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Tuesday, April 2, 2019

Deferred umbilical cord clamping could save many premature infants

New research shows delayed umbilical cord clamping improves survival and reduces risk of brain injury in extremely premature infants.
A baby’s is typically clamped and cut immediately after birth. Over the years, emerging research has suggested there may be benefits to delaying umbilical cord clamping in term neonates. However it was not clear if this intervention would also have benefits on the survival of extremely low gestational age preterm neonates.
In a new study published in JAMA Network Open, neonatologist Dr. Abhay Lodha, MD, and his research team found for the first time that delaying umbilical cord clamping in extremely preterm babies improves their survival. It also lowers the odds of severe neurological injury in the form of an intraventricular hemorrhage, or bleeding in the brain.
“Delaying cord clamping allows time for the baby’s  to stabilize,” says Lodha, associate professor in the departments of Paediatrics and Community Health Sciences at the Cumming School of Medicine and a member of the Alberta Children’s Hospital Research Institute. “As premature babies’ brain vessels are quite fragile, a rapid change in blood pressure can rupture their blood vessels, causing a brain hemorrhage.”
In this , researchers analyzed the outcomes of 4,680 neonates across Canada who were born at 22 to 28 weeks and were admitted to a neonatal intensive care units (NICU). The study suggests deferred umbilical cord clamping (DCC) leads to circulatory stability, which improves blood pressure and reduces the need for transfusions.
The researchers also found DCC reduced the risk of infection by allowing the newborn to receive more nutrient- and immune cell-rich  from the mother.
“As long as the baby is stable at the time of birth, we recommend delaying umbilical cord clamping for 30 to 60 seconds,” says Lodha. “This is a simple intervention that could reduce the need for medication to treat hypotension, reduce the risk of infections, and improves the baby’s survival. We hope this new information will have a global impact, especially in developing countries, and save many premature neonates.”
Going forward, the research team plans to study the long term neurodevelopmental outcomes of preterm neonates who received DCC at birth.

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More information: Abhay Lodha et al. Association of Deferred vs Immediate Cord Clamping With Severe Neurological Injury and Survival in Extremely Low-Gestational-Age Neonates, JAMA Network Open (2019). DOI: 10.1001/jamanetworkopen.2019.1286

New thermal ablation method for adenoma shows promise

Researchers from the USA (Kansas State University) and the Republic of Ireland (the National University of Ireland Galway) have completed a successful initial test of a new microwave thermal ablation technique, which could eventually be used to treat Conn’s syndrome.
Conn’s syndrome occurs when a benign adrenal gland adenoma causes the production of excess aldosterone, which leads to high blood pressure. Treatment for the condition is currently limited to two options: an adrenalectomy or intensive medical management with significant side effects.
The researchers’ new technique, explained in Biomedical Physics and Engineering Express, could ultimately lead to a non-invasive treatment of small adenomas of up to 20 mm in size, without damaging surrounding tissue.
Hojjatollah Fallahi from Kansas State University, USA, is the study’s lead author. He said: “Microwave Ablation (MWA) is a form of thermal  most often used to treat cancer. It uses  in the microwave energy spectrum (300 MHz to 300 GHz) to heat tissue.
“However, tumour ablation devices and systems were developed to treat large tumours, by maximizing the size of the ablation zone. We wanted to overcome the challenge for adrenal ablation, where the objective is to treat small adenomas while minimizing thermal damage to non-targeted adrenal tissue and preserving adrenal function.”
The international team suspected that water-cooled monopole antennae, operating at 2.45GHz and 5.8GHz, would allow the creation of short, round ablation zones from 10 to 20 mm in diameter.
To test this theory, they used a combination of computer modelling and ex vivo experiments with cow liver and adrenal gland tissue to investigate the ability to control ablation zone size, by adjusting antenna operating frequency, applied power, ablation duration, and coolant temperature.
Mr Fallahi said: “We found that small spherical ablation zones with diameters in the range of 7.4 – 17.6 mm can be obtained by adjusting the applied power and ablation duration. An analysis of the experimentally-measured ablation zone dimensions showed that frequency of operation and ablation duration are the main parameters for controlling the ablation zone length and width, respectively.
“We also discovered that the coolant temperature provides another effective parameter for controlling the ablation zone length, without affecting the ablation zone width.
“Our results demonstrate the feasibility of creating small spherical  zones, suitable for targeting benign adrenal adenomas. Further work is now needed to examine the applications of the technique in more depth and establish if it is suitable for use in human patients with Conn’s syndrome.”

