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Matt Oetgen talks about an x-ray

Nicotine-like anti-inflammatories may protect limbs, testicles from inflammatory damage after injury

Matt Oetgen talks about an x-ray

Dr. Matt Oetgen is teaming up with pediatric urologist Dan Casella for a POSNA-funded pre-clinical study of the anti-inflammatories varenicline and cytisine.

A new pre-clinical study will explore the use of anti-inflammatory medications to prevent the body’s inflammatory response from further damaging limbs after an injury restricts blood flow. Varenicline and cytisine, anti-inflammatories with similarities to nicotine, have shown early promise in similar pre-clinical laboratory studies of the testicles and will now be tested in arms and legs.

Matthew Oetgen, M.D., MBA, chief of Orthopaedic Surgery and Sports Medicine at Children’s National and Children’s pediatric urologist Daniel Casella, M.D., will jointly lead the new study entitled, “Modulation of the Injury Associated with Acute Compartment Syndrome,” which builds on Dr. Casella’s previous work with the two anti-inflammatory agents. Drs. Oetgen and Casella recently were awarded the Angela S.M. Kuo Memorial Award Research Grant to fund this research during the Pediatric Orthopaedic Society of North America’s (POSNA) Annual Meeting.

“We are honored that this important research was selected by POSNA for support,” says Dr. Oetgen. “An arm or leg injury can trigger the body’s natural inflammatory response, causing severe swelling that restricts blood flow. Even after blood flow is restored, the inflammatory response can lead to permanent muscle or nerve damage or even loss of limb. This grant will give us the opportunity to truly explore the application of anti-inflammatories after injury and see if this approach can modulate the immune response to protect the limbs.”

If successful in the laboratory, the team hopes to expand this work to human clinical trials.

The Angela S.M. Kuo Memorial Award Research Grant is given each year to an outstanding investigator aged 45 or younger based on criteria including the study’s potential significance, impact, originality/innovation, the investigator’s track record and study feasibility. The award totals $30,000.

While at POSNA’s 2019 Annual Meeting, Dr. Oetgen and Children’s pediatric orthopaedic surgery colleagues also participated in podium presentations and poster sessions, including:

  • “Achieving Consensus on the Treatment of Pediatric Femoral Shaft Fractures,” Matthew Oetgen, M.D., MBA
  • “A Prospective, Multi-centered Comparative Study of Non-operative and Operative Containment Treatments in Children Presenting with Late-stage Legg-Calve-Perthes Disease,” Benjamin Martin, M.D.

The Pediatric Orthopaedic Society of North America is an organization of 1,400 surgeons, physicians, and allied health members dedicated to advancing musculoskeletal care for children and adolescents. The annual meeting presents the latest research and expert clinical opinion in pediatric orthopaedics through presentations, posters, and symposia. It was held May 15-18, 2019, in Charlotte, North Carolina.

Staphylococcus

How our bladder’s microbiota affect health

Staphylococcus

The presence of bacteria such as Staphylococcus in the urine is linked to the incidence and severity of urge urinary incontinence as well as treatment success.

About half of the cells in our bodies aren’t really “ours” at all. They’re the microbiota: The vast array of microorganisms that live in our gut, skin, oral cavity and other places. Decades ago, researchers thought that these organisms simply happened to colonize these areas, playing only a tangential role in health, for example, helping to break down food in the intestines or causing cavities. More recent work has revealed the incredibly complex role they play in diseases ranging from diabetes and schizophrenia.

The bladder is no exception. Just a single decade ago, the bladder was thought to be a sterile environment. But that view has shifted radically, with more sensitive cultivation methods and precise 16S rRNA gene-sequencing techniques revealing a significant bladder microbiome that could have an enormous impact on pediatric urologic diseases. These findings have opened brand new fields of research aimed at clarifying the role that the bladder’s microbiome plays in common urological diseases that affect children, according to a review article published online Feb. 22, 2018, by Current Urology Reports.

“There is a growing appreciation for the role of diverse bacteria in contributing to improved health as well as triggering disease processes or exacerbating illness,” says Michael H. Hsieh, M.D., Ph.D., director of the Clinic for Adolescent and Adult Pediatric Onset Urology (CAPITUL) at Children’s National Health System and study senior author. “Already, we know that probiotics and dietary modifications have the potential to play powerful roles in preventing urinary diseases that commonly occur among pediatric patients,” Dr. Hsieh says. This underscores the importance of conducting even more studies to improve our understanding and to identify new therapies for health conditions that resist current treatment options.”

