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Scientists move closer to developing therapeutic window to the brain

Researchers at the University of California, Riverside are bringing their idea for a ‘Window to the Brain’ transparent skull implant closer to reality through the findings of two studies that are forthcoming in the journals Lasers in Surgery and Medicine and Nanomedicine: Nanotechnology, Biology and Medicine.

The implant under development, which literally provides a ‘window to the brain,’ will allow doctors to deliver minimally invasive, laser-based treatments to patients with life-threatening neurological disorders, such as brain cancers, traumatic brain injuries, neurodegenerative diseases and stroke. The recent studies highlight both the biocompatibility of the implant material and its ability to endure bacterial infections.

The Window to the Brain project is a multi-institution, interdisciplinary partnership led by Guillermo Aguilar, professor of mechanical engineering in UCR’s Bourns College of Engineering, and Santiago Camacho-López, from the Centro de Investigación Científica y de Educación Superior de Ensenada (CICESE) in Mexico.

The project began when Aguilar and his team developed a transparent version of the material yttria-stabilized zirconia (YSZ) — the same ceramic product used in hip implants and dental crowns. By using this as a window-like implant, the team hopes doctors will be able to aim laser-based treatments into patients’ brains on demand and without having to perform repeated craniotomies, which are highly invasive procedures used to access the brain.

The internal toughness of YSZ, which is more impact resistant than glass-based materials developed by other researchers, also makes it the only transparent skull implant that could conceivably be used in humans. The two recent studies further support YSZ as a promising alternative for currently available cranial implants.

Published July 8 in Lasers in Surgery and Medicine, the most recent study demonstrates how the use of transparent YSZ may allow doctors to combat bacterial infections, which are a leading reason for cranial implant failure. In lab studies, the researchers treated E-Coli infections by aiming laser light through the implant without having to remove it and without damaging the surrounding tissues.

“This was an important finding because it showed that the combination of our transparent implant and laser-based therapies enables us to treat not only brain disorders, but also to tackle bacterial infections that are common after cranial implants. These infections are especially challenging to treat because many antibiotics do not penetrate the blood brain barrier,” said Devin Binder, M.D., a neurosurgeon and neuroscientist in UCR’s School of Medicine and a collaborator on the project.

Another recent study, published in the journal Nanomedicine: Nanotechnology, Biology and Medicine, explored the biocompatibility of YSZ in an animal model, where it integrated into the host tissue without causing an immune response or other adverse effects.

“The YSZ was actually found to be more biocompatible than currently available materials, such as titanium or thermo-plastic polymers, so this was another piece of good news in our development of transparent YSZ as the material of choice for cranial implants,” Aguilar said.

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https://www.sciencedaily.com/releases/2016/07/160712133916.htm Original web page at Science Daily

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From a heart in a backpack to a heart transplant

All transplant patients are exceptional, but Stan Larkin’s successful heart transplant comes after living more than a year without a human heart and relying on a heart device he carried in a backpack.

The first patient in Michigan ever discharged with a SynCardia temporary total artificial heart in 2014, Larkin was back at the University of Michigan Frankel Cardiovascular Center in May for a heart transplant.

The surgery performed by Jonathan Haft, M.D., was a unique national triumph in efforts to replace the failing heart as heart disease grows and donor hearts remain scarce.

“It was an emotional rollercoaster,” Larkin, 25, said at a news conference when he described living with the total artificial heart that was implanted to keep him alive until a donor heart became available.

“I got the transplant two weeks ago and I feel like I could take a jog as we speak. I want to thank the donor who gave themselves for me. I’d like to meet their family one day. Hopefully they’d want to meet me.”

Stan’s older brother Dominique also relied on a TAH before a heart transplant in 2015. The brothers were diagnosed as teenagers with familial cardiomyopathy, a type of heart failure that can strike seemingly healthy people without warning. It’s linked to a leading cause of sudden death among athletes.

“They were both very, very ill when we first met them in our intensive care units,” says Haft, associate professor of cardiac surgery. “We wanted to get them heart transplants, but we didn’t think we had enough time. There’s just something about their unique anatomic situation where other technology wasn’t going to work.”

The temporary total artificial heart is used when both sides of the heart fail, and more common heart-supporting devices are not adequate to keep patients alive.

Rather than stay in the hospital, Larkin used a wearable, 13.5 pound Freedom® portable driver to keep the artificial heart going.

“He really thrived on the device,” Haft said looking at a photo of Stan on a basketball court. “This wasn’t made for pick-up basketball,” he joked.

As Haft teaches at the University of Michigan Medical School, the brothers have joined him to share the impact that circulatory support can have on those with end-stage heart failure.

Of the 5.7 million Americans living with heart failure, about 10 percent have advanced heart failure, according to the American Heart Association.

“You’re heroes to all of us,” says David J. Pinsky, M.D., a director of the U-M Frankel Cardiovascular Center. “The fact that you take your story public and allow us to teach others makes a difference. You’ll make a difference for a lot of patients. You’ll make a difference to the doctors of the future. We thank you for allowing us to share your story and your bravery in sharing it.”

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/06/160603072131.htm Original web page at Science Daily

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Supervised autonomous in vivo robotic surgery on soft tissues is feasible

The study, published today in Science Translational Medicine, reports the results of soft tissue surgeries conducted on both inanimate porcine tissue and living pigs using proprietary robotic surgical technology, Smart Tissue Autonomous Robot (STAR), developed at Children’s National. This technology removes the surgeon’s hands from the procedure, instead utilizing the surgeon as supervisor, with soft tissue suturing autonomously planned and performed by the STAR robotic system.

Soft tissues are the tissues that connect, support or surround other structures and organs of the body such as tendons, ligaments, fascia, skin, fibrous tissues, fat, synovial membranes, muscles, nerves and blood vessels. Currently more than 44.5 million soft tissue surgeries are performed in the U.S. each year.

“Our results demonstrate the potential for autonomous robots to improve the efficacy, consistency, functional outcome and accessibility of surgical techniques,” said Dr. Peter C. Kim, Vice President and Associate Surgeon-in-Chief, Sheikh Zayed Institute for Pediatric Surgical Innovation. “The intent of this demonstration is not to replace surgeons, but to expand human capacity and capability through enhanced vision, dexterity and complementary machine intelligence for improved surgical outcomes.”

While robot-assisted surgery (RAS) has increased in adoption in healthcare settings, the execution of soft tissue surgery has remained entirely manual, largely because the unpredictable, elastic and plastic changes in soft tissues that occur during surgery, requiring the surgeon to make constant adjustments.

To overcome this challenge, STAR uses a tracking system that integrates near infrared florescent (NIRF) markers and 3D plenoptic vision, which captures light field information to provide images of a scene in three dimensions. This system enables accurate, uninhibited tracking of tissue motion and change throughout the surgical procedure. This tracking is combined with another STAR innovation, an intelligent algorithm that guides the surgical plan and autonomously makes adjustments to the plan in real time as tissue moves and other changes occur. The STAR system also employs force sensing, submillimeter positioning and actuated surgical tools. It has a bed-side lightweight robot arm extended with an articulated laparoscopic suturing tool for a combined eight degrees-of-freedom robot.

“Until now, autonomous robot surgery has been limited to applications with rigid anatomy, such as bone cutting, because they are more predictable,” said Axel Krieger, PhD, and technical lead for Smart Tools at Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National. “By using novel tissue tracking and applied force measurement, coupled with suture automation software, our robotic system can detect arbitrary tissue motions in real time and automatically adjust.”

To compare the effectiveness of STAR to other available surgical procedures, the study included two different surgeries performed on inanimate porcine tissue (ex vivo), linear suturing and an end-to-end intestinal anastomosis, which involves connecting the tubular loops of the intestine. The results of each surgery were compared with the same surgical procedure conducted manually by an experienced surgeon, by laparoscopy, and by RAS with the daVinci Surgical System.

Intestinal anastomosis was the surgical procedure conducted on the living subjects (in vivo) in the study. The Children’s National research team conducted four anastomosis surgeries on living pigs using STAR technology and all subjects survived with no complications. The study compared these results to the same procedure conducted manually by an experienced surgeon using standard surgical tools.

“We chose the complex task of anastomosis as proof of concept because this soft tissue surgery is performed over one million times in the U.S. annually,” said Dr. Kim.

All surgeries were compared based on the metrics of anastomosis including the consistency of suturing based on average suture spacing, the pressure at which the anastomosis leaked, the number of mistakes that required removing the needle from the tissue, completion time and lumen reduction, which measures any constriction in the size of the tubular opening.

The comparison showed that supervised autonomous robotic procedures using STAR proved superior to surgery performed by experienced surgeons and RAS techniques, whether on static porcine tissues or on living specimens, in areas such as consistent suture spacing, which helps to promote healing, and in withstanding higher leak pressures, as leakage can be a significant complication from anastomosis surgery. Mistakes requiring needle removal were minimal and lumen reduction for the STAR surgeries was within the acceptable range.

In the comparison using living subjects, the manual control surgery took less time, eight minutes versus 35 minutes for the fastest STAR procedure, however researchers noted that the duration of the STAR surgery was comparable to the average for clinical laparoscopic anastomosis, which ranges from 30 minutes to 90 minutes, depending on complexity of the procedure.

Dr. Kim said that since supervised, autonomous robotic surgery for soft tissue procedures has been proven effective, a next step in the development cycle would be further miniaturization of tools and improved sensors to allow for wider use of the STAR system.

He added that, with the right partner, some or all of the technology can be brought into the clinical space and bedside within the next two years.

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/05/160504151855.htm Original web page at Science Daily

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Researchers one step closer to understanding regeneration in mammals

A long-standing question in biology is why humans have poor regenerative ability compared to other vertebrates? While tissue injury normally causes us to produce scar tissue, why can’t we regenerate an entire digit or piece of skin? A group of University of Kentucky researchers is one step closer to answering these questions after studying a unique mammal, and its ears.

The team’s new findings come on the heels of UK Assistant Professor of Biology Ashley Seifert’s landmark discovery in 2012 that two species of African spiny mice found in Kenya could regenerate damaged skin. The group built on this work to show that a third species of spiny mouse, Acomys cahirinus, could completely close four millimeter ear holes and regenerate the missing tissue. Their recent work examined repair of ear holes across a number of different mammals and revealed that regeneration appears to be a unique trait.

While three species of wild African spiny mice and New Zealand white rabbits were capable of regenerating ear tissue, outbred laboratory mice and inbred strains such as the MRL healer mice failed to do so and instead healed the wounds by scarring.

“First we need to understand how mammalian regeneration works in a natural setting, then comes the potential to create therapeutic treatments for humans,” said Thomas Gawriluk, postdoctoral scholar and co-lead author of the study.

This new study suggests that genetic factors underlie variation in regenerative ability. Unlike many previous assumptions that there is a magic bullet for regeneration, like the presence of a specific gene, the group’s comprehensive genetic analysis shows that it is a complex trait. Importantly, cellular and molecular analysis by Seifert’s group has now demonstrated that spiny mice regenerate ear tissue by forming a blastema. Methodical demonstration of a blastema was important to place spiny mice in the context of regeneration in other vertebrates.

“These findings show that tissue regeneration in African spiny mice is similar to that described for other vertebrate regenerators like salamanders and zebrafish, giving us a powerful framework to understand mammalian regeneration,” said Seifert.

Rigorous examination of this mammalian model is the first stage in figuring out molecular mechanisms that govern regenerative processes, which could have a significant impact on regenerative medicine for humans. Many regeneration biologists believe that inducing a blastema in humans would be a major step towards stimulating tissue regeneration.

“The regenerative healing response of the spiny mouse is truly remarkable and Dr. Seifert’s new work provides clear evidence that regenerative capabilities have evolved among rodents,” said Ken Muneoka, professor at Texas A&M University and a pioneer in the field of regeneration. “The spiny mouse represents one of only a handful of regeneration models in mammals that can be used to uncover basic strategies to enhance the regenerative capacity of humans.”

https://www.sciencedaily.com/  Science Daily

://www.sciencedaily.com/releases/2016/04/160425100548.htm  Original web page at Science Daily

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* Much longer survival for heart transplants across species

A new immune-suppressing therapy has led to the longest survival yet for a cross-species heart transplant, according to new research conducted in part by researchers at the University of Maryland School of Medicine (UM SOM).

The study involved transplanting pig hearts into baboons. The results could lead to increased use of xenotransplantation, the transplantation of organs from one species to another. Researchers hope this approach could eventually be used in humans, helping the severe organ shortage among patients awaiting transplantation.

The study, which was conducted at the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, was published yesterday in Nature Communications.

A key problem with using xenotransplantion with humans is that the immune system reacts very strongly, which can cause organ rejection. Scientists have tried modifying the organ donor’s genes and developing novel immune-suppressing drugs for the organ recipients.

In the current study, scientists developed a novel immune-suppressing drug regimen that includes a key antibody, called anti-CD40 antibody, which may help the organ resist the immune system response. The researchers used pigs that had been genetically modified to have high immune system tolerance and then transplanted hearts from these animals into a group of five baboons. The pig heart did not replace the baboon heart, but was an additional organ. Both the new and original hearts continued to pump blood.

With the new immune-suppressing drugs, the pig hearts survived for up to 945 days in the baboons — much longer than previous pig-to-primate heart transplants. The immune-suppressing drugs played a key role in this.

“This has the potential to really move the field forward,” said Richard Pierson, a professor of surgery at UM SOM, one of the co-authors. He has studied xenotransplantation for three decades. “This new approach clearly made a difference. We obviously have a lot more work to do, but I’m confident that eventually this will be useful to human patients.”

The study’s lead author was Muhammad Mohiuddin, MD, chief of the transplantation section in the Cardiothoracic Surgery Research Program at the NHLBI.

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/04/160406140334.htm  Original web page at Science Daily

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* New esophagus tissue reconstructed

US doctors report reconstructing new esophagus tissue in a critically ill patient. Writing in The Lancet, US doctors report the first case of a human patient whose severely damaged esophagus was reconstructed using commercially available FDA approved stents and skin tissue. Seven years after the reconstruction and 4 years after the stents were removed, the patient continues to eat a normal diet and maintain his weight with no swallowing problems.

Until now, this regeneration technique has only been tested in animals. The authors, reporting on the outcome of the procedure, say that research, including animal studies and clinical trials, are now needed to investigate whether the technique can be reproduced and used in other similar cases.

Professor Kulwinder Dua from the Medical College of Wisconsin, Milwaukee, USA, and colleagues report using metal stents as a non-biological scaffold and a regenerative tissue matrix from donated human skin to rebuild a full-thickness 5cm defect in the esophagus of a 24-year-old man. The patient was urgently admitted to hospital with a disrupted esophagus resulting in life-threatening infection and inability to swallow following complications from an earlier car accident which had left him partially paralysed. Despite several surgeries, the defect in the esophagus was too large to repair.

The esophagus is a hollow muscular tube that connects the mouth to the stomach carrying food and liquids. Removal of the esophagus (esophagectomy) to treat cancer or injury requires reconnecting the remaining part of the esophagus to the stomach to allow swallowing and the passage of food. Part of the stomach or colon is used to make this connection. However, the procedure was not possible in this case because the defect in the esophagus was too large, and the patient too ill to undergo the procedure.

The team hypothesized that if the three-dimensional shape of the esophagus could be maintained in its natural environment for an extended period of time while stimulating regeneration using techniques previously validated in animals, esophageal reconstruction may be possible.

They used commercially available, FDA-approved, materials to repair the defect. To maintain the shape of the esophagus and bridge the large defect, they used an endoscope to place self-expanding metal stents. The defect was then surgically covered with regenerative tissue matrix and sprayed with a platelet-rich plasma gel produced from the patient’s own blood to deliver high concentrations of growth factors that not only stimulate growth but also attract stem cells to stimulate healing and regeneration. The sternocleidomastoid, a muscle running along the side of the neck, was placed over the matrix and the adhesive platelet-rich plasma gel.

The team planned on removing the stent 12 weeks after reconstruction, but the patient delayed the procedure for three and a half years because of fears of developing a narrowing or leakage in the esophagus. One year after the stents were removed, endoscopic ultrasound images showed areas of fibrosis (scarring) and regeneration of all five layers of the esophageal wall. Full recovery of functioning was also established by swallowing tests showing that esophageal muscles were able to propel water and liquid along the esophagus into the stomach in both upright and 45° sitting positions. But, how long the regeneration process took is unclear because the patient delayed stent removal for several years.

According to Professor Dua, “This is a first in human operation and one that we undertook as a life-saving measure once we had exhausted all other options available to us and the patient. The use of this procedure in routine clinical care is still a long way off as it requires rigorous assessment in large animal studies and phase 1 and 2 clinical trials. The approach we used is novel because we used commercially available products which are already approved for use in in the human body and hence didn’t require complex tissue engineering.”

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/04/160409091725.htm  Original web page at Science Daily

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Tiny electronic implants monitor brain injury, then melt away

A new class of small, thin electronic sensors can monitor temperature and pressure within the skull — crucial health parameters after a brain injury or surgery — then melt away when they are no longer needed, eliminating the need for additional surgery to remove the monitors and reducing the risk of infection and hemorrhage.

Similar sensors can be adapted for postoperative monitoring in other body systems as well, the researchers say. Led by John A. Rogers, a professor of materials science and engineering at the University of Illinois at Urbana-Champaign, and Wilson Ray, a professor of neurological surgery at the Washington University School of Medicine in St. Louis, the researchers publish their work in the journal Nature on January 18.

“This is a new class of electronic biomedical implants,” said Rogers, who directs the Frederick Seitz Materials Research Laboratory at Illinois. “These kinds of systems have potential across a range of clinical practices, where therapeutic or monitoring devices are implanted or ingested, perform a sophisticated function, and then resorb harmlessly into the body after their function is no longer necessary.”

After a traumatic brain injury or brain surgery, it is crucial to monitor the patient for swelling and pressure on the brain. Current monitoring technology is bulky and invasive, Rogers said, and the wires restrict the patent’s movement and hamper physical therapy as they recover. Because they require continuous, hard-wired access into the head, such implants also carry the risk of allergic reactions, infection and hemorrhage, and even could exacerbate the inflammation they are meant to monitor.

“If you simply could throw out all the conventional hardware and replace it with very tiny, fully implantable sensors capable of the same function, constructed out of bioresorbable materials in a way that also eliminates or greatly miniaturizes the wires, then you could remove a lot of the risk and achieve better patient outcomes,” Rogers said. “We were able to demonstrate all of these key features in animal models, with a measurement precision that’s just as good as that of conventional devices.”

The new devices incorporate dissolvable silicon technology developed by Rogers’ group at the U. of I. The sensors, smaller than a grain of rice, are built on extremely thin sheets of silicon — which are naturally biodegradable — that are configured to function normally for a few weeks, then dissolve away, completely and harmlessly, in the body’s own fluids.

Rogers’ group teamed with Illinois materials science and engineering professor Paul V. Braun to make the silicon platforms sensitive to clinically relevant pressure levels in the intracranial fluid surrounding the brain. They also added a tiny temperature sensor and connected it to a wireless transmitter roughly the size of a postage stamp, implanted under the skin but on top of the skull.

The Illinois group worked with clinical experts in traumatic brain injury at Washington University to implant the sensors in rats, testing for performance and biocompatibility. They found that the temperature and pressure readings from the dissolvable sensors matched conventional monitoring devices for accuracy.

“The ultimate strategy is to have a device that you can place in the brain — or in other organs in the body — that is entirely implanted, intimately connected with the organ you want to monitor and can transmit signals wirelessly to provide information on the health of that organ, allowing doctors to intervene if necessary to prevent bigger problems,” said Rory Murphy, a neurosurgeon at Washington University and co-author of the paper. “After the critical period that you actually want to monitor, it will dissolve away and disappear.”

The researchers are moving toward human trials for this technology, as well as extending its functionality for other biomedical applications.

“We have established a range of device variations, materials and measurement capabilities for sensing in other clinical contexts,” Rogers said. “In the near future, we believe that it will be possible to embed therapeutic function, such as electrical stimulation or drug delivery, into the same systems while retaining the essential bioresorbable character.”

http://www.sciencedaily.com/  Science Daily

http://www.sciencedaily.com/releases/2016/01/160118134431.htm  Original web page at Science Daily

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Personalized heart models for surgical planning

System can convert MRI scans into 3-D-printed, physical models in a few hours. Researchers at MIT and Boston Children’s Hospital have developed a system that can take MRI scans of a patient’s heart and, in a matter of hours, convert them into a tangible, physical model that surgeons can use to plan surgery.

The models could provide a more intuitive way for surgeons to assess and prepare for the anatomical idiosyncrasies of individual patients. “Our collaborators are convinced that this will make a difference,” says Polina Golland, a professor of electrical engineering and computer science at MIT, who led the project. “The phrase I heard is that ‘surgeons see with their hands,’ that the perception is in the touch.”

This fall, seven cardiac surgeons at Boston Children’s Hospital will participate in a study intended to evaluate the models’ usefulness. Golland and her colleagues will describe their new system at the International Conference on Medical Image Computing and Computer Assisted Intervention in October. Danielle Pace, an MIT graduate student in electrical engineering and computer science, is first author on the paper and spearheaded the development of the software that analyzes the MRI scans. Medhi Moghari, a physicist at Boston Children’s Hospital, developed new procedures that increase the precision of MRI scans tenfold, and Andrew Powell, a cardiologist at the hospital, leads the project’s clinical work.

MRI data consist of a series of cross sections of a three-dimensional object. Like a black-and-white photograph, each cross section has regions of dark and light, and the boundaries between those regions may indicate the edges of anatomical structures. Then again, they may not.

Determining the boundaries between distinct objects in an image is one of the central problems in computer vision, known as “image segmentation.” But general-purpose image-segmentation algorithms aren’t reliable enough to produce the very precise models that surgical planning requires.

Typically, the way to make an image-segmentation algorithm more precise is to augment it with a generic model of the object to be segmented. Human hearts, for instance, have chambers and blood vessels that are usually in roughly the same places relative to each other. That anatomical consistency could give a segmentation algorithm a way to weed out improbable conclusions about object boundaries.

