Experts describe types of rashes associated with MIS-C

CHOP experts describe types of rashes associated with MIS-C

In April 2020, pediatricians began recognizing a puzzling syndrome in children involving hyperinflammation that results in an array of symptoms, including fever, gastrointestinal distress and rash. The syndrome, thought to be a post-infectious complication of SARS-CoV-2 infection, was given the name Multisystem Inflammatory Syndrome Children, or MIS-C. However, diagnosing the condition has posed challenges, as many of its symptoms, including rash, are common in many other pediatric infections.

In a study published in Open Forum Infectious Diseases, researchers at Children’s Hospital of Philadelphia (CHOP) describe the array of rashes seen in MIS-C patients at their hospital through late July 2020, providing photos and information that could help doctors diagnose future cases.

“We hope the information provided in this research letter will help general pediatricians and emergency department physicians who may wonder if a patient with a fever requires a more extensive examination,” said Audrey Odom John, MD, Ph.D., Chief of the Division of Pediatric Infectious Diseases at CHOP and senior author of the paper. “Given that some rashes associated with MIS-C are distinctive, we also imagine these images could help many parents who are looking for signs that their child needs prompt evaluation.”

The research team analyzed the MIS-C-associated rashes of seven patients seen at CHOP. Although the researchers did not observe a single, defining rash associated with COVID-19, there were several types of rashes that were common in these patients, both in appearance and location.

In terms of rash location, all patients in the study developed a rash on their lower body, and five of the seven patients had a rash on their inner thighs. Rashes on the chest and upper extremities were also common, occurring in four out of seven patients.

More than half of the patients presented with small-to-medium annular plaques, which look like dime-size circles, on their chest and back. More than half of the patients in the study also developed purpura, tiny red spots, often in the center of the dime-like annular plaques.

While some patients did develop a cherry-red rash on the bottoms of their feet and palms of their hands, this sort of rash was seen in less than half of the patients in the study. Rashes on the face were uncommon, and the rashes rarely itched.

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Hypertension at Middle Age Associated With Cognitive Decline

WEDNESDAY, Dec. 16, 2020 — Hypertension at younger or older middle ages is associated with cognitive decline in different abilities, according to a study published online Dec. 14 in Hypertension.

Sara Teles de Menezes, Ph.D., from Universidade Federal de Minas Gerais in Belo Horizonte, Brazil, and colleagues conducted a longitudinal study involving 7,063 participants in the ELSA-Brasil cohort (mean age, 58.9 years at baseline in 2008 to 2010) who attended visit 2 in 2012 to 2014. At both visits, cognitive performance was measured and assessed using standardized scores of memory, verbal fluency, trail B tests, and the global cognitive score.

The researchers found that hypertension and prehypertension at baseline correlated with a reduction in the global cognitive score; hypertension correlated with a decline on the memory test; and prehypertension correlated with a decrease on the fluency test. Lower global cognitive and memory scores were seen with hypertension diagnosed at 55 years or older, while lower memory test scores were seen for hypertension diagnosed at younger than 55 years. There was no correlation observed for duration of hypertension diagnoses with any marker of cognitive function decline. There was an inverse correlation seen for blood pressure control at baseline with decline in both global cognitive and memory test scores among treated individuals.

“Our results highlight the importance of diagnosing and controlling hypertension in patients of any age to prevent or slow down cognitive decline,” a coauthor said in a statement. “Our results also reinforce the need to maintain lower blood pressure levels throughout life, since even prehypertension levels were associated with cognitive decline.”

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Study on placenta membrane cells identifies genetic markers associated with preterm birth

A new research study from the March of Dimes Prematurity Research Center led by investigators at the University of Chicago has identified new genetic markers associated with gestational length, providing new insights into potential risk factors for preterm birth.

In a collaboration between multiple labs and funded through the March of Dimes Foundation, the investigators set out to map important gene regulatory regions and genetic markers relevant to preterm birth. Their first challenge was addressing the lack of functional genomics data in pregnancy-relevant tissue types.

