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Daniel Kohane of Boston Children's Hospital is developing drug delivery technologies that rely on nanoparticles and the spectrum of light.Getting drugs where they need to be, and at the right time, can be more challenging than you think. Tumors, for example, tend to have blood vessels that are tighter and twistier than normal ones, making it hard for drugs to penetrate them. Despite decades of research on antibodies, peptides and other guidance methods, drug makers struggle to target drugs to specific tissues or cell types.

And even once a drug arrives at the right place, the ability to fine-tune the dose so that the drug is released at the right time and in the right amount remains an elusive goal.

What’s needed is some kind of trigger, a stimulus that a clinician can turn on and off to guide when a drug is available and where it goes to make sure it does its job with the fewest side effects.

Daniel Kohane, MD, PhD, a critical care specialist and director of the Laboratory for Biomaterials and Drug Delivery at Boston Children’s Hospital, thinks he’s hit upon a promising trigger, one that’s all around us: light. Full story »

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Cameron with Galina Lipton, MD

By the time Cameron Shearing arrived at the South Shore Hospital Emergency Department (ED) during a December snowstorm, he wasn’t breathing. He didn’t have much time. The two-year-old had aspirated a chocolate-covered pretzel, which sent tiny bits of material into his lungs.

The odds of a good outcome were not high. Pretzel is one of the worst foods to aspirate for two reasons: The small pieces can block multiple small airways, and the salt, which is very irritating, causes a lot of inflammation.

“Cameron was one of the sickest patients I ever cared for as an emergency physician. I did everything I could within my scope of practice, but he needed the tools and expertise of pediatric subspecialists,” recalls Galina Lipton, MD, from Boston Children’s Department of Emergency Medicine, who was staffing the South Shore Hospital emergency room that evening. Full story »

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A clinician's-eye view of a patient with spinal muscular atrophy during a telemedicine visit.

A clinician's-eye view of a patient with spinal muscular atrophy during a telemedicine visit.

The jury is still out on telemedicine. Proponents and many patients appreciate its ability to deliver virtual patient care and to extend the reach of experts beyond the brick-and-mortar setting of a hospital. But the real question about telemedicine is: Does it make it difference? Does is it improve care and if so, in what circumstances?

TeleCAPE, a small pilot project at Boston Children’s Hospital, inches the dial toward “yes” for some patients—in particular, home-ventilated patients.

Home-ventilated patients require an inordinate amount of health care resources for even minor conditions. Costs for a simple urinary tract or viral respiratory infection that might be managed without hospitalization can reach up to $83,000 because the child’s complex medical needs require ICU admission. Full story »

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The platelet whisperers

by Tom Ulrich on March 27, 2014

Finding the switch that gets megakaryocytes to produce platelets

To manufacture platelets in the laboratory, we need to find the switch that starts their production.

Looking down at my bandaged finger—a souvenir of a kitchen accident a few nights prior—Joseph Italiano, PhD, smiles and says to me, “You should have come by, we could’ve given you some platelets for that.”

The problem is that Italiano really couldn’t; he needs every platelet his lab can put its hands on. A platelet biologist in Boston Children’s Hospital’s Vascular Biology Program, Italiano is trying to find ways to manufacture platelets at a clinically useful scale.

To do that, he needs to develop a deep understanding of the science of how the body produces platelets, something that no one has at the moment.

The path by which blood stem cells develop into megakaryocytes—the bone marrow cells that produce and release platelets into the bloodstream—is already known, Italiano says. We also know that platelets are essentially fragments of megakaryocytes that break off in response to some signal.

But that’s where our knowledge of platelet production largely ends. “Megakaryocytes themselves are something of a black box,” Italiano explains. “If you microinject the cytoplasm of an active megakaryocyte into a resting megakaryocyte, it will start to produce platelets as well. But we don’t know what factor or factors cause them to start platelet production.”

As Italiano and his laboratory peer into that black box, they know the stakes are big. Because in the end, they want to greatly reduce doctors’ and patients’ dependence on donated platelets. Full story »

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blood_vessel_shutterstock_142125664Chronic, unresolved inflammation can be quite harmful, right down to the cellular level. At the macro level, it has links to cancer, diabetes, heart disease and other degenerative conditions.

This is why the body keeps a tight rein on the inflammatory response and maintains a host of factors that resolve inflammation once the need for it (for instance, to clear an infection or heal an injury) has passed.

We know pretty well which factors work between cells to turn on and turn off inflammation. That knowledge has led to the development of drugs like ibuprofen, acetaminophen and naproxen, all of which temper pro-inflammatory factors.

However, when you look at the signals and signaling pathways within cells, things get more complex, especially when it comes to factors that turn off inflammation. We haven’t completely grasped the full complement of proteins that transmit these internal anti-inflammatory signals. If we did, we could potentially add new drugs to our pharmacopeia to regulate or resolve inflammation or maintain cells in a non-inflamed state, and perhaps help prevent rejection of transplanted organs and tissues.