The problem with that approach is that many of the cardiac patients at Boston Children’s Hospital require surgery precisely because the anatomy of their hearts is irregular. Inferences from a generic model could obscure the very features that matter most to the surgeon.

In the past, researchers have produced printable models of the heart by manually indicating boundaries in MRI scans. But with the 200 or so cross sections in one of Moghari’s high-precision scans, that process can take eight to 10 hours.

“They want to bring the kids in for scanning and spend probably a day or two doing planning of how exactly they’re going to operate,” Golland says. “If it takes another day just to process the images, it becomes unwieldy.

Pace and Golland’s solution was to ask a human expert to identify boundaries in a few of the cross sections and allow algorithms to take over from there. Their strongest results came when they asked the expert to segment only a small patch –one-ninth of the total area — of each cross section.

In that case, segmenting just 14 patches and letting the algorithm infer the rest yielded 90 percent agreement with expert segmentation of the entire collection of 200 cross sections. Human segmentation of just three patches yielded 80 percent agreement.

“I think that if somebody told me that I could segment the whole heart from eight slices out of 200, I would not have believed them,” Golland says. “It was a surprise to us.” Together, human segmentation of sample patches and the algorithmic generation of a digital, 3-D heart model takes about an hour. The 3-D-printing process takes a couple of hours more.

Currently, the algorithm examines patches of unsegmented cross sections and looks for similar features in the nearest segmented cross sections. But Golland believes that its performance might be improved if it also examined patches that ran obliquely across several cross sections. This and other variations on the algorithm are the subject of ongoing research.

The clinical study in the fall will involve MRIs from 10 patients who have already received treatment at Boston Children’s Hospital. Each of seven surgeons will be given data on all 10 patients — some, probably, more than once. That data will include the raw MRI scans and, on a randomized basis, either a physical model or a computerized 3-D model, based, again at random, on either human segmentations or algorithmic segmentations.

Using that data, the surgeons will draw up surgical plans, which will be compared with documentation of the interventions that were performed on each of the patients. The hope is that the study will shed light on whether 3-D-printed physical models can actually improve surgical outcomes.

http://www.sciencedaily.com/  Science Daily

http://www.sciencedaily.com/releases/2015/09/150917130030.htm  Original web page at Science Daily

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Reducing emergency surgery cuts health care costs

Researchers have determined the hospital costs and risk of death for emergency surgery and compared it to the same operation when performed in a planned, elective manner for three common surgical procedures: abdominal aortic aneurysm repair, coronary artery bypass graft and colon resection. The research indicates that reducing emergency surgery for three common procedures by 10 percent could cut $1 billion in health care costs over 10 years. As hospitals and health systems increasingly focus on addressing the rising cost of health care in the United States, and with the expense of surgical care playing a major role, physician researchers and others across the healthcare industry are working to identify innovative ways to reduce surgical costs. In new findings published online in the journal Annals of Surgery on December 19, 2014, researchers determined the hospital costs and risk of death for emergency surgery and compared it to the same operation when performed in a planned, elective manner for three common surgical procedures: abdominal aortic aneurysm repair, coronary artery bypass graft and colon resection. “If 10 percent of these emergency surgeries had been performed electively, the cost difference would have been nearly $1 billion over 10 years,” said Adil Haider, MD, MPH, director of the Center for Surgery and Public Health at Brigham and Women’s Hospital (BWH) and lead author of the paper. “Importantly, elective procedures are better for patients, too, who experience lower rates of mortality and better outcomes. There is a tremendous opportunity to both save lives and decrease costs.” Haider, who conducted this research while at the Center for Surgical Trials and Outcomes Research at Johns Hopkins, with colleagues from Howard University, analyzed data from a nationally representative sample of 621,925 patients from 2001 to 2010 who underwent abdominal aortic aneurysm repair, coronary artery bypass graft and colon resection. The hospital’s cost to care for these patients was calculated with standardized information on inpatient cost and charge as reported by hospitals to the Center for Medicare and Medicaid. When compared to elective surgery, emergency surgery was 30 percent more expensive for abdominal aortic aneurysm repair, 17 percent more expensive for coronary artery bypass graft and 53 percent more expensive for colon resection. Researchers also found that patients who underwent elective surgery had significantly lower rates of mortality compared to those who had emergency surgical procedures. “The costs of surgical care represent nearly 30 percent of total healthcare expenditures and they are projected to total more than $900 billion by 2025, said Haider. “As we, collectively in the healthcare industry, work to systematically address the rising cost of healthcare, reducing emergency surgeries for common procedures provides a significant opportunity that must be seriously and thoughtfully considered. Strategically aligning primary care, screening programs and other interventions could be an impactful way to both improve outcomes and reduce costs.”

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http://www.sciencedaily.com/releases/2014/12/141219160558.htm Original web page at Science Daily

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* Investigations launched into artificial tracheas

One of Europe’s most prestigious medical universities, the Karolinska Institute in Stockholm, has launched two investigations into the clinical procedures of a doctor famed for performing potentially revolutionary, bioengineered trachea transplants. Since 2008, Paolo Macchiarini, a thoracic surgeon at the Karolinska Institute, has replaced parts of airways damaged by injury, cancer or other disorders in 17 patients. In the earlier cases, he transplanted parts of tracheas taken from cadavers; in his later work, he transplanted synthetic tracheas. In both procedures, before transplantation, he would treat the tracheas with stem cells taken from the patient’s bone marrow, which he says helps the transplants to act like biological tissue. Bioengineering experts contacted by Nature say that Macchiarini’s procedures were considered a great leap for their nascent field because tracheas demand a high level of biological function — including the ability to defend against the constant assault of inhaled bacteria and to form a seal with the adjoining airway tissue. Macchiarini’s reports were a “bright spot” for the field, says David Mooney, a bioengineering specialist at Harvard University in Cambridge, Massachusetts. One of the investigations is being conducted by an external expert in the relevant fields, who is due to report the findings on 15 January. It focuses on the three procedures that Macchiarini carried out at the Karolinska Institute, all of which involve artificial tracheas. The investigation comes in response to a report filed in August by four thoracic doctors at the affiliated Karolinska Hospital — Matthias Corbascio, Thomas Fux, Karl-Henrik Grinnemo and Oscar Simonson — who helped to treat the three patients. The doctors compared results in a paper Macchiarini published in The Lancet (Lancet 378,1997–2004; 2011), describing the first use of a synthetic trachea seeded with stem cells, with the medical records of the patient. According to the doctors, there are discrepancies. For example, the Lancet paper says that the synthetic trachea was “partly covered by nearly healthy epithelium”, indicating the growth of a protective cell layer, whereas the doctors say they could find no evidence in biopsy reports for healthy growth. The paper also says that the implanted trachea showed signs of tight connection with the adjacent tissue and that it was acting like “an almost normal airway”, whereas bronchoscopy reports note gaps between the trachea and the bronchus, the tube that leads from the trachea to the lungs, and the need for stents to stabilize the airway. “The problems alluded to are irreconcilable with the published reports,” says one US-based thoracic surgeon who reviewed the report but asked not to be named. Macchiarini says that he will not reply to specific questions about alleged discrepancies between his publications and the medical records yet, because the allegations against him “now have to be investigated by an external expert, which is the normal process following cases of accusations of scientific misconduct”. He adds: “I certainly do welcome that investigation.” He is confident that “there is nothing suspect, unethical, inflated or misleading about anything I have done or reported”.

The Lancet says: “At this stage, we can’t comment on the allegations regarding Dr Macchiarini’s procedures.” The complaint filed by the four doctors also claims that there were no informed-consent forms in the medical records for two of the three procedures carried out at the Karolinska Hospital. The one form on record was signed 17 days after the procedure. Macchiarini says:“Of course there was consent. We would never have proceeded with the transplants if there wasn’t.” He adds: “I do not know why the form is dated 17 days after the procedure and can only assume it is some kind of clerical issue.” The patient “signed it in my presence, prior to the operation”. He adds that “there was absolutely no ethical breach”. The Karolinska Institute’s ethics council, meanwhile, is carrying out the second investigation, which was launched in response to a report it received in June from Pierre Delaere, a head and neck surgeon at the University Hospital, KU Leuven, Belgium. Delaere complains, for example, that published descriptions of the transplants minimize complications faced by patients, such as the need for stents. In August, Macchiarini sent a 15-page response to the Karolinska, acknowledging that he had “shortened” discussion of complications because “of the editor’s requirements during the review process”. But overall, he maintains that “all aspects of the patients’ outcomes are discussed in detail”. In an accompanying letter, Macchiarini says that he has “thoroughly reviewed” Delaere’s allegations and believes that they are “unfounded”. The ethics council plans to interview the concerned parties during January, and to give recommendations to the vice-chancellor of the Karolinska Institute, Anders Hamsten, by the end of February at the earliest. Hamsten will then decide how to proceed. Hamsten says that the institute had initiated investigations into Macchiarini’s publications twice in the past, following allegations of scientific misconduct from other complainants. Both investigations concluded — one in July 2013, the other in September 2014 — that there was no scientific misconduct. Macchiarini, who is currently spending part of his time at the Kuban State Medical University in Krasnodar, Russia, leading a project into the regeneration of lung airways, recently put on hold his own trial there into the use of synthetic tracheas after the death of a patient on 20 September 2014. The patient had had a synthetic transplant in June 2012 and, when that one began to fail, another in August 2013. Macchiarini told Nature that the patient’s doctor has now reported the cause of death as “bilateral acute pneumonia with heart–lung insufficiency”, which he says is unrelated to the trachea transplant. He says that she was “breathing normally and asymptomatic” two weeks before her death. “We will be considering the restarting of the clinical trial now that this cause has been ascertained,” he told Nature. The most recent of Macchiarini’s total of eight synthetic trachea-transplant patients, who was operated on in June, “is doing very well, is asymptomatic”, he says. Six have died, with their post-transplant life-spans ranging from 3 to 31 months. Macchiarini says that one died because of complications following an accident, another from drinking too much alcohol, and another from “respiratory failure and subsequent multi-system organ failure”. In none, he says, has the death been linked to the transplant. The remaining patient has been in intensive care ever since her procedure, more than two years ago. Macchiarini says this is not a result of the procedure. “When this patient came to Karolinska, her situation was dire,” he says. “Her doctors gave her a life expectancy of 3 to 6 months.” He also says that the surgery revealed more extensive damage to her airways than had been apparent from the examination before the operation. The damage could not have been diagnosed before the surgery, he says. Nine other patients have received tracheas from cadavers. According to a paper by Macchiarini this year, four of those patients have died, either from recurrence of tumours or from gastrointestinal bleeding. Of the five still living, the paper reports that four are dependent on stents, and one has no need for stents (P. Jungebluth and P. Macchiarini Thorac. Surg. Clin. 24, 97–106; 2014). Macchiarini emphasizes that the procedure is experimental. “Given the nature of this work, we are not in a position to guarantee them long-term survival and they are all abundantly aware of that going in,” he says. “We at least give them a chance, a chance at a longer life, and the hope of being the patient who survives long-term.”

Nature 516, 16–17 (04 December 2014) doi:10.1038/516016a

http://www.nature.com/news/index.html  Nature

http://www.nature.com/news/investigations-launched-into-artificial-tracheas-1.16431  Original web page at Nature

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Promise for new nerve repair technique

Traumatic nerve injuries are common, and when nerves are severed, they do not heal on their own and must be repaired surgically. Injuries that are not clean-cut — such as saw injuries, farm equipment injuries, and gunshot wounds — may result in a gap in the nerve. To fill these gaps, surgeons have traditionally used two methods: a nerve autograft (bridging the gap with a patient’s own nerve taken from elsewhere in the body), which leads to a nerve deficit at the donor site; or nerve conduits (synthetic tubes), which can cause foreign body reactions or infections. The prospective, randomized study, conducted by UK Medical Director of Hand Surgery Service Dr. Brian Rinker and others, compared the nerve conduit to a newer technique called a nerve allograft. The nerve allograft uses human nerves harvested from cadavers. The nerves are processed to remove all cellular material, preserving their architecture while preventing disease transmission or allergic reactions. Participants with nerve injuries were randomized into either conduit or allograft repair groups. Following the surgeries, independent blind observers performed standardized assessments at set time points to determine the degree of sensory or motor recovery. The results of the study suggested that nerve allografts had more consistent results and produced better outcomes than nerve conduits, while avoiding the donor site morbidity of a nerve autograft. Rinker, a principal investigator of the study, describes it as a “game-changer.” “Nerve grafting has remained relatively unchanged for nearly 100 years, and both of the existing nerve repair options had serious drawbacks,” Rinker said. “Our study showed that the new technique processed nerve allograft ­- provides a better, more predictable and safer nerve gap repair compared to the previous techniques.”

http://www.sciencedaily.com/  Science Daily

http://www.sciencedaily.com/releases/2014/08/140808163451.htm  Original web page at Science Daily

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* Stem cells aid heart regeneration in salamanders

Imagine filling a hole in your heart by regrowing the tissue. While that possibility is still being explored in people, it is a reality in salamanders. A recent discovery that newt hearts can regenerate may pave the way to new therapies in people who need to have damaged tissue replaced with healthy tissue. Heart disease is the leading cause of deaths in the United States. Preventative measures like healthful diets and lifestyles help ward off heart problems, but if heart damage does occur, sophisticated treatments and surgical procedures often are necessary. Unfortunately, heart damage is typically irreversible, which is why researchers are seeking regenerative therapies that restore a damaged heart to its original capacity. We have known for hundreds of years that newts and other types of salamanders regenerate limbs. If you cut off a leg or tail, it will grow back within a few weeks. Stanley Sessions, a researcher at HartwichCollege in Oneonta, N.Y., wondered if this external phenomenon also took place internally. To find out, he surgically removed a piece of heart in more than two dozen newts. “To our surprise, if you surgically remove part of the heart, the creature will regenerate a new heart within just six weeks or so,” Sessions said. “In fact, you can remove up to half of the heart, and it will still regenerate completely!” Before the research team dove deeper into this finding, Sessions and his three undergraduate students, Grace Mele, Jessica Rodriquez and Kayla Murphy, had to determine how a salamander could even live with a partial heart. It turns out that a clot forms at the surgical site, acting much like the cork in a wine bottle, to prevent the amphibian from bleeding to death. What is the cork made of? In part, stem cells. Stem cells have unlimited potential for growth and can develop into cells with a specialized fate or function. Embryonic stem cells, for example, can give rise to all of the cells in the body and, thus, have promising potential for therapeutics.

As it turns out, stem cells play an important role in regeneration in newts. “We discovered that at least some of the stem cells for heart regeneration come from the blood, including the clot,” Sessions explained. This finding could have exciting implications for therapies in humans with heart damage. By finding the genes responsible for regeneration in the newt, researchers may be able to identify pathways that are similar in newts and people and could be used to induce regeneration in the human heart. In fact, a clinical trial performed just last year was the first to use stem-cell therapy to regenerate healthy tissue and repair a patient’s heart. Combining advances in medical and surgical technologies with the basic pathways of heart regeneration in newts could lead to better therapies for humans. Sessions posed this hopeful question: “Wouldn’t it be great if we could find a way to activate heart stem cells to bioengineer new heart tissue so that we can actually repair damaged hearts in humans?”

http://www.sciencedaily.com/  Science Daily

May 27, 2014

http://www.sciencedaily.com/releases/2014/04/140429184637.htm  Original web page at Science Daily

 

 

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Molecule critical to healing wounds identified

Skin provides a first line of defense against viruses, bacteria and parasites that might otherwise make people ill. When an injury breaks that barrier, a systematic chain of molecular signaling launches to close the wound and re-establish the skin’s layer of protection. A study led by researchers from the University of Pennsylvania’s School of Dental Medicine and published in the Journal of Cell Biology now offers a clearer explanation of the role of one of the players in the wound-healing process, a molecule called FOX01. Contrary to what had been expected, FOX01 is critical to wound healing, providing researchers with a possible new target for drugs that could help speed that process for people with impaired wound healing. Senior author Dana Graves is a professor in Penn Dental Medicine’s Department of Periodontics and is vice dean for scholarship and research. He collaborated on the study with Penn’s Bhaskar Ponugoti, Fanxing Xu, Chenying Zhang, Chen Tian and Sandra Pacio. A critical element of wound healing involves the movement of keratinocytes, the primary cells comprising the epidermis, or the outer layer of skin. Previous research had found that FOX01 was expressed at higher levels in wounds, but scientists did not understand what role the molecule was playing. In other scenarios, such as in cancer cells, FOX01 promotes cell death and interferes with the cell reproduction, two actions that would seem to be detrimental to healing.

To investigate the role of FOX01 in wound healing, Graves and colleagues bred mice that lacked the protein in their keratinocytes and then observed the wound healing process in these mice compared to mice with normal FOX01. “We thought that deleting FOX01 would speed up the wound-healing process,” Graves said, “but in fact it had the opposite effect.” The mice that lacked FOX01 showed significant delays in healing. Whereas all wounds on control mice were healed after one week, all of the experimental mice still had open wounds. Digging deeper into this counterintuitive finding, the researchers examined the effect of reducing FOX01 levels on other genes known to play a role in cell migration. They found that many of these genes were significantly reduced, notably TGF-β1, a critical growth factor in wound repair. When the team added TGF-β1 to cells lacking FOX01, the cells behaved normally and produced the proper suite of molecules needed for healing, indicating that FOX01 acts upstream of TGF-β1 in the signaling pathway triggered during the healing process. Further experimenting revealed that mice lacking FOX01 had evidence of increased oxidative stress, which is detrimental to wound healing. “The wound healing environment is a stressful environment for the cell,” Graves said. “It appears that upregulation of FOX01 helps protect the cell against oxidative stress.”

The fact that FOX01 behaves in this unexpected way could have to do with the specialized microenvironment of a cell in a wound, Graves noted. While FOX01 does indeed promote cell death when it is highly activated, it does the opposite when moderately activated. Which activity it promotes depends on the environment in which it is acting. Taken together, the study’s findings demonstrate that FOX01 plays an integral role in two key processes in wound healing: activation of TGF-β1 and protecting the cell against oxidative damage. Its involvement in these aspects of healing make it a potential target for pharmaceuticals that could help speed healing. “If you had a small molecule that increased FOX01 expression, you might be able to upregulate TGF-β1 as well as protect against the oxidative stress associated with wound healing,” Graves said.

Science Daily
December 10, 2013

Original web page at Science Daily

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Faster surgery may be better for hip fractures

The speed of surgery after a hip fracture may have a significant impact on outcomes for older patients, and faster may be better, say researchers at McMaster University. For seniors, hip fractures can cause serious complications that may result in death or admission to long-term care facilities for some people who previously lived at home. Hip fractures cause pain, bleeding and immobility and activate patient’s coagulation and stress systems which can lead to medical complications in people awaiting surgery. In many countries, including Canada, waits for hip surgery can be 24 hours or longer, mainly because of pre-surgery clearance procedures and lack of operating rooms. However, during the scientific study of 60 people aged 45 years or older in Canada and India, half received accelerated surgery within six hours and half had standard care of surgery 24 hours after diagnosis with a hip fracture. Among patients receiving standard care, 47% suffered a major complication of death, heart attack, stroke, pneumonia, blood clot or major bleeding event. However, only 30% of the patients in the accelerated surgery group suffered one of these complications. “We believe that the shortest time possible to treatment may provide the greatest potential for benefit, as is the case in acute heart attack and stroke,” said Dr. P.J. Devereaux, an associate professor of medicine and epidemiology at the Michael G. DeGroote School of Medicine at McMaster and co-principal investigator of the pilot trial. Dr. Mohit Bhandari, a professor of surgery of the McMaster medical school and co-principal investigator, added: “This pilot provides encouraging evidence that accelerated surgery may substantially improve outcomes in these patients.”

Science Daily
December 10, 2013

Original web page at Science Daily

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New ligament discovered‬ in the human knee

Two knee surgeons at University Hospitals Leuven have discovered a previously unknown ligament in the human knee. This ligament appears to play an important role in patients with anterior cruciate ligament (ACL) tears. ‪Despite a successful ACL repair surgery and rehabilitation, some patients with ACL-repaired knees continue to experience so-called ‘pivot shift’, or episodes where the knee ‘gives way’ during activity. For the last four years, orthopedic surgeons Dr Steven Claes and Professor Dr Johan Bellemans have been conducting research into serious ACL injuries in an effort to find out why. Their starting point: an 1879 article by a French surgeon that postulated the existence of an additional ligament located on the anterior of the human knee. That postulation turned out to be correct: the Belgian doctors are the first to identify the previously unknown ligament after a broad cadaver study using macroscopic dissection techniques. Their research shows that the ligament, which was given the name anterolateral ligament (ALL), is present in 97 per cent of all human knees. Subsequent research shows that pivot shift, the giving way of the knee in patients with an ACL tear, is caused by an injury in the ALL ligament. Some of the conclusions were recently published in the Journal of Anatomy. The Anatomical Society praised the research as “very refreshing” and commended the researchers for reminding the medical world that, despite the emergence of advanced technology, our knowledge of the basic anatomy of the human body is not yet exhaustive. ‪The research questions current medical thinking about serious ACL injuries and could signal a breakthrough in the treatment of patients with serious ACL injuries. Dr Claes and Professor Bellemans are currently working on a surgical technique to correct ALL injuries. Those results will be ready in several years.

Science Daily
November 26, 2013

Original web page at Science Daily

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Gene and stem cell therapy combination could aid wound healing

Johns Hopkins researchers, working with elderly mice, have determined that combining gene therapy with an extra boost of the same stem cells the body already uses to repair itself leads to faster healing of burns and greater blood flow to the site of the wound. Their findings offer insight into why older people with burns fail to heal as well as younger patients, and how to potentially harness the power of the body’s own bone marrow stem cells to reverse this age-related discrepancy. “As we get older, it is harder for our wounds to heal,” says John W. Harmon, M.D., a professor of surgery at the Johns Hopkins University School of Medicine, who will present his findings to the American College of Surgeons’ Surgical Biology Club on Sunday. “Our research suggests there may be a way to remedy that.” To heal burns or other wounds, stem cells from the bone marrow rush into action, homing to the wound where they can become blood vessels, skin and other reparative tissue. The migration and homing of the stem cells is organized by a protein called Hypoxia-Inducible Factor-1 (HIF-1). In older people, Harmon says, fewer of these stem cells are released from the bone marrow and there is a deficiency of HIF-1. The protein was first discovered about 15 years ago at Johns Hopkins by Gregg L. Semenza, M.D., Ph.D., one of Harmon’s collaborators.

Harmon and his colleagues first attempted to boost the healing process in mice with burn wounds by increasing levels of HIF-1 using gene therapy, a process that included injecting the rodents with a better working copy of the gene that codes for the protein. That had worked to improve healing of wounds in diabetic animals, but the burn wound is particularly difficult to heal, and that approach was insufficient. So they supplemented the gene therapy by removing bone marrow from a young mouse and growing out the needed stem cells in the lab. When they had enough, they injected those supercharged cells back into the mice. After 17 days, there were significantly more mice with completely healed burns in the group treated with the combination therapy than in the other groups, Harmon says. The animals that got the combination therapy also showed better blood flow and more blood vessels supplying the wounds. Harmon says a wound treatment like this that uses a patient’s own cells is promising because the patient would be less likely to reject them as they would cells from someone else. Meanwhile, he says, HIF-1 gene therapy has been safely used in humans with sudden lack of blood flow to a limb. “It’s not a stretch of the imagination to think this could someday be used in elderly people with burns or other difficult wounds,” Harmon says.

Johns Hopkins researchers from the Department of Plastic and Reconstructive Surgery report that a type of stem cell found easily in fat cells and also in bone marrow promoted nerve regeneration in rats with paralyzing leg injuries and in some of the rodents that received hind-leg transplants. The findings mark a step forward in understanding how mesenchymal stem cells (MSCs) may improve nerve regeneration after injury and limb transplant, while potentially minimizing the need for lifelong immunosuppression after reconstructive surgery to replace a lost limb, say study leaders W.P. Andrew Lee, M.D., and Gerald Brandacher, M.D. Such immunosuppressive drug therapy carries many unwanted side effects. “Mesenchymal stem cells may be a promising add-on therapy to help damaged nerves regenerate,” says John Pang, a medical student at the Johns Hopkins University School of Medicine, who is expected to present the findings on Wednesday. “We obviously need to learn much more, but we are encouraged by what we learned from these experiments.” MSCs most frequently become bone, cartilage and fat in the bodies of mammals, and researchers have been able to coax them in test tubes into becoming nerve cells and skin that lines blood vessels and tissue.

Notably, MSCs are not recognized by the body as foreign, making them less likely to trigger an immune system response or attack. Instead, these stem cells appear to secrete proteins that suppress the immune system in specific ways. Pang says it is those properties researchers hope to harness and use to not only regenerate nerve cells, but also to help transplant patients avoid immunosuppressant drugs. The Johns Hopkins team notes that harvesting MSCs is a relatively simple procedure, because accessible stores are found in body fat. They can also be extracted from bone marrow, a slightly more complicated process. The Johns Hopkins researchers experimented with three groups of rats: those whose femoral nerves were cut and repaired; those that received a hind-leg transplant from the same biological type of rat; and animals that received a transplant from a different type. Some rats had MSCs injected directly into the sciatic nerve, while others received them intravenously into the bloodstream. After 16 weeks, the researchers say the rats with severed and repaired nerves treated with MSCs showed significant improvements in nerve regrowth and nerve signaling. Those with transplants from similar rats appeared to also show benefit. The rats whose transplants came from dissimilar rodent types — the situation most similar to a human transplant from a cadaver — rejected their new limbs.

Science Daily
October 29, 2013

Original web page at Science Daily

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Fat grafting helps patients with scarring problems

Millions of people with scars suffer from pain, discomfort, and inability to perform regular activities. Some may have to revert to addicting pain medicine to get rid of their ailments. Now, and with a new methodology, such problems can be treated successfully. A technique using injection of the patient’s own fat cells is an effective treatment for hard, contracted scars resulting from burns or other causes, reports a study in the September issue of The Journal of Craniofacial Surgery, edited by Mutaz B. Habal, MD, FRCSC, and published by Lippincott Williams & Wilkins, a part of Wolters Kluwer Health. Dr. Marco Klinger and coauthors of Università degli Studi di Milano report good results with fat grafting in hundreds of patients with difficult-to-treat scars causing pain and limited motion. “For scar treatment, where medical and surgical therapies seem to be ineffective especially in the long term, autologous fat graft has proven to be a new chance to repair tissue damage,” the researchers write. “Fat Grafting Shows Promise as Treatment for Scars” Dr. Klinger and colleagues used autologous fat grafting to treat persistent scarring problems in nearly 700 patients over six years. (“autologous” means using the patient’s own tissues.) All patients had abnormal, painful scars causing hardening or tightening of the skin, often with limitation of motion. The scars — resulting from burns, surgery, or other causes — had not improved with other treatments.

The fat grafting procedure began with liposuction to collect a small amount of the patient’s own fat tissue — usually from the abdomen or hips. After processing, surgeons reinjected the fat cells under the skin in the area of scarring. Fat was distributed in different directions, with the goal of creating a “web” of support for scarred, damaged skin. Fat grafting led to significant improvement “both from an aesthetic and functional point of view,” according to Dr. Klinger and co-authors. The skin in the scarred area became “softer and more flexible and extensible, and very often color seemed similar to the surrounding unharmed skin.” After fat grafting, the patients had decreased pain and increased scar elasticity. Improvement began within two weeks, continued through three months, and persisted through one year and beyond. In a subgroup of patients, objective testing of skin hardness and clinical ratings by doctors and patients provided further evidence of treatment benefits. Fat cells lead to improved function as well as appearance. For example, in patients with scarring after burns to the face, fat grafting led to improved facial motion.

Fat grafting helped solve other difficult surgical problems as well. In one case, a breast cancer patient was left with hard, painful scars after complications from breast reconstruction. Treatment with fat grafting allowed a successful second breast reconstruction to be performed. In recent years, there has been renewed interest in techniques using the patient’s own fat for reconstructive and cosmetic plastic surgery. The new experience suggests that fat grafting may provide an effective new “regenerative medicine” technique for patients with difficult-to-treat scars. It’s not yet clear exactly how fat grafting exerts its benefits in scarred tissues. One factor may be the fact that fat tissue includes stem cells, which can develop into many different types of cells active in the wound healing and tissue repair process.

Science Daily
October 15, 2013

Original web page at Science Daily

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Glass scaffolds help heal bone, show promise as weight-bearing implants

Researchers at Missouri University of Science and Technology have developed a type of glass implant that could one day be used to repair injured bones in the arms, legs and other areas of the body that are most subject to the stresses of weight. This marks the first time researchers have shown a glass implant strong enough to bear weight can also integrate with bone and promote bone growth, says lead researcher Dr. Mohamed N. Rahaman, professor of materials science and engineering at Missouri S&T. In previous work, the Missouri S&T researchers developed a glass implant strong enough to handle the weight and pressure of repetitive movement, such as walking or lifting. In their most recent study, published in the journal Acta Biomaterialia, the research team reported that the glass implant, in the form of a porous scaffolding, also integrates with bone and promotes bone growth. This combination of strength and bone growth opens new possibilities for bone repair, says Rahaman, who also directs Missouri S&T’s Center for Biomedical Science and Engineering, where the research was conducted. “Right now, there is no synthetic material that is practical for structural bone repair,” Rahaman says.

Conventional approaches to structural bone repair involve either the use of a porous metal, which does not reliably heal bone, or a bone allograft from a cadaver. Both approaches are costly and carry risks, Rahaman says. He thinks the type of glass implant developed in his center could provide a more feasible approach for repairing injured bones. The glass is bioactive, which means that it reacts when implanted in living tissue and convert to a bone-like material. In their latest research, Rahaman and his colleagues implanted bioactive glass scaffolds into sections of the calvarial bones (skullcaps) of laboratory rats, then examined how well the glass integrated with the surrounding bone and how quickly new bone grew into the scaffold. The scaffolds are manufactured in Rahaman’s lab through a process known as robocasting — a computer-controlled technique to manufacture materials from ceramic slurries, layer by layer — to ensure uniform structure for the porous material. In previous studies by the Missouri S&T researchers, porous scaffolds of the silicate glass, known as 13-93, were found to have the same strength properties as cortical bone. Cortical bones are those outer bones of the body that bear the most weight and undergo the most repetitive stress. They include the long bones of the arms and legs. But what Rahaman and his colleagues didn’t know was how well the silicate 13-93 bioactive glass scaffolds would integrate with bone or how quickly bone would grow into the scaffolding.

“You can have the strongest material in the world, but it also must encourage bone growth in a reasonable amount of time,” says Rahaman. He considers three to six months to be a reasonable time frame for completely regenerating an injured bone into one strong enough to bear weight. In their studies, the S&T researchers found that the bioactive glass scaffolds bonded quickly to bone and promoted a significant amount of new bone growth within six weeks. While the skullcap is not a load-bearing bone, it is primarily a cortical bone. The purpose of this research was to demonstrate how well this type of glass scaffolding — already shown to be strong — would interact with cortical bone. Rahaman and his fellow researchers in the Center for Biomedical Science and Engineering are now experimenting with true load-bearing bones. They are now testing the silicate 13-93 implants in the femurs (leg bones) of laboratory rats. In the future, Rahaman plans to experiment with modified glass scaffolds to see how well they enhance certain attributes within bone. For instance, doping the glass with copper should promote the growth of blood vessels or capillaries within the new bone, while doping the glass with silver will give it antibacterial properties.

Science Daily
August 6, 2013

Original web page at Science Daily

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Baby’s life saved with groundbreaking 3-D printed tracheal splint that restored his airway

Every day, their baby stopped breathing, his collapsed bronchus blocking the crucial flow of air to his lungs. April and Bryan Gionfriddo watched helplessly, just praying that somehow the dire predictions weren’t true. “Quite a few doctors said he had a good chance of not leaving the hospital alive,” says April Gionfriddo, about her now 20-month-old son, Kaiba. “At that point, we were desperate. Anything that would work, we would take it and run with it.” They found hope at the University of Michigan, where a new, bioresorbable device that could help Kaiba was under development. Kaiba’s doctors contacted Glenn Green, M.D., associate professor of pediatric otolaryngology at the University of Michigan. Green and his colleague, Scott Hollister, Ph.D., professor of biomedical engineering and mechanical engineering and associate professor of surgery at U-M, went right into action, obtaining emergency clearance from the Food and Drug Administration to create and implant a tracheal splint for Kaiba made from a biopolymer called polycaprolactone.

On February 9, 2012, the specially-designed splint was placed in Kaiba at C.S. Mott Children’s Hospital. The splint was sewn around Kaiba’s airway to expand the bronchus and give it a skeleton to aid proper growth. Over about three years, the splint will be reabsorbed by the body. The case is featured today in the New England Journal of Medicine. “It was amazing. As soon as the splint was put in, the lungs started going up and down for the first time and we knew he was going to be OK,” says Green. Green and Hollister were able to make the custom-designed, custom-fabricated device using high-resolution imaging and computer-aided design. The device was created directly from a CT scan of Kaiba’s trachea/bronchus, integrating an image-based computer model with laser-based 3D printing to produce the splint. “Our vision at the University of Michigan Health System is to create the future of health care through discovery. This collaboration between faculty in our Medical School and College of Engineering is an incredible demonstration of how we achieve that vision, translating research into treatments for our patients,” says Ora Hirsch Pescovitz, M.D., U-M executive vice president for medical affairs and CEO of the U-M Health System.

