Urology

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 H. Gil Rushton, 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.

Michael Hsieh receives grant to explore parasite proteins for pain relief

Michael Hsieh

Michael Hsieh, M.D., hopes to use parasite proteins to alleviate pain in multiple types of bladder inflammation.

Children’s National Health System Urologist Michael Hsieh, M.D., was awarded a National Institutes of Health (NIH) grant to optimize a set of parasite proteins that could alleviate pain in multiple types of bladder inflammation.

The $1 million R01 grant will fund a five-year study to exploit a parasite-derived protein, IPSE, as a candidate therapeutic. Dr. Hsieh hypothesizes that IPSE may have the ability to modulate host immune and non-immune responses to bladder injury. IPSE could be optimized for therapeutic potential, while minimizing toxicity, by generating forms that have the ability to modulate host responses via three distinct mechanisms: IL-4-binding, chemokine-binding and nuclear localization.

Postdoctoral researcher receives Urology Care Foundation Research Scholar Award

Evaristus Mbanefo, Ph.D., M.S., M.Sc., a postdoctoral researcher at Children’s National Health System, was awarded the 2017 Urology Care Foundation Research Scholar Award in recognition of his potential for a successful career in urology research. Mbanefo’s project, “Therapeutic Exploitation of Interleukin-4-Inducing Principle from Schistosoma Mansoni Eggs: A Urogenital Parasite-Derived Host Immunomodulatory Protein for Hemorrhagic Cystitis and Bladder Hypersensitivity,” was among 70 applications for the highly competitive annual award. He works in the lab run by Michael H. Hsieh, M.D., Ph.D., Director of the Clinic for Adolescent and Adult Pediatric Onset Urology (CAPITUL) at Children’s National.

Research finalist: targeted ultrasound of the tibial nerve can affect bladder function

Daniel Casella, M.D,, wants to design a bracelet that uses ultrasound waves to stimulate the posterior tibial nerve in pediatric patients with overactive and underactive bladders. “Realistically and optimistically, we might be five years away from that,” says Dr. Casella, a pediatric urologist at Children’s National Health System who has been studying the ability of ultrasound mediated neuromodulation of the posterior tibial nerve to affect bladder function. For this work, he was named a research finalist at the Pediatric Urology Fall Congress in September.

Up to 40 percent of patients seen in a pediatric urology clinic have an element of voiding dysfunction. The majority of these patients can be managed with behavior modification and conservative measures; however there is a subset of these patients who will require more aggressive therapy. With the possibilities that this research holds, he suggests ultrasound mediated tibial nerve stimulation as potentially an ideal outpatient treatment of overactive bladder and dysfunctional elimination.

What we know

The S3 sacral nerve root contains neurons that play an important role in regulating bladder function. Stimulation of the S3 nerve root with a surgically placed neurostimulator is an effective treatment for overactive or underactive bladders in adults and more recently pediatric patients. The problem: Placement of the S3 nerve stimulator is an invasive surgical procedure that requires revision or additional procedures in up to 50 percent of pediatric patients.

Another treatment: Stimulation of the posterior tibial nerve (a peripheral extension of the S3 nerve root), with an electrical current is also an effective treatment of both overactive and underactive bladders. The problem: For a durable response, the posterior tibial nerve must be stimulated with an electrical current that produces a moderate level of discomfort for 30 minutes. These treatment sessions must then be repeated weekly for approximately 12 weeks, making it very difficult to offer this therapy to pediatric patients.

New hope for patients with bladder dysfunction

Using targeted ultrasound to stimulate nerves is an area of active research within the radiology and neuroscience community. To date, studies in humans are limited, however there have been promising results when transcranial ultrasound was used to stimulate the deep brain motor centers, potentially offering a novel treatment for movement disorders such as Parkinson’s.

Dr. Casella started this research during his pediatric fellowship at Vanderbilt with the support of a $25,000 grant from the Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction.

Dr. Casella says: “Using an established model of bladder overactivity in rats, we demonstrated that 2-3 minutes of ultrasound stimulation of the posterior tibial nerve can suppress bladder contractions for an average of 10 minutes.”

What’s next?

Dr. Casella plans to refine his techniques in animal models and work toward designing an ultrasound probe that can be used in humans. He is hopeful that his protocol will be ready for application in a clinical trial in the next one to two years. “Ultimately our goal is to design something that can be used at home,” Dr. Casella says. Ultrasound devices can be more compact if imaging isn’t the primary use. Ideally we would like to have the ultrasound transducer in the form of an ankle bracelet attached to a generator similar in size to a smartphone.

Urology research team wins best basic science award

Parasites have developed ingenious strategies to change their host’s biology. A research team led by Michael H. Hsieh, M.D., Ph.D., Director of the Clinic for Adolescent and Adult PedIatric OnseT UroLogy (CAPITUL) at Children’s National, turned the tables on the pesky parasites by using their proteins to provide therapeutic benefits. The team’s paper, “Therapeutic Exploitation of IPSE, a Urogenital Parasite-Derived Host Modulatory Protein, for Chemotherapy-Induced Hemorrhagic Cystitis and Bladder Hypersensitivity,” won the “Best Basic Science” award–a coveted national honor–during the Pediatric Urology Fall Congress in September. “Our work represents the first time that a uropathogen-derived host modulatory molecule has been therapeutically exploited in bladder disease models,” Dr. Hsieh and co-authors write.

Finding new ways to fight hemorrhagic cystitis for cancer patients

Michael Hsieh

Children diagnosed with cancer face fear and uncertainty, a series of medical appointments, and multiple diagnostic tests and treatments.