David Briscoe, MD, and his team at Boston Children’s Hospital’s Transplant Research Program, has taken the field one step closer to grasping those internal pathways by studying a cellular protein called DEPTOR. Full story »

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Chest MRI and CT scans from a child

With the latest technologies and techniques, MRI (bottom) is in many cases just as good as, if not better than, CT (top) when taking images of a child's chest. (Courtesy Edward Y. Lee, MD, MPH)

Magnetic resonance imaging, or MRI, can produce stunningly detailed images of the body’s tissues and structures. Historically, however, the chest—and in particular, the lungs and airway—has proven challenging for radiologists to clearly visualize through MR images.

Why is that? Unlike most other solid organs, the lung and trachea aren’t really solid. The air spaces within them do not absorb the magnetic fields or produce the radio signals needed to generate high-quality diagnostic images. Also, they are in constant motion—we have to breathe, after all.

For these reasons, radiologists have long relied on x-rays and computed tomography (CT) scans to take pictures of the lungs. Both can produce very good, highly detailed diagnostic images, but both also come with risks related to their reliance on ionizing radiation.

The lung MRI’s time may now have come. In a review paper in Radiologic Clinics of North America (RCNA), an international team of radiologists led by Simon Warfield, PhD, and Edward Y. Lee, MD, MPH, of Boston Children’s Department of Radiology outlines several recent advances that have made MRI a more viable—radiation-free—alternative for diagnostic imaging of children’s lungs and airway. Full story »

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extended-spectrum B-lactamase

The discovery of penicillin in 1928 marked the beginning of the antibiotic era and dramatic improvements in health and medicine. With mass production of the new ‘wonder drug’ in the 1940s, threats from previously lethal diseases like bacterial infections and pneumonia waned. However, less than 100 years later, the Centers for Disease Control and Prevention (CDC) is sounding alarms about the increasing threat of antibiotic resistance.

The United States is edging closer to the cliff of a post-antibiotic era in which medications lose their effectiveness, the CDC cautioned in a September report, detailing the burden and threat posed by antibiotic-resistant bacteria.

Every year, more than 2 million people in the U.S. contract antibiotic-resistant infections, and at least 23,000 people die as a result. Estimates vary, but data suggest that the direct health care costs of antibiotic resistance may top $20 billion annually.

The path from remedy to resistance is rapid. “Every time antibiotics are used in any setting, bacteria evolve by developing resistance. This process can happen with alarming speed,” says Steve Solomon, MD, director of CDC’s Office of Antimicrobial Resistance. Full story »

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_InnovationSummit0106Boston Children’s Hospital convened the National Pediatric Innovation Summit + Awards 2013 with an ambitious goal: to bring together thought leaders to address the toughest challenges in pediatric health care. During the two-day summit, a series of panels and town hall discussions sparked dynamic dialogue.

While the summit was designed as a forum for ongoing discussion and relationship building, five key takeaways have emerged.            Full story »

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frassica

First-generation clinical decision support has been plagued by poor uptake among physicians, largely due to its overwhelming nature and perceived lack of applicability to clinical practice. But predictive analytics, built into these platforms, could produce the next significant wave in innovation in pediatric care, according to Joseph Frassica, MD, chief medical informatics officer and chief technology officer of Philips Healthcare.

Frassica spoke about predictive analytics last week at a panel on innovation acceleration at the Boston Children’s Hospital National Pediatric Innovation Summit + Awards 2013. Vector caught up with him afterward. Full story »

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A moment of levity as the panelists discuss health care challenges.

A moment of levity as the panelists discuss challenges in pediatric care and care delivery.

To summarize the state of pediatric health care today, Steven Altschuler, MD, president and CEO of Children’s Hospital of Philadelphia (CHOP), quoted the 1963 movie The Leopard: “Everything must change, so that everything can stay the same.”

He spoke at a panel discussion with two other children’s hospitals’ CEOs—Boston Children’s Hospital’s outgoing CEO James Mandell, MD, and Herman Gray, CEO of Children’s Hospital of Michigan (CHM)—during Boston Children’s Pediatric Health Innovation Summit + Awards on September 27 in Boston. Erik Halvorsen, PhD, director of Boston Children’s Technology and Innovation Development Office, moderated the session on the top challenges in pediatric health care and care delivery.

“For us to continue to support our missions in the traditional manner and for us to continue to advance pediatric health care, we need to change everything, including the reimbursement and research-funding models, as well as the education of our new caregivers,” Altschuler said. In his estimation, medical education has “unprepared new doctors and nurses to practice appropriate medicine in a safe, effective manner. The education is completely out of touch with reality.” Full story »

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