“Groundbreaking discoveries that save lives of individuals across the nation and world are happening right here in Ann Arbor. I continue to be inspired and proud of the extraordinary people and the amazing work happening across the Health System.” Kaiba was off ventilator support 21 days after the procedure, and has not had breathing trouble since then. “The material we used is a nice choice for this. It takes about two to three years for the trachea to remodel and grow into a healthy state, and that’s about how long this material will take to dissolve into the body,” says Hollister. “Kaiba’s case is definitely the highlight of my career so far. To actually build something that a surgeon can use to save a person’s life? It’s a tremendous feeling.” The image-based design and 3D biomaterial printing process can be adapted to build and reconstruct a number of tissue structures. Green and Hollister have already utilized the process to build and test patient specific ear and nose structures in pre-clinical models. In addition, the method has been used by Hollister with collaborators to rebuild bone structures (spine, craniofacial and long bone) in pre-clinical models.

Severe tracheobronchomalacia is rare. About 1 in 2,200 babies are born with tracheomalacia and most children grow out of it by age 2 or 3, although it often is misdiagnosed as asthma that doesn’t respond to treatment. Severe cases, like Kaiba’s, are about 10 percent of that number. And they are frightening, says Green. A normal cold can cause a baby to stop breathing. In Kaiba’s case, the family was out at a restaurant when he was six weeks old and he turned blue. “Severe tracheobronchomalacia has been a condition that has bothered me for years,” says Green. “I’ve seen children die from it. To see this device work, it’s a major accomplishment and offers hope for these children.” Before the device was placed, Kaiba continued to stop breathing on a regular basis and required resuscitation daily. “Even with the best treatments available, he continued to have these episodes. He was imminently going to die. The physician treating him in Ohio knew there was no other option, other than our device in development here,” Green says. Kaiba is doing well and he and his family, including an older brother and sister, live in Ohio. “He has not had another episode of turning blue,” says April. “We are so thankful that something could be done for him. It means the world to us.”

Science Daily
June 11, 2013

Original web page at Science Daily

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Hundreds of tiny untethered surgical tools deployed in first animal biopsies

By using swarms of untethered grippers, each as small as a speck of dust, Johns Hopkins engineers and physicians say they have devised a new way to perform biopsies that could provide a more effective way to access narrow conduits in the body as well as find early signs of cancer or other diseases. In two recent peer-reviewed journal articles, the team reported successful animal testing of the tiny tools, which require no batteries, wires or tethers as they seize internal tissue samples. The devices are called “mu-grippers,” incorporating the Greek letter that represents the term for “micro.” Instead of relying on electric or pneumatic power, these star-shaped tools are autonomously activated by the body’s heat, which causes their tiny “fingers” to close on clusters of cells. Because the tools also contain a magnetic material, they can be retrieved through an existing body opening via a magnetic catheter. In the April print edition of Gastroenterology, the researchers described their use of the mu-grippers to collect cells from the colon and esophagus of a pig, which was selected because its intestinal tract is similar to that of humans. Earlier this year, the team members reported in the journal Advanced Materials that they had successfully inserted the mu-grippers through the mouth and stomach of a live animal and released them in a hard-to-access place, the bile duct, from which they obtained tissue samples.

“This is the first time that anyone has used a sub-millimeter-sized device — the size of a dust particle — to conduct a biopsy in a live animal,” said David Gracias, an associate professor of chemical and biomolecular engineering whose lab team developed the microgrippers. “That’s a significant accomplishment. And because we can send the grippers in through natural orifices, it is an important advance in minimally invasive treatment and a step toward the ultimate goal of making surgical procedures noninvasive.” Another member of the research team, physician Florin M. Selaru of the Johns Hopkins School of Medicine, said the mu-grippers could lead to an entirely new approach to conducting biopsies, which are considered the “gold standard” test for diagnosing cancer and other diseases. The advantage of the mu-grippers, he said, is that they could collect far more samples from many more locations. He pointed out that the much larger forceps used during a typical colonoscopy may remove 30 to 40 pieces of tissue to be studied for signs of cancer. But despite a doctor’s best intentions, the small number of specimens makes it easy to miss diseased lesions.

“What’s the likelihood of finding the needle in the haystack?” said Selaru, an assistant professor in the Division of Gastroenterology and Hepatology. “Based on a small sample, you can’t always draw accurate inferences. We need to be able to do a larger statistical sampling of the tissue. That’s what would give us enough statistical power to draw a conclusion, which, in essence, is what we’re trying to do with the microgrippers. We could deploy hundreds or even thousands of these grippers to get more samples and a better idea of what kind of or whether a disease is present.” Although each mu-gripper can grab a much smaller tissue sample than larger biopsy tools, the researchers said each gripper can retrieve enough cells for effective microscopic inspection and genetic analysis. Armed with this information, they said, the patient’s physician could be better prepared to diagnose and treat the patient. This approach would be possible through the latest application of the Gracias lab’s self-assembling tiny surgical tools, which can be activated by heat or chemicals, without relying on electrical wires, tubes, batteries or tethers. The low-cost devices are fabricated through photolithography, the same process used to make computer chips. Their fingerlike projections are made of materials that would normally curl inward, but the team adds a polymer resin to give the joints rigidity and to keep the digits from closing.

Prior to a biopsy, the grippers are kept on ice, so that the fingers remain in this extended position. An endoscopy tool then is used to insert hundreds of grippers into the area targeted for a biopsy. Within about five minutes, the warmth of the body causes the polymer coating to soften, and the fingers curl inward to grasp some tissue. A magnetic tool is then inserted to retrieve them. Although the animal testing results are promising, the researchers said the process will require further refinement before human testing can begin. “The next step is improving how we deploy the grippers,” Selaru said. “The concept is sound, but we still need to address some of the details. The other thing we need to do is thorough safety studies.” Further development can be costly, however. The team has applied for grants to fund advances in the project, which is protected by provisional patents obtained through the Johns Hopkins Technology Transfer Office. Biotechnology investors might also help move the project forward. “It is more a question of money than time as to how long it will take before we could use this in human patients,” Selaru said.

Science Daily
May 14, 2013

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Nasal lining used to breach blood/brain barrier

Neurodegenerative and central nervous system (CNS) diseases represent a major public health issue affecting at least 20 million children and adults in the United States alone. Multiple drugs exist to treat and potentially cure these debilitating diseases, but 98 percent of all potential pharmaceutical agents are prevented from reaching the CNS directly due to the blood-brain barrier. Using mucosa, or the lining of the nose, researchers in the department of Otology and Laryngology at the Massachusetts Eye and Ear/Harvard Medical School and the Biomedical Engineering Department of Boston University have demonstrated what may be the first known method to permanently bypass the blood-brain barrier, thus opening the door to new treatment options for those with neurodegenerative and CNS disease. Their study is published on PLOS ONE. Many attempts have been made to deliver drugs across the blood-brain barrier using methods such as osmotic disruption and implantation of catheters into the brain, however these methods are temporary and prone to infection and dislodgement. “As an endoscopic skull base surgeon, I and many other researchers have helped to develop methods to reconstruct large defects between the nose and brain using the patient’s own mucosa or nasal lining,” said Benjamin S. Bleier, M.D., Otolaryngologist at Mass. Eye and Ear and HMS Assistant Professor. Study co-author Xue Han, Ph.D., an assistant professor of Biomedical Engineering at Boston University, said, “The development of this model enables us to perform critical preclinical testing of novel therapies for neurological and psychiatric diseases.”

Inspired by recent advances in human endoscopic transnasal skull based surgical techniques, the investigators went to work to develop an animal model of this technique and use it to evaluate transmucosal permeability for the purpose of direct drug delivery to the brain. In this study using a mouse model, researchers describe a novel method of creating a semi-permeable window in the blood-brain barrier using purely autologous tissues to allow for higher molecular weight drug delivery to the CNS. They demonstrated for the first time that these membranes are capable of delivering molecules to the brain which are up to 1,000-times larger than those excluded by the blood-brain barrier. “Since this is a proven surgical technique which is known to be safe and well tolerated, this data suggests that these membranes may represent the first known method to permanently bypass the blood-brain barrier using the patient’s own tissue,” Dr. Bleier said. “This method may open the door for the development of a variety of new therapies for neurodegenerative and CNS disease.

Science Daily
May 14, 2013

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‘Sharps’ injuries have major health and cost impact for surgeons

Injuries caused by needles and other sharp instruments are a major occupational hazard for surgeons — with high costs related to the risk of contracting serious infectious diseases, according to a special article in the April issue of Plastic and Reconstructive Surgery, the official medical journal of the American Society of Plastic Surgeons (ASPS). ASPS Member Surgeon Dr. Kevin C. Chung and colleagues at The University of Michigan Health System, Ann Arbor, review the risks, health impact and costs of “sharps” injuries for surgeons and other operating room personnel. They write, “Increased attention to the health, economic, personal and social implications of these injuries is essential for appropriate management and future prevention.” Nearly 400,000 sharps injuries occur each year in the United States. About 25 percent of injured workers are surgeons — for whom the risk is highest in the operating room. “Despite healthcare policies designed to protect healthcare workers, injuries remain common,” Dr. Chung and colleagues write. Nearly all surgeons will sustain a sharps injury sometime during their career. Medical students and residents are also at high risk; fatigue and inexperience are important risk factors.

The main health concern of sharps injuries is the risk of acquiring a communicable disease from a patient. While HIV is the most-feared result, the risk of infection with hepatitis B virus is actually much higher. Sharps injuries can also have a major psychological impact on the injured person and his or her family — particularly during the time needed to confirm that the injured worker is free of infection, which may take several weeks or months. Once an injury occurs, there are standardized guidelines for post-exposure prevention, depending on whether the patient has any known transmissible infections. Recommendations include antiviral medications for healthcare workers exposed to HIV and hepatitis B or C virus — ideally starting within hours after the injury. As a result of the need for testing and treatment, sharps injuries have a major economic impact. Average costs for testing, follow-up and preventive treatment range from $375 for needlestick exposure from a patient with no known blood-borne illness, up to nearly $2,500 for injuries from a patient with known HIV.

Post-exposure prevention can only be executed if the injury is reported. One study found that 70 percent of surgeons “never or rarely” report sharps injuries. They may feel they “don’t have time” to report, or may misunderstand the risks involved. “Fortunately, the majority of sharps injuries are preventable,” Dr. Chung and colleagues write. Engineered safety devices can prevent many injuries — especially if surgeons and other workers are involved in choosing to use them. Other options include the use of “non-sharp” alternatives, creating safe procedures for passing sharp instruments and wearing double gloves to reduce the risk of infection. Over the years, regulations have been introduced to ensure that proper prevention and reporting strategies are in place. Introduction of the Needlestick Safety and Prevention Act of 2000 led to an overall 38 percent reduction in injuries in all care settings. However, one study reported that the rate of sharps injuries in the operating room actually increased. “Although preventive strategies exist, their success ultimately relies on clinician compliance,” Dr. Chung and coauthors write. The authors hope their review will help to increase awareness of the risks and potential harms of sharps injuries among surgeons and operating room personnel, and to increase awareness of efforts to reduce the risk. They conclude, “Targeting educational initiatives during medical school and training may improve knowledge among surgeons of the safest ways to practice in the operating room, and ensuring compliance among all surgeons in practice can reduce the economic and psychosocial burden of these highly prevalent injuries.”