“When you’re studying a disease, there are typically a lot of genetic and tissue resources available in public databases,” said co-senior author Carole Ober, Ph.D., Chair of Human Genetics at UChicago. “But pregnancy related conditions, like preterm birth, get much less attention or funding, and as a result pregnancy-relevant tissues are not well represented in those databases.”

The paper, published on Dec. 2, 2020 in Science Advances, focused on decidualized cells derived from the endometrial cells attached to the placenta. Decidualized cells line the uterus during the latter half of the menstrual cycle, preparing it for implantation and supporting the growth and development of the placenta and fetus throughout pregnancy.

The investigators collected placental tissue donated by patients who had given birth and isolated the decidualized cells in the lab. Genetic analysis of these cells identified two new candidate preterm birth genes, HAND2 and GATA2.

“These genes are both important transcription factors that regulate the expression of several other genes,” said co-first author Ivy Aneas, Ph.D., a research associate professor of human genetics at UChicago. “HAND2 mediates the effect of progesterone on the uterine epithelium while GATA2 is involved in stem cell maintenance.”

Both of these processes and the genes that control them are known to be important for endometrial decidualization and embryo implantation.

“The fact that we identified a link between these two genes and the duration of gestation suggests that their roles in pregnancy may be more important than previously anticipated,” said co-first author Noboru Sakabe, Ph.D., a staff scientist at UChicago.

Understanding how these genes contribute to the length of pregnancy could be a key to developing new preventions against preterm birth.

“Researchers have recognized a number of factors that can lead to preterm birth, ranging from environmental to infectious disease and beyond, but what is vexing is that we haven’t been successful in preventing it,” said co-senior author Marcelo Nobrega, MD, Ph.D., professor of human genetics at UChicago. “Our research took a look at the genetics and allowed us to pull out some links that might illuminate genetic pathways and signaling molecules involved in the decidualization process, which in turn might provide new targets for therapies.”

The researchers were able to leverage combined expertise in human genetics, genomics and statistical analysis to combine data gathered from human endometrial cells in the lab with data from existing genome-wide association studies (GWAS) to zero in on key genetic variations that may be linked to preterm birth.

“Only six or seven genomic regions have been linked to preterm birth and gestational length,” said co-senior author Xin He, Ph.D., assistant professor of human genetics at UChicago. “We don’t know which genes are involved or how that influences cell function and risk of preterm birth. With our approach, we integrated genomics data generated from our center and integrated it with other databases to identify the underlying genetic interactions. This can lead us to genes that may be involved in this condition, which gives us a hint to the underlying biology.”

While genetic factors are thought to play only a small role in the risk of preterm birth, the investigators were glad to see such clear results in their study.

“Preterm birth is so common, and some people experience it repeatedly,” said Ober. “If you have a preterm birth, it doesn’t matter if it’s genetic or not, you just don’t want to experience one again. We can now use this information to better understand some of the genetic component and how it plays a role in the condition.”

Future research will investigate other kinds of cells that may play key roles in pregnancy and preterm birth, such as the immune cells that reside at the maternal-fetal interface, and grow the “roadmap” of genomic variations in endometrial cells by examining the effects of varied environmental conditions on gene expression.

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Untreated sleep apnea is associated with flu hospitalization

As we approach flu season, adults with obstructive sleep apnea may want to take extra precautions. A study published online as an accepted paper in the Journal of Clinical Sleep Medicine is the first to find that patients with sleep apnea who did not use CPAP therapy were more likely to be hospitalized with the flu.

Results of the retrospective study show that 61% of patients (17 of 28) who either weren’t prescribed CPAP to treat their sleep apnea or weren’t adherent to their CPAP treatment were hospitalized with the flu, compared with 24% of patients (6 of 25) who were adherent to CPAP therapy. Statistical analysis found that the patients who were non-adherent to CPAP were nearly five times more likely to be hospitalized with a flu infection, despite having a higher rate of flu vaccination.

