Although the benefits of continuous glucose monitoring for patients with diabetes has been demonstrated before, the benefits have only been well studied in patients with type 1 diabetes or patients with type 2 treated with multiple daily insulin injections, referred to as prandial insulin.

Study author Rodica Busui, M.D., Ph.D., also the vice chair of clinical research in the Department of Internal Medicine at University of Michigan Health, says this work is one of the first to thoroughly understand the impact of having access to and using a continuous glucose monitor in adults with poorly controlled type 2 diabetes that are only treated with basal insulin, a long-acting insulin designed to be injected once or twice daily to provide an adequate level of insulin throughout the day and night

“Not only does this trial demonstrate the benefits of continuous glucose monitoring for these patients, a technology that hasn’t been covered by many insurers for those with type 2 diabetes, but these benefits were seen across a broad spectrum of socio-economic status and racial backgrounds,” said Busui.

She adds that approximately half of the study’s participants were of a racial or ethnic minority.

The randomized clinic trial began enrolling patients in mid-2018 to late-2019, with follow up in mid-2020. The participants received one or two daily injections of long-acting basal insulin, with or without non-insulin medications to help lower blood sugar levels.

“This work wouldn’t have been possible without the partnership between endocrinologists and primary care physicians, as all the patients were recruited and treated by our primary care teams,” said Busui, who is also associate director for clinical research in the Elizabeth Weiser Caswell Diabetes Institute.

Aside from testing the efficacy of continuous glucose monitoring paired with basal insulin in the study participants, Busui and her team sought to better understand how the impact of this diabetes treatment approach affected patients’ adherence to managing their disease as well as their overall life satisfaction.

To the researchers’ delight, the 175 study participants exhibited better adherence to managing their diabetes, and their life satisfaction was higher.

“For me, what’s most exciting is that this work demonstrates that using continuous glucose monitoring is effective in substantially improving blood sugars levels and decreasing the risks of hypoglycemia in those that were randomized to use a continuous glucose monitor compared with the usual finger-prick,” said Busui.

“This may open the door for broader coverage of this game-changing technology for all patients with diabetes. More patients can manage their diabetes if they have access to this resource and their primary care physicians are educated on the benefits of their patients utilizing it.”

This future of more affordable health care already looks a little bit brighter with Medicare recently announcing eliminating the requirement of the four-time-daily finger-prick to qualify for coverage of a continuous glucose monitor.

Work was contributed by several co-investigators at U-M, including Caroline Richardson, M.D., associate chair of research in the department of Family Medicine, Lynn Ang, M.D., and Kara Mizokami-Stout, M.D., assistant professors in the department of Metabolism, Endocrinology and Diabetes, as well as clinical trial coordinators Jake Reiss, B.S., Aaron Burant, B.S. and Ginny Leone, M.S.

This study was sponsored by DexCom, Inc. ClinicalTrials.gov Identifier: NCT03566693.

This unique observation prompted a collaborative study explained in a new paper published today in Nature Communications analyzing what this foggy water layer is caused by, and the impact it has on life at the bottom of the seafloor.

“What we’re seeing are hypoxic ocean waters, meaning there is little to no oxygen in that area. All of the macro-organisms are trying to get away from this deoxygenated water, and those that cannot escape essentially suffocate. I have never seen anything like that on a coral reef,” said Johnson.

“There is a combination of stagnant water from low wind activity, warm water temperatures, and nutrient pollution from nearby plantations, which contributes to a stratification of the water column. From this, we see these hypoxic conditions form that start to expand and infringe on nearby shallow habitats,” explained Johnson.

Investigators suggest that loss of oxygen in the global ocean is accelerating due to climate change and excess nutrients, but how sudden deoxygenation events affect tropical marine ecosystems is poorly understood. Past research shows that rising temperatures can lead to physical alterations in coral, such as bleaching, which occurs when corals are stressed and expel algae that live within their tissues. If conditions don’t improve, the bleached corals then die. However, the real-time changes caused by decreasing oxygen levels in the tropics have seldom been observed.

At a local scale, hypoxic events may pose a more severe threat to coral reefs than the warming events that cause mass bleaching. These sudden events impact all oxygen-requiring marine life and can kill reef ecosystems quickly.

Investigators reported coral bleaching and mass mortality due to this occurrence, causing a 50% loss of live coral, which did not show signs of recovery until a year after the event, and a drastic shift in the seafloor community. The shallowest measurement with hypoxic waters was about 9 feet deep and about 30 feet from the Bocas del Toro shore.

What about the 50% of coral that survived? Johnson and her fellow investigators found that the coral community they observed in Bocas del Toro is dynamic, and some corals have the potential to withstand these conditions. This discovery sets the stage for future research to identify which coral genotypes or species have adapted to rapidly changing environments and the characteristics that help them thrive.

Investigators also observed that the microorganisms living in the reefs restored to a normal state within a month, as opposed to the macro-organisms, like the brittle stars, who perished in these conditions. By collecting sea water samples and analyzing microbial DNA, they were able to conclude that these microbes did not necessarily adjust to their environment, but rather were “waiting” for their time to shine in these low-oxygen conditions.

“The take home message here is that you have a community of microbes; it has a particular composition and plugs along, then suddenly, all of the oxygen is removed and you get a replacement of community members. They flourish for a while, and eventually hypoxia goes away, oxygen comes back, and that community rapidly shifts back to what it was before due to the change in resources. This is very much in contrast to what you see with macro-organisms,” said Jarrod Scott, paper co-author and postdoctoral fellow at the Smithsonian Tropical Research Institute in the Republic of Panama.

Scott and Johnson agree that human activity can contribute to the nutrient pollution and warming waters which then lead to hypoxic ocean conditions. Activities such as coastal land development and farming can be better managed and improved, which will reduce the likelihood of deoxygenation events occurring.

The study provides insight to the fate of microbe communities on a coral reef during an acute deoxygenation event. Reef microbes respond rapidly to changes in physicochemical conditions, providing reliable indications of both physical and biological processes in nature.

The shift the team detected from the hypoxic microbial community to a normal condition community after the event subsided suggests that the recovery route of reef microbes is independent and decoupled from the benthic macro-organisms. This may facilitate the restart of key microbial processes that influence the recovery of other aspects of the reef community.

Now, two University of Washington scientists have developed a statistical framework that incorporates key COVID-19 data — such as case counts and deaths due to COVID-19 — to model the true prevalence of this disease in the United States and individual states. Their approach, published the week of July 26 in the Proceedings of the National Academy of Sciences, projects that in the U.S. as many as 60% of COVID-19 cases went undetected as of March 7, 2021, the last date for which the dataset they employed is available.

This framework could help officials determine the true burden of disease in their region — both diagnosed and undiagnosed — and direct resources accordingly, said the researchers.

“There are all sorts of different data sources we can draw on to understand the COVID-19 pandemic — the number of hospitalizations in a state, or the number of tests that come back positive. But each source of data has its own flaws that would give a biased picture of what’s really going on,” said senior author Adrian Raftery, a UW professor of sociology and of statistics. “What we wanted to do is to develop a framework that corrects the flaws in multiple data sources and draws on their strengths to give us an idea of COVID-19’s prevalence in a region, a state or the country as a whole.”

Data sources can be biased in different ways. For example, one widely cited COVID-19 statistic is the proportion of test results in a region or state that come back positive. But since access to tests, and a willingness to be tested, vary by location, that figure alone cannot provide a clear picture of COVID-19’s prevalence, said Raftery.

Other statistical methods often try to correct the bias in one data source to model the true prevalence of disease in a region. For their approach, Raftery and lead author Nicholas Irons, a UW doctoral student in statistics, incorporated three factors: the number of confirmed COVID-19 cases, the number of deaths due to COVID-19 and the number of COVID-19 tests administered each day as reported by the COVID Tracking Project. In addition, they incorporated results from random COVID-19 testing of Indiana and Ohio residents as an “anchor” for their method.

The researchers used their framework to model COVID-19 prevalence in the U.S. and each of the states up through March 7, 2021. On that date, according to their framework, an estimated 19.7% of U.S. residents, or about 65 million people, had been infected. This indicates that the U.S. is unlikely to reach herd immunity without its ongoing vaccination campaign, Raftery and Irons said. In addition, the U.S. had an undercount factor of 2.3, the researchers found, which means that only about 1 in 2.3 COVID-19 cases were being confirmed through testing. Put another way, some 60% of cases were not counted at all.

This COVID-19 undercount rate also varied widely by state, and could have multiple causes, according to Irons.

“It can depend on the severity of the pandemic and the amount of testing in that state,” said Irons. “If you have a state with severe pandemic but limited testing, the undercount can be very high, and you’re missing the vast majority of infections that are occurring. Or, you could have a situation where testing is widespread and the pandemic is not as severe. There, the undercount rate would be lower.”

In addition, the undercount factor fluctuated by state or region as the pandemic progressed due to differences in access to medical care among regions, changes in the availability of tests and other factors, Raftery said.

With the true prevalence of COVID-19, Raftery and Irons calculated other useful figures for states, such as the infection fatality rate, which is the percentage of infected people who had succumbed to COVID-19, as well as the cumulative incidence, which is the percentage of a state’s population who have had COVID-19.

Ideally, regular random testing of individuals would show the level of infection in a state, region or even nationally, said Raftery. But in the COVID-19 pandemic, only Indiana and Ohio conducted random viral testing of residents, datasets that were critical in helping the researchers develop their framework. In the absence of widespread random testing, this new method could help officials assess the true burden of disease in this pandemic and the next one.

“We think this tool can make a difference by giving the people in charge a more accurate picture of how many people are infected, and what fraction of them are being missed by current testing and treatment efforts,” said Raftery.

The research was funded by the National Institutes of Health.

Whole genome and whole exome sequencing of germline DNA was offered to all 309 patients who enrolled in the study. Whole genome, whole exome and RNA sequencing of tumor DNA was carried out for the 253 patients for whom adequate tumor samples were available.

Overall, 86% of patients had at least one clinically significant variation in tumor or germline DNA. Those included variants related to diagnosis, prognosis, therapy or cancer predisposition. Researchers estimated that 1 in 5 patients had clinically relevant mutations that would have gone undetected using standard sequencing methods.

“Some of the most clinically relevant findings were only possible because the study combined whole genome sequencing with whole exome and RNA sequencing,” said Jinghui Zhang, Ph.D., St. Jude Department of Computational Biology chair and co-corresponding author of the study.

Every tumor is unique. Every patient is unique.

Comprehensive clinical sequencing that includes whole genome, whole exome and RNA sequencing is not widely available. But as the technology becomes less expensive and accessible to more patients, researchers said comprehensive sequencing will become an important addition to pediatric cancer care.

“We want to change the thinking in the field,” said David Wheeler, Ph.D., St. Jude Precision Genomics team director and a co-author of the study. “We showed the potential to use genomic data at the patient level. Even in common pediatric cancers, every tumor is unique, every patient is unique.

“This study showed the feasibility of identifying tumor vulnerabilities and learning to exploit them to improve patient care,” he said.

Tumor sequencing guided the change in treatment for 12 of the 78 study patients for whom standard of care was unsuccessful. In four of the 12 patients, the changes stabilized disease and extended patient lives. Another patient, one with acute myeloid leukemia, went into remission and was cured by blood stem cell transplantation.

“Through the comprehensive genomic testing in this study, we were able to clearly identify tumor variations that could be treated with targeted agents, opening doors for how oncologists manage their patients,” said co-corresponding author Kim Nichols, M.D., St. Jude Cancer Predisposition Division director.

Additional findings and details

Genomes for Kids enrolled patients between August 2015 and March 2017.

Eighteen percent of patients carried germline variations in one of 156 known, cancer-predisposition genes.

Almost two-thirds of the germline variations identified would not have been detected based on current screening guidelines.

Next steps

Genomes for Kids helped launch the hospital’s clinical genomics program, which has enrolled about 2,700 cancer patients to date.

Meanwhile, data generated through the Genomes for Kids study are available at no cost to the international research community. By sharing the data, St. Jude aims to speed advances in understanding and treatment of pediatric cancer. The data are available in St. Jude Cloud.

“Even the most treatable cancers are not curable in all patients. For example, relapse remains the leading cause of death for the most common childhood cancer, acute lymphoblastic leukemia,” Nichols said. “Being able to understand and predict which patients will respond to treatment and which won’t requires collecting comprehensive genomic data on all patients.”

The team has recently submitted a patent disclosure with the Texas A&M Engineering Experiment Station.

“We claim several novelties in technological design as well as biological capabilities that didn’t exist in prior organs-on-chips,” said Dr. Abhishek Jain, lead researcher and assistant professor in the Department of Biomedical Engineering.

Jain also has a joint appointment in the College of Medicine at Texas A&M.

Jain’s device — the ovarian tumor microenvironment-chip (OTME-Chip) — focuses on platelets, tiny blood cells that help the body form clots to stop bleeding. The microdevice, about the size of a USB, models the properties of a tumor in the lab. Researchers then can recreate events within platelets circulating in the blood as they approach the tumor and make it more potent and metastatic.

“We are creating a platform technology using the organ-on-a-chip approach where tumor biology can be advanced, and new drugs can be identified by recreating the platelet-tumor and platelet-tumor-drug interactions under the influence of flow, supporting blood vessels and the extracellular matrix,” Jain said.

Ovarian cancer is a particularly challenging one to monitor. Tumors generally form deep inside a patient’s tissue, and it can be difficult to obtain real-time information of the tumor’s properties and how it is interacting with blood cells. Also, ovarian tumors can quickly spread inside the body, making time another vital factor in mapping the disease’s progression.

The OTME-Chip builds on the current clinically observed understanding of how blood platelets move inside tumor tissue and what triggers them to spread outside the tumor. However, the actual mechanism behind this process remains mostly unknown, until now.

“For the first time, we identified a crucial interaction between platelets and the tumor via their surface proteins,” Jain said. “By applying high-resolution imaging, advanced cell and molecular readouts and RNA sequencing methods leveraging the OTME-Chip, we discovered the actual genetic signaling pathways behind the blood cell triggered metastasis of ovarian cancer and a new drug strategy to stop this process.”

Jain’s team in College Station for this research includes postdoctoral researcher Dr. Biswajit Saha and doctoral students Jim Tronolone and Tanmay Mathur. Their research involving the OTME-Chip was recently published in the journal Science Advances.

Jain said the OTME-Chip has several applications, both in observing how cancer cells interact differently with vascular and blood cells and testing novel ways to treat the disease that may complement chemotherapy and radiotherapy of tumors.

“This multimodal OTME-Chip is going to provide an ideal platform to the health care researchers to evaluate their anti-cancer, vascular and hematological drugs individually or in combination in an artificially created human-level tumor microenvironment,” Jain said.

Jain collaborates with Dr. Anil Sood, professor and vice chair for translational research in the Departments of Gynecologic Oncology and Cancer Biology at MD Anderson Cancer Center. The team also works with Dr. Gang Bao, a gene editing expert from Rice University.

“Sood is a leader in the ovarian cancer field,” Jain said. “He has been a fantastic collaborator and has provided us access to patient tissue and blood samples needed to validate the findings from our chip, which brings us very close to initiating new clinical trials.”

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Materials provided by Texas A&M University. Original written by Jennifer Reiley. Note: Content may be edited for style and length.