Science Daily
April 16, 2013

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Fallout from nuclear testing shows that the Achilles tendon can’t heal itself

Notorious among athletes and trainers as career killers, Achilles tendon injuries are among the most devastating. Now, by carbon testing tissues exposed to nuclear fallout in post WWII tests, scientists have learned why: Like our teeth and the lenses in our eyes, the Achilles tendon is a tissue that does not repair itself. This discovery was published online in The FASEB Journal. “Tendon injury is a very common disease, which hinders many people from enjoying the numerous benefits of sports and recreational activities,” said Katja Heinemeier, Ph.D., a researcher involved in the work from the Institute of Sport Medicine and Center for Healthy Aging at the University of Copenhagen in Denmark. “We hope that these new results will provide the essential knowledge necessary for the development of effective treatments of tendon diseases.” Heinemeier and colleagues made this discovery by taking advantage of carbon-14 spikes resulting from post WWII nuclear bomb tests. Because of these tests, there was a large release of the radioactive carbon-14 (radiocarbon) to the atmosphere between 1955 and 1963. This sudden rise in carbon-14 — called the “bomb pulse” — reached a maximum of twice the natural atmospheric level in 1963, and then gradually dropped to the lower levels over time. This variation is reflected in all human tissue, because humans eat plants (and animals fed on plants) that take up carbon-14 from the atmosphere.

Researchers studied the Achilles tendons from people who had lived during the carbon-14 bomb pulse peak, and found that the high carbon-14 levels of this period had remained in the tendon tissue for decades after. This persistence of radiocarbon can only be explained by the fact that the rate of tissue renewal is extremely slow in the tendon, if it exists at all. In fact, the results showed that the Achilles tendon stays the same after growing ends. In comparison, muscle tissue from the same persons had been constantly renewed and contained no “memory” of the radiocarbon. “While the nation waits to see if another Olympic skier or NFL rookie recovers from serious tendon or ligament damage, this report serves as a cautionary tale to temper expectations,” said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. “When it comes to our tendons, what we have may be all we have. Like our teeth, it’s far better and less painful in the long term to protect them throughout your lifetime than it is to count on a successful recovery.”

Science Daily
March 5, 2013

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Stem cells boost heart’s natural repair mechanisms

Injecting specialized cardiac stem cells into a patient’s heart rebuilds healthy tissue after a heart attack, but where do the new cells come from and how are they transformed into functional muscle? Researchers at the Cedars-Sinai Heart Institute, whose clinical trial results in 2012 demonstrated that stem cell therapy reduces scarring and regenerates healthy tissue after a heart attack, now have found that the stem cell technique boosts production of existing adult heart cells (cardiomyocytes) and spurs recruitment of existing stem cells that mature into heart cells. The findings, from a laboratory animal study, are published in EMBO Molecular Medicine online. “We’re finding that the effect of stem cell therapy is indirect. It stimulates proliferation of dormant surviving host heart tissue, and it attracts stem cells already in the heart. The resultant new heart muscle is functional and durable, but the transplanted stem cells themselves do not last long,” said Eduardo Marbán, MD, PhD, director of the Heart Institute. Marbán, the article’s senior author, invented the experimental stem cell procedures and technology tested in humans.

Consistent with previous studies, the researchers found that the heart’s native stem cells are not responsible for the normal replenishment of lost heart cells, but they do contribute to rebuilding heart tissue after heart attack. This study shows that existing heart cells contribute to formation of new heart cells in the normal heart: Through a gradual cycling process, dying heart cells are replaced by new ones. The researchers found that this cycling process escalates in response to heart attack, enabling existing heart cells to assist in the development of new ones. Further, these effects can be amplified through stem cell therapy. The investigational therapy turns on genes that bolster cell production from both sources — existing heart cells and existing stem cells — essentially boosting the heart’s normal means of cell replacement and its natural responses to injury. The injection of stem cells also improves heart structure and function. Marbán and his clinical and research teams in 2009 performed the first procedure in which a heart attack patient’s own heart tissue was used to grow specialized stem cells that were injected back into the heart. Earlier this year, they reported results of a clinical trial that found significant reduction in the size of heart attack-caused scars in patients who underwent the experimental stem cell procedure, compared to others who did not.

Although the preliminary results are positive, the researchers do not know precisely how the research treatment works. “Understanding the cellular sources and mechanisms of heart regeneration is the first step toward refining our strategies to more effectively regenerate healthy tissue after heart attacks,” said Marbán, the Mark S. Siegel Family Professor. The animal study was supported by National Institutes of Health grant R01 HL083109, the California Institute for Regenerative Medicine and the Cedars-Sinai Board of Governors Heart Stem Cell Center. The process to grow cardiac-derived stem cells involved in the clinical trial was developed earlier by Marbán when he was on the faculty of Johns Hopkins University. The university has filed for a patent on that intellectual property and has licensed it to Capricor Inc., a biotechnology company in which Dr. Marbán is a founder and equity holder. The company provided no funding for this study.

Science Daily
February 19, 2013

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Stem cells found to heal damaged artery in lab study in baboons

Scientists at the Texas Biomedical Research Institute in San Antonio have for the first time demonstrated that baboon embryonic stem cells can be programmed to completely restore a severely damaged artery. These early results show promise for eventually developing stem cell therapies to restore human tissues or organs damaged by age or disease. “We first cultured the stem cells in petri dishes under special conditions to make them differentiate into cells that are the precursors of blood vessels, and we saw that we could get them to form tubular and branching structures, similar to blood vessels,” said John L. VandeBerg, Ph.D., Texas Biomed’s chief scientific officer. This finding gave VandeBerg and his team the confidence to do complex experiments to find out if these cells could actually heal a damaged artery. Human embryonic stem cells were first isolated and grown in 1998. The results are presented in a manuscript, co-authored by Texas Biomed’s Qiang Shi, Ph.D., and Gerald Shatten, Ph.D., of the University of Pittsburgh, published in the January 10, 2013 issue of the Journal of Cellular and Molecular Medicine.

The scientists found that cells derived from embryonic stem cells could actually repair experimentally damaged baboon arteries and “are promising therapeutic agents for repairing damaged vasculature of people,” according to the authors. Researchers completely removed the cells that line the inside surface from a segment of artery, and then put cells that had been derived from embryonic stem cells inside the artery. They then connected both ends of the arterial segment to plastic tubing inside a device called a bioreactor which is designed to grow cells and tissues. The scientists then pumped fluid through the artery under pressure as if blood were flowing through it. The outside of the artery was bathed in another fluid to sustain the cells located there. Three days later, the complex structure of the inner surface was beginning to regenerate, and by 14 days, the inside of the artery had been perfectly restored to its complex natural state. It went from a non-functional tube to a complex fully functional artery. “Just think of what this kind of treatment would mean to a patient who had just suffered a heart attack as a consequence of a damaged coronary artery. And this is the real potential of stem cell regenerative medicine — that is, a treatment with stem cells that regenerates a damaged or destroyed tissue or organ,” VandeBerg said.

To show that the artery couldn’t heal itself in the absence of stem cells, the researchers took a control arterial segment that also was stripped of the cells on its interior surface, but did not seed it with stem cells. No healing occurred. Stains for proteins that indicate functional characteristics showed that the healed artery had completely normal function and could do everything that a normal artery does in a healthy individual. “This is evidence that we can harness stem cells to treat the gravest of arterial injuries,” said VandeBerg. Eventually, scientists hope to be able to take a skin cell or a white blood cell or a cell from any other tissue in the body, and induce it to become just like an embryonic stem cell in its capacity to differentiate into any tissue or organ. “The vision of the future is, for example, for a patient with a pancreas damaged because of diabetes, doctors could take skin cells, induce them to become stem cells, and then grow a new pancreas that is just like the one before disease developed,” VandeBerg said.

Science Daily
February 5, 2013

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Gastric bypass surgery alters gut microbiota profile along the intestine

Research to be presented at the Annual Meeting of the Society for the Study of Ingestive Behavior (SSIB) finds that gastric bypass surgery induces changes in the gut microbiota and peptide release that are similar to those seen after treatment with prebiotics. Previous animal research demonstrated that ingestion of a high-fat diet produces weight gain and profoundly affects the gut microbiota composition, resulting in a greater abundance of one type of bacteria called Firmicutes, and a decrease in Bifidobacteria spp and Bacteroidetes. A similar pattern has also been found in obese humans. Feeding of prebiotics, substances that enhance the growth of beneficial bacteria, changes the composition and/or the activity of the gastrointestinal microbiota, to promote the release of gut peptides and to improve glucose and lipid metabolism in diet-induced obese and type 2 diabetic mice.

Roux-en-Y gastric bypass (RYGB) surgery is considered the most effective treatment of morbid obesity and diabetes. Recent studies reported substantial shifts in the composition of the gut microbiota towards lower concentrations of Firmicutes and increased Bacteroidetes in obese subjects after RYGB. Most of the human studies on gut microbiota have been carried out using fecal samples which may not accurately represent how RYGB surgery affects the gut microbiota profile along different parts of the intestine. Because RYGB may affect how nutrients are absorbed in different portions of the intestine, a new study conducted by researchers at the University of Zurich measured the bacterial composition and the amounts of different peptides that affect food intake along different intestinal segments after RYGB in rats. They found that 14 weeks after surgery, Bifidobacteria spp, and Bacteroides-Prevotella spp content were significantly increased in several portions of the intestine in RYGB rats compared to control animals. In fact, the changes in gut microbe populations after RGYB resembled those seen after treatment with prebiotics. Gut microbiota changes were also associated with altered production of gastrointestinal hormones known to control energy balance. The lead author on this study, Melania Osto, Ph.D. said “Our findings show that RYGB surgery leads to changes in gut microbiota that resemble those seen after treatment with prebiotics. The results of this study suggest that postsurgical gut microbiota modulations may influence gut peptide release and significantly contribute to the beneficial metabolic effects of RYGB surgery.”

Science Daily
July 24, 2012

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Brain researchers start mapping the Human ‘Connectome’

A research effort called the Human Connectome Project is seeking to explore, define, and map the functional connections of the human brain. An update on progress in and upcoming plans for the Human Connectome Project appears in the July issue of Neurosurgery, official journal of the Congress of Neurological Surgeons. Analogous to the Human Genome Project — which mapped the human genetic code — the Human Connectome Project seeks to map “the complete, point-to-point spatial connectivity of neural pathways in the brain,” according to Arthur W. Toga, PhD, and colleagues of David Geffen School of Medicine, University of California Los Angeles. They write, “For neuroscientists and the lay public alike, the ability to assess, measure, and explore this wealth of layered information concerning how the brain is wired is a much sought after prize.” The 100 billion neurons of the human nervous system interconnect to form a relatively small number of “functional neural networks” responsible for behavior and thought. However, even after more than a century of research, there is no comprehensive map of the connections of the human brain.