“Our study would suggest that among patients with obstructive sleep apnea, those who use CPAP are less likely to be hospitalized because of an influenza infection than those who do not use CPAP,” said study coinvestigator Dr. Glen Greenough, associate professor of medicine, psychiatry and neurology at the Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire.

Greenough said the study provides further evidence that sleep is essential to health.

“These results would suggest that use of a treatment, CPAP, that improves sleep quality reduces the severity of influenza infection as determined by rate of hospitalization,” he said. “This might suggest that treating sleep apnea and thereby improving sleep quality has a beneficial effect on the immune system. It also suggests that treating sleep apnea with CPAP could help reduce hospitalizations thereby reducing health care costs.”

Nearly 30 million adults in the U.S. have obstructive sleep apnea, a chronic disease that involves the repeated collapse of the upper airway during sleep. Common warning signs include snoring and excessive daytime sleepiness. A common treatment is CPAP therapy, which uses mild levels of air pressure, provided through a mask, to keep the throat open during sleep.

The researchers at Dartmouth-Hitchcock Medical Center analyzed the medical records of 53 patients who had sleep apnea and a confirmed case of the flu between 2016-2018. The 28 patients categorized as non-adherent to CPAP treatment had a mean age of 63 years and were 54% male; the 25 CPAP-adherent patients had a mean age of about 60 years and were 52% male. CPAP use was assessed by data download, with adherence defined as usage of at least four hours per night for at least 70% of nights.

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Study shows that rheumatoid arthritis is associated with a 23% increased risk of developing diabetes

A new study presented at this year’s annual meeting of the European Association for the Study of Diabetes (EASD), held online this year, shows that rheumatoid arthritis (RA) is associated with a 23% increased risk of type 2 diabetes (T2D), and may indicate that both diseases are linked to the body’s inflammatory response. The research was conducted by Zixing Tian and Dr. Adrian Heald, University of Manchester, UK, and colleagues.

Inflammation has emerged as a key factor in the onset and progression of T2D, and RA is an autoimmune and inflammatory disease. The team suggest that the systemic inflammation associated with RA might therefore contribute to the risk of an individual developing diabetes in the future.

The team conducted a comprehensive search of a range of medical and scientific databases up to 10 March 2020, for cohort studies comparing the incidence of T2D among people with RA to the diabetes risk within the general population. Statistical analyses were performed to calculate the relative risks, as well as to test for possible publication bias (in which the outcome of research influences the decision whether to publish it or not). The eligible studies identified comprised a total of 1,629,854 participants. Most of the studies were population-based and one was hospital-based, while no evidence was found for publication bias in any of them.

The authors found that having RA was associated with a 23% higher chance of developing T2D, compared to the diabetes risk within the general population. They conclude that: “This finding supports the notion that inflammatory pathways are involved in the pathogenesis of diabetes.”

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Interim data from early US COVID-19 hotspot show mortality of disease were not associated with race/ethnicity

A study of interim data from two hospitals in an early US COVID-19 hotspot, to be presented at the ESCMID Conference on Coronavirus Disease (ECCVID, held online 23-25 September), shows that race and ethnicity were not significantly associated with higher in-hospital COVID-19 mortality, and that rates of moderate, severe, and critical forms of COVID-19 were similar between racial and ethnic groups.

The study, by Dr. Daniel Chastain (University Of Georgia College Of Pharmacy, Albany, GA, U.S.) and colleagues included data from adult patients hospitalised between March 10 and and May 22 with COVID-19, defined by laboratory-detected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, in Southwest Georgia.

The authors compared severity of illness categories on presentation to the hospital between patients from different racial and ethnic groups based on criteria from the US National Institutes of Health (NIH) COVID-19 treatment guidelines. They also studied outcomes including comorbidities, laboratory values, vital signs, and in-hospital mortality.