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More information: Hojjatollah Fallahi et al. Microwave antennas for thermal ablation of benign adrenal adenomas, Biomedical Physics & Engineering Express (2019). DOI: 10.1088/2057-1976/ab068b

Come for fillings, stay for fillers: Some dentists offer Botox, cosmetic treatments

After a plastic surgeon’s office botched her dermal fillers, Tima Barkeshli found a different destination for cosmetic treatments: her dentist’s office.
From his suite in Columbia, Md., Dr. Javod Gol is among the ranks of dentists who are increasingly treating not only the teeth, but everything that frames them. In addition to teeth-cleanings, crowns and cavity fillings, he offers patients like Barkeshli Botox, dermal fillers and small sutures that lift and tighten their skin.
“It rejuvenates your face, which is what I’m looking for,” Barkeshli, a 33-year-old Bethesda, Md., resident, said of the Botox and fillers she’s received from Gol. “I’m not looking to look different. I’m not even looking to look so much younger. It’s more like I want to look fresh and rejuvenated.”
For more than a decade, regulatory boards have authorized the use of botulinum toxin—known under the popular brand name Botox—and other non-surgical cosmetic procedures by dentists. In addition to its cosmetic applications, Botox can be used to treat temporomandibular joint disorders—which cause pain where the jaw and cheek bones meet—as well as conditions like migraines and teeth grinding.
“This was pretty much a natural extension as more and more regulatory dental boards accepted the use of Botox and fillers as the standard of practice in dentistry,” said Dr. Louis Malcmacher, president of the American Academy of Facial Esthetics, which trains dentists and other health care professionals in applying the treatments. “More and more dentists are adopting the use of them every single day.”
With three levels of certification from the American Academy of Facial Esthetics, Gol’s cosmetic work ranges from procedures as simple as injecting Botox to smooth fine lines on the forehead, to the more complex “Nefertiti lift,” which tightens skin along the neck and jawline.
Dentists’ familiarity with facial anatomy makes them reliable providers for facial injections, Malcmacher said, adding they also understand how to treat complications that could arise.
“The face is where dentists live most of their professional life,” Malcmacher said. “Dentists for years have been certainly taking care of teeth but certainly have been involved in all the soft tissues around the mouth.”
Though the smile is the focus of dentists’ work, Gol said he likes to think beyond patients’ teeth.
“If you spend 10(,000) or 20,000 dollars on your teeth, it’s like a perfect piece of artwork, OK,” Gol said. “You’re not going to go and get a piece of artwork and put it in a $10 frame; you want it framed properly.”
Facial cosmetic work is not a fit for every practice, said Dr. Charles Doring, an instructor at the University of Maryland School of Dentistry. His family practice, North Bethesda Dental Associates, for example, treats patients ranging from young children to centenarians. Cosmetic facial treatments are not something his clients are asking for.
“For me it’s just not something I want to offer,” Doring said. “There’s a place for it, but it doesn’t fit into my practice M.O.”
Malcmacher estimated 18 to 20 percent of dentists have been trained in these procedures.
But about 10 percent of Gol’s dental patients seek Botox, fillers and other non-dental cosmetic treatments, he said. The most common Botox injection sites for his patients are the forehead, “crows feet” on the outsides of the eyes, and the “elevens,” or the glabellar complex between the eyebrows. With fillers, he often injects the lips (thanks, Kardashians), nasolabial folds (also known as laugh lines) and cheeks.
Botox treatments range from about $200-$600, while fillers cost about $500-$700 per syringe. Insurance does not typically cover cosmetic procedures.
Gol said he typically treats dynamic wrinkles with Botox first, to relax the muscles that cause lines on the skin. He then follows by treating static wrinkles with fillers, which help plump areas where people lose fat as they age.
“I would rather give you something that fits your face as opposed to giving something that everybody else gets,” Gol said. “What our body should take is different, so it really needs to be customized to you.”
He also tries to accentuate patient’s natural features, he said.
“Somebody who is like 45—they shouldn’t be getting fillers to look like they’re 25. When you’re 45 you can still look beautiful at 45, so let’s make you look like a beautiful 45-year-old,” Gol said. “What you want maybe isn’t the best for you.”
Such conversations with patients help determine their best course of treatment.
“That kind of patient-doctor relationship is very special in dentistry,” Malcmacher said. “And where that really comes in on the clinical side is I know my patient’s face, I’ve dealt with them for years.”
Baltimore resident Shane Gabriszeski said he’d been seeing Gol for about three years for his dental needs. He more recently began seeing him for Botox.
“One day in his office he asked me if I’d ever considered Botox for a wrinkle in my forehead that’s been there since I was a teenager,” he said. “It’s always bothered me but never enough to do anything about it.”
He tried it for the first time about 18 months ago, and goes back about every four months for injections. And Gol recently placed a PDO thread—a tiny suture that lifts the skin, dissolves and builds collagen—to give his skin a stronger lift.
“A lot of people might be hesitant to go to a dentist, but he is really good,” Gabriszeski, 33, said.
When Barkeshli found out Botox was an option at Gol’s office, she said she was glad to receive the treatments from a doctor she already trusted. She, too, was a dental patient first.
“The person who does it does matter, and I think it’s more experience than anything else,” she said. “He’s super easy on my teeth, so I like that, and then the same with the fillers.”
The results keep patients coming back, Gol said.
“Patients are a lot happier getting this than they are getting their dental work” Gol said. “Positive reinforcement has been the biggest thing for it—the fact that it’s something that makes people feel good and makes you want to do it again.”

New approach to repairing damaged peripheral nervous system

A new University of Virginia study proves that a damaged peripheral nervous system is capable of repairing itself—when healthy cells are recruited there from the central nervous system. The finding has implications for the future treatment of debilitating and life-threatening nervous system disorders affecting children, such as muscular dystrophy, Guillain-Barre Syndrome and Charcot-Marie-Tooth Disease.
The study will be published in the April 2 issue of the journal Cell Reports.
Researchers found that when they chemically disrupt specific mechanisms of neural activity in the , they can, in effect, open a border wall to allow a critical nerve-repairing cell to migrate into the peripheral nervous system—a region those cells generally don’t enter. The cells, a subset of non-neuronal cells called oligodendrocytes, ultimately come to function in their new environment, the muscles, in the same way they operate in their original home in the central nervous system—they make repairs to damaged .
Oligodendrocytes are a type of cell called glia. They are the glue that hold together brain matter, and are key components in the development of the central nervous system. These cells also are important to the regeneration or repair of these systems in response to disease or injury.
They make myelin, a layer of protein and fatty material that acts like electrical tape to insulate axons, a threadlike part of nerve cells on which  transmit in a line from one cell to the next. When that sheathing degenerates, such as happens to diseased nerve  in multiple sclerosis, critical messages from the brain are disrupted along the path to other areas of the body, resulting in severe impairment.
Study identifies new approach to repairing damaged peripheral nervous system
Sarah Kucenas, a UVA professor of biology, cell biology and neuroscience, and member of the UVA Brain Institute, led the study. Credit: University of Virginia
“Oligodendrocytes are highly migratory, but they always end up in the same locations of the central nervous system, even though they actually have the capability to go anywhere,” said study leader Sarah Kucenas, a UVA professor of biology, cell biology and neuroscience, and member of the UVA Brain Institute. “We set out to find the mechanism that might keep them restricted, and we found it.”
Using zebrafish as a study model (about 80 percent of a zebrafish’s nervous-system genes are the same as in humans), Kucenas and postdoctoral fellow Laura Fontenas discovered that oligodendrocytes are actively segregated to the central nervous system through tight control of neural activity. But they don’t necessarily have to be.
“When we disrupt specific mechanisms of neural activity, we find that we can actually get these oligodendrocytes to migrate to portions of the nervous system where they technically shouldn’t go—to the periphery—and we wanted to know if they can conduct repairs there,” Kucenas said.
She and Fontenas identified a compound that perturbs the oligodendrocytes into migration and used zebrafish that were genetically mutated to model such diseases as , Guillain-Barre syndrome and Charcot-Marie-Tooth disease. They disrupted the mechanism of neuronal activity to recruit oligodendrocytes to the peripheral nervous system, and found that they indeed replace defective myelin that is lost in those disorders.
In ongoing studies in the lab using models of these diseases, Kucenas and Fontenas are finding that adult fish with oligodendrocytes in the peripheral nervous system swim better than mutant adult fish with no oligodendrocytes. This suggests that a new class of drugs could be developed to coax oligodendrocytes to migrate to the and help it repair itself.
“This finding has a very real potential to change how we think about approaching the treatment of neurodegenerative diseases,” Kucenas said. “My hope is that someday our discoveries will help children with impairing neurological diseases to be able to get out of their wheelchairs and live an enhanced quality of life.”

