Urology

surgeon doing laparoscopic surgery

Autonomous robotic laparoscopic surgery for intestinal anastomosis

surgeon doing laparoscopic surgery

Children’s National Hospital in collaboration with the University of North Carolina Wilmington and Johns Hopkins University developed an enhanced autonomous strategy for laparoscopic soft tissue surgery.

A new approach to soft tissue surgery could simplify autonomous surgical planning and enable collaborative surgery between an autonomous robot and human, a new study published in Science Robotics finds. This is the first time a robot can complete an autonomous soft tissue surgical task under laparoscopic conditions, forming the foundation for future soft tissue surgeries.

Children’s National Hospital in collaboration with the University of North Carolina Wilmington and Johns Hopkins University developed an enhanced autonomous strategy for laparoscopic soft tissue surgery. The multi-institutional effort made it possible to perform a robotic laparoscopic small bowel anastomosis in phantom and in vivo intestinal tissues. The findings further suggest that autonomous robot-assisted surgery has the potential to provide more efficacy, safety and consistency independent of an individual surgeon’s skill and experience.

The hold-up in the field

Autonomous anastomosis is known to be a challenging soft tissue surgery task. And in the laparoscopic setting, surgeries like these prove to be more challenging because of the need for high maneuverability and repeatability under motion and vision constraints – especially in pediatric patients.

“This work represents the first time autonomous soft tissue surgery has been performed using a laparoscopic technique and is the first step in bridging the gap between human and machine towards completing autonomous surgical tasks in soft tissue surgeries,” says Hamed Saeidi, Ph.D., assistant professor at University of North Carolina Wilmington and lead author of the study.

To overcome the unpredictable motions of the tissue, the experts used machine learning based techniques to track the dynamic motions of the soft tissue during the surgery. These methods also pave the way for markerless methods for tracking the tissue motion in future surgeries.

“Until now, laparoscopic autonomous surgeries were not possible in soft tissue due to the unpredictable motions of the tissue and limitations on the size and capabilities of surgical tools,” says Justin Opfermann, M.S., Ph.D., student and Johns Hopkins University and co-author.

What’s unique

Performing autonomous surgery would require the development of novel suturing tools, imaging systems and robotic controls to visualize a surgical scene, generate an optimized surgical plan and then execute that surgical plan with the highest precision.

The autonomous robot takes its skill one step further when performing surgical tasks on soft tissues by enabling a robot-human collaboration to complete more complicated surgical tasks where preoperative planning is not possible.

Additionally, the robot used in this work uses a novel shared control scheme called “conditional autonomy,” whereby the robot performs the majority of the surgical task, which the surgeon oversees.

Bottom line

“Combining all of these features into a single system is non-trivial,” Opfermann adds. “In 2016, we were the first group to demonstrate feasibility of semi-autonomous small bowel anastomosis with a robot in soft tissue, and now we can perform autonomous laparoscopic anastomosis.”

The resulting anastomosis had more consistency and achieved higher burst strength than surgeons suturing with manual technique, resulting in less anastomotic leak.

In laparoscopic surgeries – and pediatric patients especially – these challenges are even more difficult due to the small size of the patient. