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What The Viewpoint Says: This article describes treatment initiatives being undertaken for novel coronavirus 2019 at an ophthalmology center in Singapore.

Authors: Ivan Seah Yu Jun, M.B.B.S., of  National University Hospital of Singapore, is the corresponding author.

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(doi:10.1001/jamaophthalmol.2020.1288)

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Combining 89Zr-labeled antibodies with total-body positron emission tomography (PET) has extended the utility of novel total-body PET scanners, providing suitable images up to 30 days after the initial injection. A new study, published in the March issue of the Journal of Nuclear Medicine, compared four different types of 89Zr-labeled antibodies in preclinical trials, noting excellent consistency for each radiotracer even at very late time points, as well as differences in antibody behavior that are critical to understanding future outcomes of total-body PET in humans.

Monoclonal antibodies--laboratory-developed proteins designed to recognize specific targets--have been used in medicine for decades to treat various diseases, such as cancer, rheumatoid arthritis, multiple sclerosis and cardiovascular disease. Many new engineered monoclonal antibodies have been developed with specific molecular functions in order to achieve a balance between potency and safety in patient treatment.

"The tissue biodistribution of these newly engineered antibodies must be measured in vivo over the course of weeks to select the most appropriate candidates for novel therapeutics and understand how to use them in humans to best effect," said Simon Williams, PhD, principal scientist, molecular imaging at Genentech, Inc. "In our study, we assessed the feasibility of using a novel total-body PET scanner to image 89Zr-labeled antibodies up to 30 days after injection, allowing for the measurement of tissue biodistribution over a long period of time."

Researchers prepared four types of 89Zr-labeled antibodies, each with a different chelator-linker, to be compared across 12 young rhesus monkeys (three animals for each chelator-linker combination). Each group of animals received an intravenous injection of one of the four 89Zr-labeled antibodies in the left arm, along with an additional mass dose of unlabeled antibodies in the right arm. The animals were imaged on the day of injection, as well as three, seven, 14, 21 and 30 days after the injection.

Excellent image quality was obtained on the initial total-body PET scans for all four types of 89Zr-labeled antibodies. Results from the 30-day scans showed image quality across the four antibody types sufficient to readily identify activity in the liver, kidneys and upper and lower limb joints. However, significant differences in uptake between the various chelator-linker combinations were noted in the late time point liver, bone, and in whole-body clearance. These differences were determined to be partly related to the stability of the radiolabeled compounds prior to injection.

"The results of this study have two key implications for the field of molecular imaging," said Simon R. Cherry, PhD, distinguished professor at the University of California, Davis. "First, and most obvious, is that the increase in sensitivity of total-body PET, when compared to conventional PET, enables radiotracers to be followed for a longer period of time thus extending the imaging window. Using 89Zr as the radiolabel, this allows the assessment of slow biological processes and the ability to determine the ultimate fate of agents introduced into the body over a one-month timeframe."

He continued, "Second, studies with 89Zr can be conducted with much lower injected doses of radioactivity. The late time point total-body imaging conducted in this study clearly demonstrates that acceptable quality imaging with 89Zr can be accomplished when there is as little as 1/100th of the activity remaining in the subject. This paves the way for broad and repeat use of 89Zr-radiolabeled tracers in patients with extremely low effective doses."

The authors of "Total-Body PET and Highly Stable Chelators Together Enable Meaningful 89Zr-Antibody PET Studies up to 30 Days After Injection" include Eric Berg, Department of Biomedical Engineering, University of California-Davis, Davis, California; Herman Gill, Jan Marik, Annie Ogasawara and Simon Williams, Department of Biomedical Imaging, Genentech Inc., South San Francisco, California; Guus van Dongen and Daniëlle Vugts, Department of Radiology and Nuclear Medicine, Amsterdam UMC, VU University, Amsterdam, The Netherlands; Simon R. Cherry, Department of Biomedical Engineering, University of California-Davis, Davis, California, and Department of Radiology, School of Medicine, University of California-Davis, Davis, California; and Alice F. Tarantal, Department of Pediatrics and Department of Cell Biology and Human Anatomy, School of Medicine, and California National Primate Research Center, University of California-Davis, Davis, California.

The intestinal microbiota, composed by the microorganisms that live in our intestines, can give us information about our health, since its composition may depend on factors such as the diet, the lifestyle or our pathologies. Moreover, knowing what specific bacteria are in our intestines could help to predict diseases like colon cancer. New advances in genome sequencing methods, and bioinformatics tools that allow us to analyze the data, have helped us to identify thousands of new microorganisms present in our intestines through the analysis of their genome.

A team of researchers from the Bellvitge Biomedical Research Institute (IDIBELL) and the Catalan Institute of Oncology (ICO) has carried out a pilot test in the analysis of the intestinal microbiota genome. In this study, they analyzed, by two different sequencing methods, colon biopsies and fecal samples from nine patients. The aim has been to implement sequencing techniques and bioinformatics analysis tools.

It is the first study of a project that aims to be much more extensive. The data obtained in this pilot test will serve as the basis for the design of the analysis method for the Colonbiome project. This wide project aims to find microbiota markers that can be used for the early detection of colon cancer. To do this, colon biopsies and fecal samples will be collected from healthy patients and patients in different stages of colorectal cancer. Then the microbiota's genome will be sequenced to identify differences between groups.

Data available to everyone

All the data obtained in this pilot study has been entered into the European Nucleotide Archive, a public and collaborative database, where all types of genomic sequences are shared for the benefit of the entire scientific community. In addition, all the results of this first pilot test have been published in the Scientific Data journal, also a public journal, where both the sequences and the bioinformatics analysis methods used are detailed.

This study not only aims to be useful for the future work of the group, but it also aims to be helpful for all research groups that are carrying out similar analyses or trying new bioinformatics tools, who have open access to all the results obtained in this study. In addition, the researchers assure that they will also make public all the details of the subsequent studies, to continue contributing to collaboration and progress in the field.

The two sequencing methods

Two sequencing methods were compared in the study: the 16s and the Shotgun. The first is focused on the sequence of a single gene of the microorganisms, while the second gives us the complete sequence of the entire genome. Although the sequencing of a single gene implicates less sensibility, it can be cheaper. Furthermore, sequencing a gene only present in the microbiota allows us to analyze biopsy samples without the interference of the human genome.
Additionally, the pilot test has shown that both techniques are consistent. Although complete sequencing is more sensitive and can distinguish more species of microorganisms, the results are not contradictory to single-gene sequencing.

Continuous glucose monitor (CGM) and continuous subcutaneous insulin infusion (CSII) devices are known to improve outcomes in patients with type 1 diabetes (T1D), yet African American and Hispanic patients face barriers to the use of these devices, according to results of a small single-center retrospective study. The results of the ENDO 2020 abstract will be published in the Journal of the Endocrine Society.

"We observed that the use of technology among Caucasians was higher than its use in other racial and ethnic groups, and the difference was statistically significant," said lead author Kamonkiat Wirunsawanya, M.D., an endocrinology fellow at Boston University Medical Center in Boston, Mass. "Our study included an adult population that is more racially diverse than seen in the currently available literature."

Wirunsawanya, Ivania Rizo, M.D., and Kathryn Fantasia, M.D., all of Boston University Medical Center, examined the odds of CGM and CSII device use in patients of different races. They reviewed the electronic medical records of 227 adult patients who had type 1 diabetes and were seen in the endocrinology clinic of one safety-net hospital between October 2016 and September 2017.

Overall, 43% of patients were Caucasian, 25% were African American, 15% Hispanic, 2% Asian, and 15% who identified as other. While 30% of all patients in the study used CGM, its use varied by race: 47% of Caucasians used CGM, compared with 14% of African Americans, 23% of Hispanics, 25% of Asians, and 0% who identified as other. While 26% of all patients in the study used CSII, 43% of Caucasians used CSII, compared with 10% of African Americans, 14% of Hispanics, 18% of those who identified as other, and 0% of Asians.

The mean hemoglobin A1c level--a measurement of average blood glucose levels over the course of two to three months--was better controlled in patients who used CGM or CSII devices than those who did not. A1c levels were 8.27 in patients who used CGM, CSII, or both devices, compared to 9.49 in those who used no technology.

Patients who had government health insurance--roughly half of the participants--had lower odds of using technology than those with private health insurance.

Patients in the African American and "other" groups had lower odds of using technology, and the results were statistically significant.

"Our findings were consistent with racial disparities found in youth with type 1 diabetes and in adults with type 2 diabetes," Wirunsawanya said. "Our results add to the current knowledge of disparities in access to healthcare."

"Given the known benefits of diabetes technology and racial disparities in its use, future exploration of barriers is required," he said. "We hope our findings will allow endocrinologists to design and implement effective strategies to increase the use of technology among minority patients with type 1 diabetes."

WASHINGTON--Obese females that ate a small amount of coconut oil daily, even as part of a high-fat diet, had decreased features of metabolic syndrome, a cluster of risk factors that raise the chances of developing diabetes, heart disease and stroke, an animal study finds. The study results were accepted for presentation at ENDO 2020, the Endocrine Society's annual meeting, and will be published in a special supplemental section of the Journal of the Endocrine Society.

"Our controlled experimental study suggests that coconut oil may not be bad for cardiometabolic health, contrary to what previous studies have concluded," said the study's lead investigator, Annie Newell-Fugate, D.V.M., Ph.D., an assistant professor at Texas A&M University in College Station, Texas.

Nearly 40% of U.S. adults meet the criteria for obesity, the Centers for Disease Control and Prevention reports. One in five Americans has metabolic syndrome, which is linked partly to obesity, according to the Endocrine Society's Hormone Health Network. Adding to the problem, Newell-Fugate said, is that the typical Western diet may contain 40% or more fat.

The researchers wanted to learn whether eating a small amount of coconut oil could improve metabolism, despite consumption of a Western-style diet in which 49% of daily calories came from fat. Their study used an animal model of reproductive-age women with obesity and metabolic syndrome: sexually mature, female mini-pigs fed a high-fat, high-fructose diet resembling a Western diet. For eight months, two groups of pigs ate this high-fat diet consisting of 4,500 calories a day, but the groups differed by the type of one saturated fat. One group's food included 5% animal lard, which Newell-Fugate said some U.S. regions and ethnic cultures commonly use for cooking. The other high-fat diet group received 5% nonorganic coconut oil instead of lard in their food. A third group of pigs ate a low-calorie, lean diet as a control.

Although both groups fed the high-fat diet became obese, the pigs that received coconut oil had lower cholesterol and blood glucose (sugar) levels compared with the pigs that ate the lard-supplemented diet, Newell-Fugate reported. Also, the coconut oil group had less evidence of fatty liver disease and less deep belly fat than the lard group.

"Our research suggests that coconut oil may be used with lifestyle modifications and anti-diabetic drugs to treat metabolic syndrome, at least in women with obesity," Newell-Fugate said. She added that they do not know if their findings also apply to men.

Coconut oil is available in many grocery stores and could substitute for other saturated fats in small quantities, she suggested. "Substituting one tablespoon of your saturated fat calories per day with coconut oil could result in an improvement in your cardiometabolic health," Newell-Fugate said.

WASHINGTON--People who are very out of shape when they begin a behavioral weight loss program lose less weight in the long term than those who are more fit, suggests a new study that was accepted for presentation at ENDO 2020, the Endocrine Society's annual meeting, and will be published in a special supplemental section of the Journal of the Endocrine Society.

"This research could help us improve the design of our weight loss programs and suggests that adults with very poor fitness may benefit from additional exercise support during a weight loss program to achieve higher levels of moderate-to-vigorous physical activity and improve long-term weight loss," said lead researcher Adnin Zaman, M.D., of the University of Colorado Anschutz Medical Campus in Aurora, Colo.

Researchers examined the relationship between a person's level of fitness at the beginning of the study and weight loss at the end of an 18-month behavioral weight loss program. The program combined a calorie-restricted diet, group-based behavioral support, and six months of supervised exercise. The study included 60 adults with obesity or overweight. Participants exercised under supervision for the first six months of the study. They progressed to 300 minutes a week of moderate-intensity exercise over the six-month supervised exercise phase. When they completed their supervised exercise, they were advised to continue exercising at the same target for the rest of the study on their own.

The participants wore an armband that measured their activity levels over one week at the beginning of the study, and then for a week during months 6, 12 and 18. Their cardiovascular fitness was measured during a graded exercise test on a motorized treadmill. Participants were divided into two groups: "very poor fitness" and "poor or better fitness." Twenty (33%) of the adults who completed the 18-month study were classified as having very poor fitness at the beginning of the study, while 40 (67%) were categorized as having poor or better fitness.

Body mass index--a measure of body fat based on height and weight--was higher in those with very poor fitness at the beginning of the study compared with those in the poor or better fitness group. There were no significant differences between the two groups in weight change at 6 or 12 months. At 18 months, however, those in the poor or better category lost nearly twice as much weight as those who had very poor fitness at the start of the study--an average of 18 pounds versus 9.5 pounds.

Those with very poor fitness weren't able to do as many bouts of moderate-to-vigorous physical activity for at least 10 minutes at a time at the start of the study compared to those in the poor or better fitness group. Both groups increased the amount of moderate-to-vigorous activity they were able to do over the course of the study, but the very poor fitness group was not able to do as much--an average of 24 minutes a day, compared with 42 minutes a day for the more fit group.

Zaman said that the results may be influenced by other factors linked to low fitness that they did not measure. "Future studies are needed to evaluate whether providing additional exercise support or focusing specifically on improving fitness in adults with low levels of fitness would improve weight loss," she said.

WASHINGTON--Bariatric surgery may be an effective treatment for non-alcoholic fatty liver disease (NAFLD), suggests a new study accepted for presentation at ENDO 2020, the Endocrine Society's annual meeting, and publication in the Journal of the Endocrine Society.

The study compared three types of bariatric, or weight loss, surgery: gastric sleeve, gastric band and gastric bypass. "We believe that gastric bypass may be the best surgical option in these patients," said lead researcher Marta Borges-Canha, Ph.D., of Centro Hospitalar Universitário de São João in Porto, Portugal.

NAFLD is a condition in which excess fat is stored in the liver. This buildup of fat is not caused by heavy alcohol use. NAFLD is one of the most common causes of liver disease in the United States. The condition usually doesn't cause symptoms and is most often found when blood tests indicate elevated liver enzymes.

NAFLD is more common in people who have certain conditions, including obesity and conditions that may be related to obesity, such as type 2 diabetes. Researchers have found NAFLD in 40% to 80% of people who have type 2 diabetes and in 30% to 90% of people who are obese.

When the fat builds up in the liver and causes inflammation and damage, it is known as non-alcoholic steatohepatitis (NASH), which can lead to scarring of the liver--a potentially life-threatening condition called cirrhosis.

"NAFLD is strongly associated with obesity, and the prevalence of both diseases is notably increasing," Borges-Canha said. "There is a concerning lack of effective treatment options for patients with NAFLD." No medicines have been approved to treat NAFLD. The current recommended treatment is weight loss, which can reduce fat in the liver, inflammation, and fibrosis, or scarring.

The new study evaluated the effects of bariatric surgery on liver function and indicators of liver inflammation and scarring. The researchers included 1,995 morbidly obese patients who underwent bariatric surgery between January 2010 and July 2018. Their average age was 43, and 85.8% were female. One year after surgery, the patients had a significant decrease in liver enzymes. Other indicators of fatty liver disease, including the Fatty Liver Index (FLI), markedly decreased after one year. FLI is an algorithm that predicts liver steatosis or fat deposition. It is based on waist circumference, body mass index and levels of triglyceride and an enzyme found in the liver called γ-glutamyltransferase.

Another measure of fatty liver disease, called the BARD score, also markedly decreased. The BARD score predicts liver scarring. It is calculated using the ratio of two liver enzymes, body mass index and the presence of diabetes.

Gastric sleeve was associated with a greater reduction of liver enzymes and both FLI and BARD compared with gastric band. However, gastric sleeve led to a smaller reduction of FLI and BARD compared with gastric bypass surgery.

WASHINGTON--Two newer types of medications commonly used to treat type 2 diabetes are similar in their ability to reduce major heart complications, including heart attack, stroke and death from cardiovascular disease, according to research accepted for presentation at ENDO 2020, the Endocrine Society's annual meeting, and publication in a special supplemental section of the Journal of the Endocrine Society.

One class of drugs, known as SGLT2 inhibitors, has a clear benefit over the other class, known as GLP-1 drugs, in reducing hospitalization for heart failure, the study found. "This helps doctors more easily choose a medicine to best treat diabetes," said lead study author Ali Al-Khazaali, M.D., of Saint Louis University in St. Louis, Mo.

SGLT2 inhibitors are prescription oral medications used to treat type 2 diabetes. They include canagliflozin (Invokana), dapagliflozin (Farxiga) and empagliflozin (Jardiance). The study compared these drugs with injected diabetes drugs known as GLP-1 receptor agonists. These include albiglutide (Tanzeum), dulaglutide (Trulicity), exenatide (Byetta), liraglutide (Victoza) and semaglutide (Ozempic).

In prior studies, it was found that these two classes of drugs showed heart and kidney benefits besides controlling the blood sugar.

The researchers analyzed data from six previous trials of GLP-1 (including a total of 51,762 subjects) and four trials of SLGT2 inhibitors (including 33,457 subjects). Both drug classes were equally effective in reducing combined major adverse cardiac events such as heart attack, stroke and death from cardiovascular disease, compared to people with diabetes who were not taking the drugs.

The rate of hospitalization for heart failure was 32% less in patients taking SLT2 inhibitors compared to patients not taking the drugs, especially in those with more severe cardiovascular disease risk. In contrast, people taking GLP-1 drugs did not have a reduced rate of hospitalization for heart failure compared with people who had diabetes but were not taking the drugs. Both classes of drugs demonstrated kidney benefit; neither class was superior.

The most common serious side effects for SGLT2 inhibitors included yeast infections in women and diabetic ketoacidosis, a rare life-threatening problem that can affect people with diabetes. The major serious side effect for GLP-1 drugs was stomach upset.

"Doctors need to balance this side effect against the possible weight-loss benefits of this medicine," Al-Khazaali said.

WASHINGTON--Exercising women who struggle to consume enough calories and have menstrual disorders can simply increase their food intake to recover their menstrual cycle, according to a study accepted for presentation at ENDO 2020, the Endocrine Society's annual meeting, and publication in the Journal of the Endocrine Society.

The study found that exercising women with menstrual disorders can start menstruating again by consuming an additional 300-400 calories a day.

"These findings can impact all exercising women, because many women strive to exercise for competitive and health-related reasons but may not be getting enough calories to support their exercise," said lead researcher Mary Jane De Souza, Ph.D., of Penn State University.

By consuming enough calories, exercising women with menstrual disorders can avoid complications associated with a condition known as the Female Athlete Triad, De Souza said. This is a medical condition that starts with inadequate food intake that fails to meet the body's needs. It leads to menstrual disorders and poor bone health. It is associated with a high incidence of stress fractures.

The study included 62 young, exercising women with infrequent menstrual periods. Thirty-two women increased their calorie intake an average of 300-400 calories a day, and 30 maintained their exercise and eating habits for the 12-month study. Women who consumed the extra calories were twice as likely to have their menstrual period during the study compared with the women who maintained their regular exercise and eating routine.

"This strategy is easy to implement with the help of a nutritionist. It does not require a prescription and avoids complications from drug therapy," De Souza said. "The findings will encourage healthcare providers to try to help exercising women with menstrual disorders who consume too few calories to eat more, and this may help them to be healthier athletes and avoid bone complications."

WASHINGTON--Adults with type 2 diabetes requiring insulin therapy can safely achieve good blood sugar control using regular human insulin (RHI) in a wearable, patch-like insulin delivery device called V-Go®, a new study finds. Results of the randomized controlled study--which was accepted for presentation at ENDO 2020, the Endocrine Society's annual meeting, and will be published in a special supplemental section of the Journal of the Endocrine Society--suggest "a more affordable option" for insulin therapy than newer insulin types, the researchers said.

"The modern insulins--rapid acting insulin (RAI) analogs--have dominated the mealtime insulin market for years, but skyrocketing prices have resulted in concerns of affordability and whether their differences from other available insulins are clinically relevant," said study lead investigator Pablo Mora, M.D., an endocrinologist at Dallas Diabetes Research Center at Medical City, Dallas, Texas.

When injected by an insulin pen or insulin syringe, RHI--an older and less expensive insulin--takes longer to reach the bloodstream and has a longer duration of action compared to modern RAIs, Mora said. These differences can influence blood glucose control, he noted.

V-Go is a 24-hour small, disposable mechanical device that, according to its manufacturer, Valeritas, Inc., is cleared for use with RAI in adults with diabetes, is easy to use and worn like a patch on the skin. It has the ability to deliver both a steady continuous subcutaneous infusion of insulin for 24 hours and mealtime insulin dosing on demand, Mora said.

The study was conducted at three study centers in the southern United States and evaluated the safety and effectiveness of delivering RHI with V-Go in 113 adults with type 2 diabetes who were currently using the device filled with RAI. The investigators randomly assigned 54 patients to continue using the V-Go with RAI, and they assigned another 59 patients to switch the insulin used to fill V-Go from RAI to RHI. Over the 14-week study, which Valeritas, Inc. supported with an educational grant, the researchers measured the between group difference in average change in hemoglobin A1c, a measure of long-term blood glucose control.

The research team reported that improvements in A1c were observed, with a decrease of 0.6% in the RHI group and a decrease of 0.38% in the RAI group. Mora also stated that the study met its primary endpoint of noninferiority, or similar blood glucose control. The researchers found no between-group differences in the total daily dose of insulin required or in episodes of low blood sugar, a measure of safety.

"By continuously infusing insulin for 24 hours with V-Go, differences in duration of insulin action are minimized between the two insulins. Our results support that RHI can be safely and effectively used when delivered by V-Go", Mora said, who reported receiving consulting and speaking fees from Valeritas, Inc.: "Use of RHI with V-Go expands the affordability of insulin therapy."

WASHINGTON--Researchers and clinicians have been trying to find a way to diagnose nonalcoholic steatohepatitis (NASH) without taking a liver tissue biopsy, but according to new research, formulas that aim to predict NASH based on risk factors do not agree with each other and their accuracy varies. The study was accepted for presentation at ENDO 2020, the Endocrine Society's annual meeting, and publication in a special supplemental section of the Journal of the Endocrine Society.

"The three non-invasive methods we investigated agreed on a NASH diagnosis for only about one-fifth of the participants in the database," said lead study author Theodore C. Friedman, M.D., Ph.D., chair of the Department of Internal Medicine of Charles R. Drew University of Medicine and Science in Los Angeles, Calif. "These results imply that better methods are needed to predict NASH."

NASH is a serious condition that occurs when fat accumulates in the liver, causing inflammation and damage that can lead to cirrhosis and hepatic cancer. Liver biopsy is currently the best way to diagnose NASH, but this minor surgery can be expensive and carries some risk.

The research team analyzed data from 13,910 participants between 20 and 74 years of age who participated in the National Health and Nutrition Examination Survey III (NHANES III) between 1988 and 1994 and who underwent liver ultrasound. The authors excluded those with severe alcohol intake and identified those who had fat in the liver, which could be an indication of NASH.

Using variables available in NHANES III, they compared three of the non-invasive methods that use a different set of potential risk factors to predict the likelihood of a person having NASH: the HAIR score, the NASH liver fat score, and the Gholam score. The HAIR score is based on hypertension, alanine transaminase (ALT) levels, and insulin resistance. The NASH liver fat score incorporates metabolic syndrome, type 2 diabetes, serum insulin, ALT and aspartate aminotransferase (AST). The Gholam score uses AST and type 2 diabetes diagnosis.

All three methods agreed on a NASH diagnosis in only about one-fifth of the study participants. Of the 1,236 individuals who were determined by at least one method to have NASH, 18 percent were identified by all three methods, while 20 percent were identified by two.

All three methods identified significant risk factors for NASH as being overweight or obese, having elevated AST or ALT, and having elevated C-peptide, serum glucose, or serum triglycerides. According to the HAIR and Gholam methods, but not the NASH liver fat score, being Mexican-American was a significant risk factor, while the NASH liver fat score found that being a former alcohol drinker and not meeting physical activity guidelines carried significant risk.

"Because the results differ depending which method is used, considerable care must be taken in interpreting the risk factors," Friedman cautioned. "In clinical practice, patients and their risk factors may be misidentified if formulas, not liver biopsies, are used."

"More work needs to be done to find a valid and reliable non-invasive way to diagnose NASH that avoids the costs and risks of liver biopsy," he noted, adding, "NHANES will be releasing new data on using a different type of liver ultrasound that may be helpful in predicting NASH."

WASHINGTON--Men with erectile dysfunction have a higher risk of death, regardless of their testosterone levels, suggests a study accepted for presentation at ENDO 2020, the Endocrine Society's annual meeting, and publication in a special supplemental section of the Journal of the Endocrine Society.

"As both vascular disease and low testosterone levels can influence erectile function, sexual symptoms can be an early sign for increased cardiovascular risk and mortality," said lead researcher Leen Antonio, M.D., Ph.D., of KU Leuven-University Hospitals in Belgium.

Low testosterone levels have been linked to a higher risk of death in middle-aged and older men, but results from large studies are inconsistent, Antonio said. Studies have also linked sexual dysfunction with mortality in older men.

The new study used data from the European Male Ageing Study (EMAS), a large observational study that was designed to investigate age-related hormonal changes and a broad range of health outcomes in elderly men. The researchers analyzed data from 1,913 participants in five medical centers. They analyzed the relationship between their hormone measurements and sexual function at the beginning of the study, and whether they were still alive more than 12 years later.

During the average follow-up period of 12.4 years, 483 men--25 percent--died. In men with normal total testosterone levels, the presence of sexual symptoms, particularly erectile dysfunction, increased the risk of death by 51 percent compared with men without these symptoms.

Men with low total testosterone levels and sexual symptoms had a higher risk of death compared with men with normal testosterone levels and no sexual symptoms.

Men with erectile dysfunction, poor morning erections and low libido had a higher mortality risk compared to men with no sexual symptoms. In men with these three sexual symptoms, the risk of dying was almost 1.8 times higher compared to men without symptoms. In men with just erectile dysfunction, the risk of dying was 1.4 times higher compared to men without erectile dysfunction.

Levels of free testosterone (the testosterone that is easily used by the body) were lower in those who died. Men who had the lowest levels of free testosterone had a higher risk of death compared to men who had the highest levels.

We all learnt in school that the beams from x-ray machines pass right through soft tissues like skin and internal organs, but not dense materials like bones, right? Not so fast.

Researchers in Japan have figured out a way to use x-rays to tell doctors about those squishy parts as well, not just bones, in a similar way to how ultrasound or magnetic resonance imaging (MRI) work--but with much greater resolution.

This greater resolution for the field of elastography--a non-invasive method of medical imaging that investigates the stiffness and elasticity of soft tissue--should allow healthcare professionals to identify much smaller and deeper tissue problems, such as lesions, than they can with ultrasound or MRI, the two main types of elastography used currently. The scientists published their results in March in the journal Applied Physics Express.

Although previous studies have suggested such x-ray elastography is possible in principle, this is the first time that any real-world visualization of stiffness using the concept has been demonstrated.

Ultrasound uses sound waves with frequencies higher than what humans can hear, and works by sending "shear waves" through us--the sort of waves that occur when you whip a rope up and down quickly. Shear waves travel faster through stiffer tissue than through softer tissue. Since cancerous tumors, lesions from cirrhosis of the liver and hardened arteries are stiffer than the surrounding healthy tissue, identifying where the waves pass through tissue more slowly, clinicians are able to spot these stiffer tissues.

MRI works in a related fashion, but via the use of very strong magnets to force protons in the body to align with a magnetic field. How long it takes those protons to make this move tells us a similar story about stiff or hard tissues.

Now, researchers have developed a technique to do much the same with x-rays instead. The advantage? X-rays can provide much greater resolution than ultrasound--on the order of tens of micrometers (millionths of a meter) instead of millimeters (mere thousandths of a meter).

"This greater precision doesn't just mean identification of much smaller or deeper lesions," said lead researcher Wataru Yashiro, an associate professor from the Institute of Multidisciplinary Research for Advanced Materials (IMRAM) of Tohoku University, "but, importantly for patients, because smaller lesions can be newer ones, potentially also much earlier on in a disease or condition."

The next step is to further develop the technique to produce 3D visualizations, and ultimately the researchers want to manufacture x-ray elastography medical diagnostic equipment.

Philadelphia, March 31, 2020 - Researchers in Korea have developed a deep learning-based artificial intelligence (AI) algorithm that can accurately classify cutaneous skin disorders, predict malignancy, suggest primary treatment options, and serve as an ancillary tool to enhance the diagnostic accuracy of clinicians. With the assistance of this system, the diagnostic accuracy of dermatologists as well as the general public was significantly improved. This novel study is reported in the Journal of Investigative Dermatology.

Skin diseases are common, but it is not always easy to visit a dermatologist quickly or distinguish malignant from benign conditions. "Recently, there have been remarkable advances in the use of AI in medicine. For specific problems, such as distinguishing between melanoma and nevi, AI has shown results comparable to those of human dermatologists. However, for these systems to be practically useful, their performance needs to be tested in an environment similar to real practice, which requires not only classifying malignant versus benign lesion, but also distinguishing skin cancer from numerous other skin disorders including inflammatory and infectious conditions," explained lead investigator Jung-Im Na, MD, PhD, Department of Dermatology, Seoul National University, Seoul, Korea.

Using a "convolutional neural network," a specialized AI algorithm, investigators developed an AI system capable of predicting malignancy, suggesting treatment options, and classifying skin disorders. Investigators collected 220,000 images of Asians and Caucasians with 174 skin diseases and trained neural networks to interpret those images. They found that the algorithm could diagnose 134 skin disorders and suggest primary treatment options, render multi-class classification among disorders, and enhance the performance of medical professionals through Augmented Intelligence. Most prior studies have been limited to specific binary tasks, such as differentiating melanoma from nevi.

The algorithm's performance was initially compared with the performance of 21 dermatologists, 26 dermatology residents, and 23 members of the general public. Its performance was similar to that of the dermatology residents but slightly below that of the dermatologists. After the initial test, the test participants were informed of the results of the algorithm and subsequently modified their answers. The sensitivity of the malignancy diagnosis of the 47 clinicians improved from 77.4 percent to 86.8 percent. Similarly, the sensitivity of the diagnosis of malignancy by the 23 members of the general public improved markedly from 47.6 percent to 87.5 percent. Notably, based on the initial result, half of the malignancies would have been missed by the general public without referral to specialists.

"Our results suggest that our algorithm may serve as an Augmented Intelligence that can empower medical professionals in diagnostic dermatology," noted Dr. Na. "Rather than AI replacing humans, we expect AI to support humans as Augmented Intelligence to reach diagnoses faster and more accurately."

The researchers caution that AI cannot definitively interpret images that it is not trained to interpret even when the problem presented is straightforward. For example, an algorithm trained only to differentiate between melanoma and nevi cannot differentiate between an image of a nail hematoma and either a melanoma or a nevus. If the shape of the hematoma is irregular, the algorithm may diagnose it as melanoma. They also point out that the algorithm was trained and tested using high quality images and its performance is generally suboptimal if the input images are of low quality.

In addition, a diagnosis made with only one image with the most optimal composition may present inherent limitations compared to diagnoses made in a clinical setting. In a real practice, a dermatological diagnosis is made based on the combination of multiple sources of information including past medical history, symptoms, appearance compared to other lesions on the patient and the texture of the lesion assessed by physical contact.

"We anticipate that the use of our algorithm with a smartphone could encourage the public to visit specialists for cancerous lesions such as melanoma that might have been neglected otherwise," commented Dr. Na. "However, there are issues with the quality or composition of photographs taken by the general public that may affect the results of the algorithm. If the algorithm's performance can be reproduced in the clinical setting, it will be promising for the early detection of skin cancer with a smartphone. We hope that future studies will evaluate the utility and performance of our algorithms in a clinical setting."

An early demo version of the team's deep learning approach is available via its website. By analyzing data through the website, the researchers hope to identify possible problems that could still arise if the AI were used via telemedicine, which relies more heavily upon clinical photography to diagnose skin disorders.However, such diagnoses will still need to be verified by dermatologists along with the patient's medical history and physical examination.

A new fennel fungal disease caused by a new genus and species - Ochraceocephala foeniculi, was observed for the first time in 2017 on 5% of the "Apollo" fennel cultivar grown in the sampled localities in Catania province, Italy. Now, it has spread to 2 more cultivars: "Narciso" and "Pompeo", causing crop losses of around 20-30%. The new pathogen damages the fennel with necrotic lesions on the crown, root and stem.

Fennel, a crop native in arid and semi-arid regions of southern Europe and the Mediterranean area is massively used as a vegetable, herb and seed spice in food, pharmaceutical, cosmetic and healthcare industries with Italy taking the world-leading production. It is an important and widely cultivated crop in Sicily (southern Italy).

Worldwide, fennel crops are affected by several fungal diseases. In Italy, amongst soilborne diseases, there have been reports of brown rot and wilt caused by Phytophthora megasperma and crown rot caused by Didymella glomerata.

International research group, led by Ms. Dalia Aiello from the University of Catania, made the first step in handling the new fennel disease by identifying the causal agent obtained from symptomatic plants and publishing the results of their research in the open-access journal Mycokeys.

In order to understand the origin of the causal agent, scientists collected 30 samples during several surveys in the affected areas in Sicily, and studied the consistently grown fungal colonies from symptomatic tissues.

"The fungal species obtained from symptomatic tissues was identified based on morphological characters and molecular phylogenetic analyses of an ITS-LSU-SSU rDNA matrix, resulting in the description of the fennel pathogen as a new genus and species, Ochraceocephala foeniculi," shares Dr. Dalia Aiello.

According to the pathogenicity tests, O. foeniculi causes symptoms on artificially inoculated plants of the same cultivar. Preliminary evaluation of fennel germplasm, according to the susceptibility to the new disease, shows that some cultivars ("Narciso", "Apollo" and "Pompeo") are more susceptible and some are less susceptible ("Aurelio", "Archimede" and "Pegaso"), but this is a subject yet to be confirmed by additional investigations. More studies are required in order to plan further effective disease management strategies.

"On the basis of the disease incidence and severity observed in the field, we believe that this disease represents a serious threat to fennel crop in Sicily and may become a major problem also to other areas of fennel production if accidentally introduced," concludes Dr. Dalia Aiello.