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More information: Cell Reports (2019). DOI: 10.1016/j.celrep.2019.03.013

Transplanted marrow endothelial progenitor cells delay ALS progression

Transplantation of human bone marrow-derived endothelial progenitor cells (EPCs) into mice mimicking symptoms of amyotrophic lateral sclerosis (ALS) helped more motor neurons survive and slowed disease progression by repairing damage to the blood-spinal cord barrier (BSCB), University of South Florida researchers report.
The new study, published March 27 in Scientific Reports, contributes to a growing body of work exploring cell therapy approaches to barrier repair in ALS and other neurodegenerative diseases.
The progressive degeneration of nerve  that control muscle movement () eventually leads to total paralysis and death from ALS. Each day, an average of 15 Americans are diagnosed with the disease, according to the ALS Association.
Damage to the barrier between the blood circulatory system and the central nervous system has been recognized as a key factor in the development of ALS. A breach in this protective wall opens the brain and spinal cord to immune/ and other potentially harmful substances circulating in peripheral blood. The cascade of biochemical events leading to ALS includes alterations of endothelial cells lining the inner surface of tiny blood vessels near damaged spinal cord motor neurons.
This latest study by lead author Svitlana Garbuzova-Davis, Ph.D., and colleagues at the USF Health Morsani College of Medicine’s Center of Excellence for Aging & Brain Repair, builds upon a previous study showing that human bone marrow-derived  improved motor functions and nervous system conditions in symptomatic ALS mice by advancing barrier repair. However, in that earlier USF study the  was delayed until several weeks after cell transplant and some severely damaged capillaries were detected even after a high-dose treatment. So in this study, the researchers tested whether human EPCs—cells harvested from bone marrow but more genetically similar to vascular endothelial cells than undifferentiated stem cells—would provide even better BSCB restoration.
ALS mice were intravenously administered a dose of human bone-marrow derived EPCs. Four weeks after transplant, the results of the active cell treatment was compared against findings from two other groups of mice: ALS mice receiving a media (saline) treatment and untreated healthy mice.
The symptomatic ALS mice receiving EPC treatments demonstrated significantly improved motor function, increased motor neuron survival and slower  than their symptomatic counterparts injected with media. The researchers suggest that these benefits leading to BSCB repair may have been promoted by widespread attachment of EPCs to capillaries in the spinal cord. To support this proposal, they point to evidence of substantially restored capillaries, less capillary leakage, and re-establishment of structural support cells (perivascular astrocytes) that play a role in helping form a protective barrier in the  and brain.
Further research is needed to clearly define the mechanisms of EPC barrier repair. But, the study authors conclude: “From a translational viewpoint, the initiation of cell treatment at the symptomatic disease stage offered robust restoration of BSCB integrity and shows promise as a future clinical therapy for ALS.”

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More information: Svitlana Garbuzova-Davis et al, Human Bone Marrow Endothelial Progenitor Cell Transplantation into Symptomatic ALS Mice Delays Disease Progression and Increases Motor Neuron Survival by Repairing Blood-Spinal Cord Barrier, Scientific Reports (2019). DOI: 10.1038/s41598-019-41747-4

HHS website now lists ceiling prices for 340B drugs

A 340B facility can now determine whether it’s being bilked by a drug manufacturer for covered drugs thanks to an update to an HHS website.
The Health Resources and Services Administration on Monday updated the Office of Pharmacy Affairs 340B Information System, which facilities use to register for the program. It now allows 340B providers to verify the accuracy of ceiling prices drugmakers are charging.
The lobbying group 340B Health, which represents more than 1,300 hospitals, said the new information can also help increase accountability for drug manufacturers.
“When this information is combined with the civil monetary penalty authority that Congress granted HRSA, manufacturers that knowingly and intentionally charge safety-net providers too much will be subject to financial penalties,” 340B Health CEO Maureen Testoni said in a statement.
HRSA spokesman Martin Kramer told Modern Healthcare that the agency was required to update the website as a result of a long-delayed and controversial rule that went into effect in January.
HHS was originally supposed to finalize the rule in July 2018 and had wanted to delay the rule’s implementation until July 2019 because it was concerned whether the rule originally proposed by the Obama administration was legal.
However, the American Hospital Association and other hospital trade groups sued the agency last fall to get them to finalize the regulations. HHS eventually agreed to implement the rule and settled the lawsuit.
The lawsuit over the rule’s implementation has been one front in a war between hospital groups and the Trump administration on 340B.
The administration tried to make a roughly 30% cut to 340B reimbursements to facilities, but a federal judge struck down those cuts in December 2018, saying the agency didn’t have the authority to implement them.

Single-dose antidote may help prevent fentanyl overdoses

Synthetic opioids outlast current antidotes. A nanoparticle-based alternative could fix that.
A newly developed single-dose opioid antidote lasts several days, a study in mice shows. If the results can be duplicated in humans, the treatment may one day help prevent overdoses from deadly drugs like fentanyl.
Normally, a dose of the opioid antidote naloxone passes through a person’s body in about 30 minutes — far too quickly to fully counteract the effects of such synthetic opioids as fentanyl and carfentanil (SN Online: 5/1/18). These drugs, tens to thousands of times stronger than morphine, can linger in a person’s system for hours or even days (SN: 6/10/17, p. 22). That requires multiple doses of an antidote to prevent someone from overdosing.
So researchers developed a new naloxone-based antidote to outlast synthetic opioids by creating nanoparticles in which naloxone molecules are tangled up with a biodegradable polymer called polylactic acid. Water and enzymes in the body slowly break down these nanosized tangles, gradually releasing naloxone.
In mice, the new nanoparticle delivery system counteracted the pain-relieving effects of morphine for up to 96 hours after administering a single dose of the antidote, according to research being presented March 31 at the American Chemical Society meeting in Orlando, Fla.
“We’re now going to start moving onto fentanyl and carfentanil” and ramping up opioid doses to test whether the antidote can prevent a mouse from overdosing, says Saadyah Averick, a biomaterials researcher at the Allegheny Health Network Research Institute in Pittsburgh.
In 2017, synthetic narcotics like fentanyl far outstripped prescription opioids and heroin as the most common drugs involved in overdose deaths, according to the U.S. Centers for Disease Control and Prevention. Drugs specifically designed to counteract these synthetic opioids could play a key role in curbing these deaths.

Citations
S. Averick. Next-generation opioid antidotes: Covalent nanoparticles for the delivery of Mu opioid antagonists. American Chemical Society meeting, Orlando, Fla., March 31, 2019.

Further Reading
C. Vanchieri. U.S. fentanyl deaths are rising fastest among African Americans. Science News Online, March 22, 2019.
A. Cunningham. Drug overdoses in America are rising exponentially. Science News Online. September 20, 2018.
A. Cunningham. Synthetic opioids involved in more deaths than prescription opioids. Science News Online, May 1, 2018.
L. Sanders. Opioids kill. Here’s how an overdose shuts down your body. Science News Online, March 29, 2018.
L. Hamers. The opioid epidemic spurs a search for new, safer painkillersScience News. Vol. 191 No. 11, June 10, 2017, p. 22.
L. Sanders. Fentanyl’s death toll is risingScience News. Vol. 190. September 3, 2016, p. 14.