Historically, studies of the human brain function have employed a “modular” view — for example, “region X is responsible for function Y.” However, a more appropriate approach is to consider which network of two or more “connected or interacting” regions is involved in a given function. Until recently, it was not possible to view networks in the living brain. But newer magnetic resonance imaging (MRI) methods sensitive to water diffusion have made it possible to create detailed maps of the underlying white matter connections between different areas of the brain. This opens the way to new approaches to mapping the structural connectivity of the brain, and showing it in ways that correspond to the brain anatomy. Researchers are working out ways to analyze these data using sophisticated modeling approaches to represent the “nodes and connections” that make up the functional networks of the brain. Such efforts are in their infancy, but these network models are capturing not only the connectedness of brain networks, but also their capacity to process information. Preliminary studies have yielded tantalizing findings, such as a link between more efficient cortical networks and increased intelligence and differences in connectedness between the right and left hemispheres of the brain. “The HCP has recently generated considerable interest because of its potential to explore connectivity and its relationship with genetics and behavior,” Dr. Toga and coauthors write.

The project has far-reaching implications for a wide range of neurological and psychiatric diseases, such as autism, schizophrenia, and Alzheimer’s disease. “The similarities and differences that mark normal diversity will help us to understand variation among people and set the stage to chart genetic influences on typical brain development and decline in human disease,” according to the authors. Dr. Toga and colleagues are making their data available for download and analysis by other researchers on the project website. In the future, the data will be openly available for exploration by the public.

Science Daily
July 24, 2012

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Seeing inside tissue for no-cut surgeries: Researchers develop technique to focus light inside biological tissue

Imagine if doctors could perform surgery without ever having to cut through your skin. Or if they could diagnose cancer by seeing tumors inside the body with a procedure that is as simple as an ultrasound. Thanks to a technique developed by engineers at the California Institute of Technology (Caltech), all of that may be possible in the not-so-distant future. The new method enables researchers to focus light efficiently inside biological tissue. While the previous limit for how deep light could be focused was only about one millimeter, the Caltech team is now able to reach two and a half millimeters. And, in principle, their technique could focus light as much as a few inches into tissue. The technique is used much like a flashlight shining on the body’s interior, and may eventually provide researchers and doctors with a host of possible biomedical applications, such as a less invasive way of diagnosing and treating diseases. If you crank up the power of light, you might even be able to do away with a traditional scalpel. “It enables the possibilities of doing incision-less surgery,” says Changhuei Yang, a professor of electrical engineering and bioengineering at Caltech and a senior author on the new study. “By generating a tight laser-focus spot deep in tissue, we can potentially use that as a laser scalpel that leaves the skin unharmed.” Ying Min Wang, a graduate student in electrical engineering, and Benjamin Judkewitz, a postdoctoral scholar, are the lead authors on the paper, which was published in the June 26 issue of the journal Nature Communications.

The new work builds on a previous technique that Yang and his colleagues developed to see through a layer of biological tissue, which is opaque because it scatters light. In the previous work, the researchers shined light through the tissue and then recorded the resulting scattered light on a holographic plate. The recording contained all the information about how the light beam scattered, zigzagging through the tissue. By playing the recording in reverse, the researchers were able to essentially send the light back through to the other side of the tissue, retracing its path to the original source. In this way, they could send light through a layer of tissue without the blurring effect of scattering. But to make images of what is inside tissue — to get a picture of cells or molecules that are embedded inside, say, a muscle — the researchers would have to be able to focus a light beam into the tissue. “For biologists, it’s most important to know what’s happening inside the tissue,” Wang says.

To focus light into tissue, the researchers expanded on the recent work of Lihong Wang’s group at Washington University in St. Louis (WUSTL); they had developed a method to focus light using the high-frequency vibrations of ultrasound. The WUSTL group took advantage of two properties of ultrasound. First, the high-frequency sound waves are not scattered by tissue, which is why it is great for taking images of fetuses in utero. Second, ultrasonic vibrations interact with light in such a way that they shift the light’s frequency ever so slightly. As a result of this so-called acousto-optic effect, any light that has interacted with ultrasound changes into a slightly different color. In both the WUSTL and Caltech experiments, the teams focused ultrasound waves into a small region inside a tissue sample. They then shined light into the sample, which, in turn, scattered the light. Because of the acousto-optic effect, any of the scattered light that passes through the region with the focused ultrasound will change to a slightly different color. The researchers can pick out this color-shifted light and record it. By employing the same playback technique as in the earlier Caltech work, they then send the light back, having only the color-shifted bits retrace their path to the small region where the ultrasound was focused — which means that the light itself is focused on that area, allowing an image to be created. The researchers can control where they want to focus the light simply by moving the ultrasound focus.

The WUSTL experiment was limited, however, because only a very small amount of light could be focused. The Caltech engineers’ new method, on the other hand, allows them to fire a beam of light with as much power as they want — which is essential for potential applications. The team demonstrated how the new method could be used with fluorescence imaging — a powerful technique used in a wide range of biological and biomedical research. The researchers embedded a patch of gel with a fluorescent pattern that spelled out “CIT” inside a tissue sample. Then, they scanned the sample with focused light beams. The focused light hit and excited the fluorescent pattern, resulting in the glowing letters “CIT” emanating from inside the tissue. The team also demonstrated their technique by taking images of tumors tagged with fluorescent dyes. “This demonstration that we can focus significant optical power deep within tissues opens up significant possibilities in optical imaging,” Yang says. By tagging cells or molecules that are markers for disease with fluorescent dyes, doctors can use this technique to make diagnoses noninvasively, much as if they were doing an ultrasound procedure.

Doctors might also use this process to treat cancer with photodynamic therapy. In this procedure, a drug that contains light-sensitive, cancer-killing compounds is injected into a patient. Cancer cells absorb those compounds preferentially, so that the compounds kill the cells when light shines on them. Photodynamic therapy is now only used at tissue surfaces, because of the way light is easily scattered. The new technique should allow doctors to reach cancer cells deeper inside tissue. The team has been able to more than double the current limit for how far light can be focused into tissue. With future improvements on the optoelectronic hardware used to record and play back light, the engineers say, they may be able to reach 10 centimeters (almost 4 inches) — the depth limit of ultrasound — within a few years. Still, the researchers say, their demonstration shows they have overcome the main conceptual hurdle for effectively focusing light deep inside tissue. “This is a big breakthrough, and we’re excited about the potential,” Judkewitz says. Adds Caltech’s Wang, “It’s a very new way to image into tissue, which could lead to a lot of promising applications.”

Science Daily
July 10, 2012

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Laser scalpels get ultrafast, ultra-accurate, and ultra-compact makeover

Whether surgeons slice with a traditional scalpel or cut away with a surgical laser, most medical operations end up removing some healthy tissue, along with the bad. This means that for delicate areas like the brain, throat, and digestive tract, physicians and patients have to balance the benefits of treatment against possible collateral damage. To help shift this balance in the patient’s favor, a team of researchers from the University of Texas at Austin has developed a small, flexible endoscopic medical device fitted with a femtosecond laser “scalpel” that can remove diseased or damaged tissue while leaving healthy cells untouched. The researchers will present their work at this year’s Conference on Lasers and Electro Optics (CLEO: 2012) in San Jose, Calif., taking place May 6-11. The device, which was engineered with off-the-shelf parts, includes a laser capable of generating pulses of light a mere 200 quadrillionths of a second in duration. These bursts are powerful, but are so fleeting that they spare surrounding tissue. The laser is coupled with a mini-microscope that provides the precise control necessary for highly delicate surgery. Using an imaging technique known as “two-photon fluorescence,” this specialized microscope relies on infrared light that penetrates up to one millimeter into living tissue, which allows surgeons to target individual cells or even smaller parts such as cell nuclei. The entire endoscope probe package, which is thinner than a pencil and less than an inch long (9.6 millimeters in circumference and 23 millimeters long), can fit into large endoscopes, such as those used for colonoscopies.

“All the optics we tested can go into a real endoscope,” says Adela Ben-Yakar of the University of Texas at Austin, the project’s principal investigator. “The probe has proven that it’s functional and feasible and can be manufactured commercially.” The new system is five times smaller than the team’s first prototype and boosts the imaging resolution by 20 percent, says Ben-Yakar. The optics consist of three parts: commercial lenses; a specialized fiber to deliver the ultrashort laser pulses from the laser to the microscope; and a 750-micrometer MEMS (micro-electro-mechanical system) scanning mirror. To hold the optical components in alignment, the team designed a miniaturized case fabricated using 3-D printing, in which solid objects are created from a digital file by laying down successive layers of material. Tabletop femtosecond lasers are already in use for eye surgery, but Ben-Yakar sees many more applications inside the body. These include repairing the vocal cords or removing small tumors in the spinal cord or other tissues. Ben-Yakar’s group is currently collaborating on two projects: treating scarred vocal folds with a probe tailored for the larynx, and nanosurgery on brain neurons and synapses and cellular structures such as organelles. “We are developing the next-generation clinical tools for microsurgery,” says Ben-Yakar. The new design has so far been laboratory-tested on pig vocal chords and the tendons of rat tails, and an earlier prototype was laboratory-tested on human breast cancer cells. The system is ready to move into commercialization, says Ben-Yakar. However, the first viable laser scalpel based on the team’s device will still need at least five years of clinical testing before it receives FDA approval for human use, Ben-Yakar adds.

Science Daily
May 15, 2012

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Botox injections now used for severe urinary incontinence

When you think of Botox injections, you probably think of getting rid of unwanted wrinkles around the eyes or forehead, but recently the US Food and Drug Administration (FDA) approved using the injections to help patients with neurological conditions who suffer from incontinence, or an overactive bladder. Botox injections paralyze the bladder muscle to prevent contractions that cause urgency to urinate or leak. Although medications and behavioral modifications are treatment options, many patients, especially the elderly, do not respond to these methods and need a more aggressive approach. “About 80 percent of patients with neurological conditions, such as spinal cord injuries, Parkinson’s disease and multiple sclerosis, see improvement after about a week, and the results can last four to nine months,” said Charles Nager, MD, co-director of the UC San Diego Women’s Pelvic Medicine Center at UC San Diego Health System.

Incontinence is the seventh condition, including chronic migraines and underarm sweating, that Botox has been approved to treat since the drug first arrived on the market as a wrinkle reducer in 2002. The outpatient procedure uses a local numbing gel, followed by 15 to 20 injections in different areas of the bladder muscle. “It can really be life changing for someone with severe incontinence issues,” said Nager who also serves as director of Urogynecology and Reconstructive Pelvic Surgery in the Department of Reproductive Medicine at UC San Diego. UC San Diego Health System is currently recruiting for a clinical trial to test Botox injections versus sacral nerve stimulation as incontinence treatment options. Sacral nerve stimulation uses small, electrical impulses to the nerves that control urination. The impulses are generated by a small device surgically placed under the skin. Attached to the device is a thin, electrode-tipped wire that passes under the patient’s skin, carrying impulses to the sacral nerve. The surgery is an outpatient procedure done under local anesthesia. Patients involved in the clinical trial are required to have tried two drugs that previously failed to treat their incontinence issues.

Science Daily
April 3, 2012

Original web page at Science Daily