The review conducted by Dr. Hsieh and co-authors highlights the effects of the microbiome on a number of urologic diseases that affect children, including:

  • Urinary tract infection A number of studies point to the association between decreased microbial diversity and the incidence of what is commonly called urinary tract infection (UTI) or “dysbiosis.” This relationship suggests that using probiotics to replace or supplement antibiotics could favorably alter the urinary microbiome. Future research will focus on the pathophysiological role of the microbiome to determine whether it can be manipulated to prevent or treat UTIs.
  • Urge urinary incontinence While data vary by study, the presence of bacteria in the urine, especially certain bacterial species – such as Gardnerella, Staphylococcus, Streptococcus, Actinomyces, Aerococcus, Corynebacterium and Oligella – are linked to the incidence and severity of urge urinary incontinence (UUI) as well as treatment success. Most studies find an association between greater genitourinary biodiversity and reduced incidence and lessened severity of UUI as well as improved treatment response. Future research will focus on further clarifying this relationship.
  • Urolithiasis Calcium oxalate stones, the most common type of kidney stone, have a microbiome that differs from the urinary microbiome leading researchers to question whether the stone’s own bacterial makeup could help to predict recurrence of future kidney stones. What’s more, Oxalobacter formigenes, a gram-negative bacterium, lowers oxalate levels in the blood and are associated with a 70 percent reduction in the risk of kidney stones forming. In an experimental model, fecal transplants with the full microbiome represented had a pronounced and persistent effect on oxalate production. Patients who receive some antibiotics often have reduced rates of formigenes colonization. However, the bacteria are resistant to amoxicillin, augmentin, ceftriaxone and vancomycin, which could point to preferential use of these antibiotics to stave off disease and ward off kidney stone formation.

Additional authors include Daniel Gerber, study lead author, The Georgetown University School of Medicine and Health Sciences; and Catherine Forster, M.D., study co-author, Children’s National.

Twitter Pediatric Urology Journal Club @pedurojc

Journal club, with a 140-character limit

Twitter Pediatric Urology Journal Club @pedurojc

@perforin & @chrbayne have launched a new journal club focused on pediatric urology via Twitter, a platform that democratizes and distills the academic discussion.

Journal club is a rite of passage for nearly everyone who works in an academic laboratory. What might sound like an exclusive group of readers and authors united by a secret handshake is actually a regular meeting of scientists – faculty members and young trainees alike – who gather to discuss a highlighted paper in their field of expertise.

Some of these gatherings might involve a handful of people from the same lab; others might include a larger group from the same institutional department or division. Typically, one person presents a paper, sharing all the relevant details about a study’s methodology and conclusions. Afterward, everyone has the chance to pose questions, make comments and thoroughly discuss conclusions.

“It’s an excellent academic opportunity in terms of teaching and training of early career scientists and clinicians, and it remains useful no matter what stage you are in your career,” says Michael Hsieh, M.D., Ph.D., a urologist who directs the Clinic for Adolescent and Adult PedIatric OnseT UroLogy (CAPITUL) at Children’s National Health System who has participated in a heavy share of journal club meetings over the years.

But, what if journal club didn’t have to adhere to this traditional format? What if this academic discussion could move to a venue more fitting for the 21st century, more inclusive of scientists in different geographic locations, with varying viewpoints and expertise?

That’s what Dr. Hsieh and others are trying to accomplish with a new pediatric urology-focused journal club on Twitter. When Christopher Bayne, a second-year fellow training in pediatric urology at Children’s National under Dr. Hsieh’s mentorship, approached him with the idea, Dr. Hsieh said that he jumped at the chance.

Traditional journal clubs, the two explain, can be hindered by several factors. One is a tendency toward “group think,” Dr. Hsieh says – members of the same lab, or even the same institution, tend to have the same training and practices, so they’re less likely to feel comfortable introducing new ideas about these areas into the discussion. Journal club discussions also are limited by uncertainties about what a study author might have had in mind with their methodology and conclusions. Study authors are rarely included in the discussion, Dr. Hsieh adds.