A total of 164 randomly selected non-consecutive patients were included with a median age of 61.5 years. These consisted of 119 African American patients, 36 Caucasian patients, and 9 Latinx patients. Thus the majority were African American (73%) and 51% were female. Rates of moderate, severe, and critical COVID-19 did not significantly differ between African American (9%, 56%, and 35%), Caucasian (0%, 69%, and 31%), and Latinx patients (0%, 56%, and 44%). In-hospital mortality was not statistically significantly different between groups but was highest among Caucasians (31%) followed by Latinx (22%) and African Americans (16%).

Caucasian patients had significantly higher Charlson comorbidity index scores (meaning more underlying conditions) (4.5) compared to African American (4) and Latinx (2) patients, while median BMI was significantly higher in African Americans (33.7 kg/m2) than in Caucasians (26.9) or Latinx patients (25.9).

Duration of time from symptom onset to admission was similar between groups, whereas median temperature on admission was significantly higher in African Americans (38.3C) than in Caucasians (37.9) or Latinx patients (37.8)

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Smartphones can predict brain function associated with anxiety and depression

Information on social activity, screen time and location from smartphones can predict connectivity between regions of the brain that are responsible for emotion, according to a study from Dartmouth College.

In the research, data from phone usage was analyzed alongside results from fMRI scans to confirm that passively collected information can mirror activity in the brain linked to traits such as anxiety. Predictions based solely on the phone data matched the brain scans with 80 percent accuracy.

The study, presented at ACM UbiComp, an annual conference on pervasive and ubiquitous computing, represents the first time researchers have been able to predict connectivity between specific brain regions solely based on passive data from smartphones.

“Simple information about how someone is using their smartphone can provide a peek into the complex functioning of the human brain,” said Mikio Obuchi, a Ph.D. student in the Department of Computer Science at Dartmouth and lead author of the study. “Although this research is just beginning, combining data from smartphones—rather than fMRI alone—will hopefully accelerate research to understand better how the human brain works.”

According to the research, how often and how long an individual uses their phone provides information about the functioning between the ventromedial prefrontal cortex and the amygdala—two key centers of the brain related to emotional state.

The ventromedial prefrontal cortex is responsible for self-control, decision making, and risk evaluation. The amygdala triggers the fight or flight response and helps individuals determine the emotions of others.

In addition to data on social activity, screen time and location, information on exercise and sleep patterns was also collected for the study.

The research found that more screen time, regular exercise, earlier bedtimes, higher social interaction and certain location patterns passively inferred from phone data matched a state of higher functional connectivity between the brain regions. This increased activity indicates a more positive emotional state.

“We are not suggesting that phones should replace technology like fMRI, but they can help individuals and health providers learn more about behavior patterns from everyday observations,” said Jeremy Huckins, a lecturer on psychological and brain sciences at Dartmouth and a co-author of the study.

The research result aligns with clinical evidence showing that stronger connectivity between the ventromedial prefrontal cortex and the amygdala to be associated with lower levels of anxiety and depression. Weaker functional connectivity, on the other hand, represents a more negative emotional state.

Anonymous fMRI data from volunteer participants were placed into two categories divided by low and high brain connectivity levels. By matching phone data against the fMRI results the researchers were able to predict which research subjects had higher or lower connectivity between brain regions with 80 percent accuracy.

According to the research team, the use of passive information from a smartphone can help eliminate the subjectivity that often complicates other information-gathering techniques on emotional well-being such as personal interviews and self-reporting on questionnaires.

The phone information allowed researchers to predict the emotional state of individuals at any given time without intrusive data collection. The data also support predictions of the long-term emotional traits in individuals.

“Hopefully, this study shows how mobile sensing can provide deep longitudinal human behavioral data to complement brain scans,” said Andrew Campbell, the Albert Bradley 1915 Third Century Professor of computer science at Dartmouth and the senior researcher on the study. “This could offer new insights into the emotional well-being of subjects that would just not be possible without continuous sensing.”

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