Children diagnosed with cancer face fear and uncertainty, a series of medical appointments, and multiple diagnostic tests and treatments. On top of these challenges, says Children’s National Health System urologist Michael Hsieh, M.D., Ph.D., many patients contend with additional issues: Treatment side effects, discomforts, and dangers that nearly eclipse that of the cancer itself. One of the most common side effects is hemorrhagic cystitis (HC), a problem marked by extreme inflammation in the bladder that can lead to tremendous pain and bleeding.

HC often results from administering two common chemotherapy drugs, cyclophosphamide and ifosfamide, used to treat a wide variety of pediatric cancers, including leukemias and cancers of the eye and nerves. In the United States alone, nearly 400,000 patients of all ages receive these drugs annually. Of these, up to 40 percent develop some form of HC, from symptomatic disease characterized by pain and bloody urine to cellular changes to the bladder detected by microscopic analysis.

“Having to deal with therapy complications makes the cancer ordeal so much worse for our patients,” says Dr. Hsieh, Director of the Clinic for Adolescent and Adult Pediatric Onset Urology at Children’s National. “Being able to eliminate this extremely detrimental side effect once and for all could have an enormous impact on patients at our hospital and around the world.”

Preventing complications with mesna

The severity of side effects from cyclophosphamide and ifosfamide can vary from mild and fleeting to bladder bleeding so extensive that patients require multiple transfusions and surgery to remove blood clots that can obstruct urinary release, says Dr. Hsieh, who frequently treats patients with this condition. But HC isn’t inevitable, he adds. A drug called mesna has the potential to prevent this complication when prescribed before a patient receives chemotherapy.

The problem is for a fraction of patients, mesna simply doesn’t work. For others, mesna can cause its own serious side effects, such as life-threatening malfunctions of the heart’s electrical system or allergic reactions.

“These kids are often already very sick from their cancers and treatments, and then you compound it with these complications,” says Dr. Hsieh. “There’s a desperate need for alternatives to mesna.”

Looking at alternative treatments

In a new review of the scientific literature, published August 24 by Urology, senior author Dr. Hsieh and a colleague detail all the substitutes for this drug that researchers have examined over several years.

One of these is hyperhydration, or delivering extra fluid intravenously to help flush the bladder and keep dangerous chemotherapy drug metabolites from accumulating and causing damage. Hyperhydration, however, isn’t an option for some patients with kidney, lung, or liver problems, who can’t tolerate excess fluid.

Researchers also have invested heavily in antioxidants as alternative treatments. Because much of the damage caused by these chemotherapy agents is thought to result from a cascade of oxidizing free radicals that cyclophosphamide and ifosfamide launch in the bladder, antioxidants might prevent injury by halting the free radical attack. Antioxidants that researchers have explored for this purpose include cytokines, or immune-signaling molecules, known as interleukin-1 and tumor necrosis factor, and a compound called reduced glutathione. Other studies have tested plant-based antioxidants, including a component of red wine known as resveratrol; a compound called diallyl disulfide isolated from garlic oil; and extracts from Uncaria tomentosa, a woody vine commonly known as “cat’s claw” that grows in the jungles of Central and South America.

Researchers also have tested options that focus on reducing the intense inflammation that cyclophosphamide and ifosfamide cause in the bladder, including the corticoid steroid drug dexamethasone as well as another cytokine known as interleukin-4.

However, Dr. Hsieh says, studies have shown that each of these treatments is inferior to mesna. To truly combat HC, researchers not only need to find new drugs and methods that outperform mesna but also new ways to reverse HC after other measures fail—problems he’s working to solve in his own lab.

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Cryopreservation of testicular tissue gives cancer patients fertility hope

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One of the most common causes of premature death is cancer. But today, survival rates for many childhood cancers have surpassed 90 percent and the emphasis of care has shifted from survival to quality of life after survival. That’s according to Michael Hsieh, M.D., Ph.D., who is leading the program at Children’s National Health System and getting much support from oncology and neonatology.

“One of the important aspects of quality of life is fertility,” Dr. Hsieh says. “For those adult survivors of childhood cancer who want to have children, I think it’s imperative that we do whatever we can to help them.”

The program at Children’s National, part of a multi-institutional consortium based at the University of Pittsburgh, had one of the highest recruitment of all the satellite sites for this study, which offers cryopreservation of boys’ testicular tissue. From Dr. Hsieh’s program, tissue from 11 patients has been harvested in a year and a half.

Radiation and chemotherapy are toxic to the gonads, which have testicular and ovarian function. “The idea is that if we can freeze the testicular tissue until the technology catches up in such that we can restore fertility down the road, that’s a wonderful thing. Most of these children are in grade school and not interested in having children until at least 15-20 years.”

Getting the tissue samples

For the first time, parents of young cancer patients are having this discussion, and Hsieh says they are extremely appreciative, even if they decline to participate in the study.

Young men can provide a sperm sample, which can easily be frozen. For boys who haven’t gone through puberty or boys who are not able to give a sample because they are too sick or unwilling to do so, a biopsy can collect a tissue sample, which can then be frozen.

Storing samples at a cost

Hsieh says his work also is focused on improving funding for storage of tissues. The out-of-pocket costs to store samples are several hundred dollars a year, and it can be cost-prohibitive for some patients and families.

Hsieh has applied for financial assistance from Children’s National internal funding opportunities for the program to help even the playing field.

“I don’t think it’s fair that a child who is born into a poor family is unable to participate in fertility preservation whereas a child who happens to be born more affluent is able to,” Hsieh says.

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.