Michael Hsieh

“It’s an excellent academic opportunity in terms of teaching and training of early career scientists and clinicians, and it remains useful no matter what stage you are in your career,” says Michael Hsieh, M.D., Ph.D., a urologist who directs the Clinic for Adolescent and Adult PedIatric OnseT UroLogy (CAPITUL) at Children’s National Health System.

Twitter, Bayne says, offers an easy way around these barriers. Rather than including just members of the same lab, their Pediatric Urology Journal Club (PUJC) can accommodate any registered Twitter user in their discussions. That means that any interested person around the world – researchers, clinician-scientists, other health care providers, as well as patients and their families, for example – can participate in the monthly discussions.

Participation also isn’t dictated by geography. During recent PUJC meetings, individuals joined the thread from Brazil, Ireland and Turkey. The meetings, sponsored by the Journal of Pediatric Urology, take place in the first days to weeks after the selected paper has been available under “open access,” giving anyone a chance to read it – even if they lack a journal subscription. This format enables all participants to join threads, erasing the restrictions of geography or busy clinical and research schedules.

Thus far, the meetings have included papers on:

  • A comparison of the cost and complications of performing a surgery either robotically or through an open procedure to fix the tubes that connect the kidneys to the bladder in patients with a condition known as vesicouretal reflux, in which urine flows in the wrong direction.
  • The pros and cons of treating varicoceles, enlarged veins inside the scrotum that potentially cause fertility problems. The condition is asymptomatic in adolescents.
  • The importance of the diameter of the ureter, the part of the tube closest to the outside of the body that carries urine to be expelled, for resolving vesicouretal reflux, an abnormal flow of urine.

This new platform has attracted a core group of relatively young and young-at-heart devotees, Bayne says. He and other organizers have included study authors in every meeting thus far, often guiding older and Twitter-naive scientists through the process of creating an account.

And the typical 140-character limit Twitter imposes on comments known as tweets? “It might be counterintuitive,” Bayne says, “but I see the character limit as one of this journal club’s biggest strengths.” This cutoff encourages discussion members to distill their thoughts, often including two or three distinct points, into concise and deeply meaningful statements. “Participants have really latched on to the efficiency of this approach to learning about a topic and having a lively discussion.”

Thus far, their approach has been increasing in popularity. Their very first PUJC meeting in February 2017 attracted a modest number of just 24 active participants who sent 310 tweets, but generated nearly 136,000 impressions, or views.

The researchers plan to continue the monthly PUJC meetings through the Twitter handle @pedurojc. You can follow updates from Dr. Hsieh on his handle: @perforin and updates from Bayne’s on his: @chrbayne.

Boy and Mom with Doctor

Straightening out testicular torsion care

Boy and Mom with Doctor

A new collaborative accelerated care pathway for testicular torsion assessment and treatment may save critical time between diagnosis and intervention.

The clock starts ticking for a child with testicular torsion as soon as the pain starts. To increase the likelihood of successfully salvaging the twisted testicle and spermatic cord, surgical intervention – which involves restoring blood flow to the testis – should ideally occur within six hours from the onset of pain.

That’s six hours for a parent to identify that there is a problem, bring a child to the emergency department (ED) and go through all the steps required to get the child to the operating room. This process starts with an emergency physician, who probably doesn’t see many cases of this relatively rare condition, being able to identify the potential issue and contact the pediatric urologist on call. Next, diagnostic imaging orders need to be placed and actual imaging needs to occur for the diagnosis to be made. Finally, the patient needs to be moved to the pre-operative area, assessed by the anesthesia team and then taken to surgery.

In April 2016, the Division of Urology at Children’s National launched a new, accelerated care pathway for testicular torsion assessment and treatment that was developed collaboratively with the Emergency Department, Diagnostic Imaging and Radiology, the Department of Anesthesiology, and the peri-operative and operating room team.

“What stood out to us when we looked at the total time from identifying the problem to getting to surgery, was the length of time from when the diagnosis was made in the emergency department to the operating room,” says Tanya Davis, M.D., a pediatric urologist who led this new initiative along with Harry Rushton, Jr., M.D., chief of the Division of Urology. “It was an area where we could easily identify and streamline the process to accelerate the time for a patient to get from arrival in the ED to the surgical suite.”

