3-D printing is rapidly becoming a part of surgical planning. Since July 2013, Boston Children’s Hospital’s 3-D printing service, part of the Simulator Program, has received about 200 requests from 16 departments around the hospital. It’s generated a total of about 300 prints, most of them replicating parts of the body to be operated on.
Most prints take between 4 and 28 hours to produce. The largest to date—an entire malformed rib cage—took 105 hours and 35 minutes to create and weighed 8.9 pounds. The smallest—a tiny tangle of blood vessels in the brain—took 4 hours and 21 minutes and weighed 1.34 ounces. Here is sampling of what’s been coming off the production line.
Up to 80 percent of people with long-standing type 1 diabetes develop gastrointestinal symptoms—abdominal pain, bloating, nausea, vomiting, diarrhea, constipation and fecal incontinence—that severely diminish quality of life. Recent evidence suggests that this condition, known as diabetic enteropathy, results from damage to the intestinal lining, but the details beyond that have been unclear.
A study in this week’s Cell Stem Cell, led by Paolo Fiorina, MD, PhD, now provides some answers. It demonstrates how diabetes can lead to destruction of the stem cells that maintain the intestinal lining, and identifies a potential drug that could protect these stem cells and prevent or treat diabetic enteropathy.
The afterbirth has generally been an afterthought, but that’s about to change.
This week, 19 research centers were awarded grants from NIH’s Human Placenta Project, which is seeking to learn more about the intricate organ that sustained us in the womb, the interface between us and our mothers.
When 2015 MacArthur “genius” grant winner Beth Stevens, PhD, began studying the role of glia in the brain in the 1990s, these cells—“glue” from the Greek—weren’t given much thought. Traditionally, glia were thought to merely protect and support neurons, the brain’s real players.
But Stevens, from the Department of Neurology and the F.M. Kirby Neurobiology Center at Boston Children’s Hospital, has made the case that glia are key actors in the brain, not just caretakers. Her work—at the interface between the nervous and immune systems—is helping transform how neurologic disorders like autism, amyotrophic lateral sclerosis (ALS), Alzheimer’s disease and schizophrenia are viewed.
In early 2014, controversy erupted when two papers in Nature indicated that exposing ordinary cells to stress—an acid bath or mechanical stress—could quickly and efficiently turn them into pluripotent stem cells, capable of developing into virtually all the tissues in the body.
The technique, called “stimulus-triggered acquisition of pluripotency,” or STAP, was lauded for its simplicity compared to other methods like nuclear transfer into egg cells or cellular reprogramming with a set of transcription factors.
Gastroesophageal reflux disease (GERD), in which stomach acids back up into the esophagus, is increasingly diagnosed in children. One study based on insurance-claims data found that GERD diagnoses in infants more than tripled between 2000 and 2005 (from 3.4 to 12.3 percent). In addition to heartburn and chest pain, GERD has been implicated in cough, wheezing and pneumonia.
To reduce such acid-related symptoms, doctors increasingly prescribe acid suppression medications such as proton pump inhibitors (PPIs). They’re among the most-prescribed drug classes in the U.S. But clinicians in the Aerodigestive Program at Boston Children’s Hospital noticed that a large number of their GERD patients had lung cultures positive for bacteria, and that a strong predictor was the amount of non-acid reflux the child had.
“We then had to ask the question, ‘are acid suppression medications, which are being prescribed to treat respiratory symptoms, actually worsening the problem?’” says program director Rachel Rosen, MD, MPH. “What are these medications doing to change the bacteria composition in children?”
Prospects are looking up for patients who have no explanation for their symptoms despite extensive investigations and testing. There’s a growing revolution in DNA diagnostics (see yesterday’s example) and ongoing work to bring clarity and meaning to sequencing data. Patients with similar symptoms can find each other like never before, and are increasingly empowered to lead in research and discovery.
Another small but important development was announced yesterday by the National Institutes of Health. The NIH’s Undiagnosed Diseases Network (UDN) has opened up a one-stop online portal called the UDN Gateway where patients and families can apply for access to expert team analysis and testing. (A referral letter from a provider is required.)
The CLARITY Undiagnosed Challenge is heating up. Biomedical teams from seven countries are racing to interpret DNA sequences from five families affected with undiagnosed illnesses—some with gravely ill children, some already bereaved, all desperate for answers.
In July, the 26 competing teams received whole-genome and whole-exome sequence data from each patient and close family members, along with clinical notes and patient videos. Their reports, due September 21, will be judged by an independent panel based on:
the methods used to analyze and interpret the sequence data
the ability to synthesize the information
clinical usefulness, care recommendations and “next steps.”
Reports from parents and a growing number of studies over the past 10 to 15 years suggest that children with autism spectrum disorder (ASD), especially more severe ASD, are prone to gastrointestinal disorders. Researchers have attributed the association to altered GI microbiota, abnormal intestinal physiology, immune alterations and other mechanisms. Some speculate that the connection results from unusual eating patterns in children with ASD.
Looking at IBD (Crohn’s and colitis) sets the bar a little higher, since IBD is uncommon and also unlikely to be caused by dietary factors (though it can certainly be aggravated by them). In a new study in the journal Inflammatory Bowel Disease, Kohane and colleagues crunched three large databases to create what they believe is the largest ASD/IBD study to date.
Four children with life-threatening malformations of blood vessels in the brain appear to be the first to benefit from 3D printing of their anatomy before undergoing high-risk corrective procedures.
The children, ranging from 2 months to 16 years old, all posed particular treatment challenges: cerebrovascular disease often entails complex tangles of vessels in sensitive brain areas.
“These children had unique anatomy with deep vessels that were very tricky to operate on,” says Boston Children’s neurosurgeon Edward Smith, MD, senior author of the paper and co-director of the hospital’s Cerebrovascular Surgery and Interventions Center. “The 3D-printed models allowed us to rehearse the cases beforehand and reduce operative risk as much as we could. You can physically hold the 3D models, view them from different angles, practice the operation with real instruments and get tactile feedback.”