comes to COVID-19."

Another co-author, Jeffrey P. Brosco, M.D., Ph.D., professor of pediatrics and the Institute's director of population health ethics, added, "We need to redouble our efforts to improve health equity, and one way is for health care providers to use data as we did to examine the effects of our policies and procedures."

Other Miller School co-authors included Gregory E. Holt, M.D., Ph.D., assistant professor of medicine; Joseph West, Sc.M., Sc.D. , voluntary assistant professor of public health science; Daniel H. Kett, M.D., professor of clinical medicine and associate chief medical officer for critical care at the University of Miami Hospital, as well as Miller School students Andrew Rezk, Stefanie Delgado, Nayna Shah, Arshia Arora, Leah B. Colucci, MS, Belen Mora, Rahul S. Iyengar, MHA, Andy Lopez, and Bianca M. Martinez.

Rezk, M.D. Candidate, Class of 2021, organized the data collection at the two academic hospitals with other students. "What I learned in this study is the importance of not just being aware of unintended health disparities but actively acknowledging them because these are life or death decisions that can affect an entire race or ethnicity," he said.

Another member of the Class of 2021, Delgado contributed to generating a protocol for the study, as well as training and supervising medical student volunteers. "The importance of acknowledging and addressing health disparities is imperative if we are to practice effective and equitable healthcare to all," she said. "The more we are aware of possible and existing disparities, the better prepared we are to identify and address associated obstacles which will ultimately lead to a better patient physician interaction and hopefully better health outcomes as well."