Now, when a patient presents in the emergency department with the symptoms of testicular torsion, there is a straightforward path mapped out for the physician. “Who you need to talk to, how to reach them, relevant phone numbers, details on when to communicate to the attending physician, the ideal order of activities, the ability for residents to quickly transport the patient rather than waiting for hospital transport to surgery, and, most important, making it clear to everyone involved that this condition is a true emergency when every second matters,” Dr. Davis adds.

Torsion ED to OR Graph

Analysis of the streamlined care pathway, which emphasizes communication that the condition is a true emergency, has improved time from ED to OR within target ranges.

Since the initiative’s launch, 21 cases, from referrals and direct diagnosis, have come into the ED. The new protocol is working efficiently, reducing the mean time from the ED to the OR by more than an hour, now averaging below the team’s target goal of less than 2.5 hours from ED arrival to the OR.

Though salvage rates have not improved yet, the team will continue to collect data and monitor the impact of the accelerated pathway. Additionally, Dr. Davis says that a significant need remains for referring emergency and primary care physicians, as well as parents, to understand the condition and its need for urgent treatment. Children’s National urologists are developing handouts for both physicians and families to help raise awareness.

The hope is that more general knowledge of testicular torsion will allow parents, primary care doctors and emergency department staff to expedite diagnosis when a child complains of scrotal pain or has visible discoloration, further reducing the time from onset of pain to successful intervention. With such a short window of time for treatment, the accelerated care pathway is showing promising results.

bridge

Transitional urology bridges care for those with pediatric-onset conditions

bridging

A hot topic at national urology meetings is how to transition patients with pediatric-onset urologic conditions as they grow into adults. Michael Hsieh, MD, PhD, is leading the way in the U.S. by serving as a bridge for patients at the first dedicated transitional urology program in the mid-Atlantic region. The Clinic for Adolescent and Adult PedIatric OnseT UroLogy (CAPITUL) is a joint venture between Children’s National and George Washington University Hospital that started two years ago.

What’s most unique about the clinic is that Dr. Hsieh has a foot in both the pediatric world of urology and one in the adult world, with clinical privileges at both institutions. He sees the full span of pediatric urology patients, including expectant moms with fetuses that have suspected urologic anomalies to adults who may have congenital conditions that require follow-up. However, he sees more teenagers and young adults than his urology colleagues both at hospitals.

The clinic’s patients have included a 19-year-old man with multiple urethrocutaneous fistulas after failed hypospadias repairs, a 25-year-old woman with cloacal exstrophy and continent urinary diversion with a urinary tract infection and stones, and a 25-year-old man with spina bifida with incontinence urethral erosion from an indwelling catheter.

A number of significant urological conditions until recently led to premature death because of medical complications, Dr. Hsieh says. Today, 90 percent of spina bifida patients live past the age of 30. “There’s a synchronized wave of patients who are all now young adults with spina bifida, and they are facing issues of reproduction and sexuality,” Dr. Hsieh says. “These are issues that pediatric urologists generally speaking are not comfortable in managing. It makes sense: It’s been many, many years since they did that type of urology.”

The program is specifically following this transitional group on conditions that are long term and that may affect fertility, such as cancer and varicoceles.

One in five teenage boys have varicoceles, or varicose veins on the scrotum. “The relationship between having varicocele as a teenager and infertility as an adult is not clear, so we felt it important to include this diagnosis in the transitional program so we can follow these patients long term and monitor their testicular growth,” Dr. Hsieh says.

Proof that the program’s working

Dr. Hsieh tracks the messages from colleagues referring patients from one institution to the other. “Unfortunately, some patients and families—for a range of issues—fall through the cracks, so it is really important to have that direct link. If we didn’t have the program set up as it is, there would be fewer successful transitions between institutions,” he says.

Another way Dr. Hsieh knows the program is working is because of the uptick in adolescent and young adult patients in his practices at Children’s and at GW.

Dr. Hsieh says the optimal time to begin transition is at age 12, when the team makes the patient and family aware of the transition policy. From ages 14-16, it’s time to initiate the health care transition plan and begin discussing the adult model of care. By age 18, Dr. Hsieh recommends the transition to adult care, and by ages 23-26, patients are integrated into adult care.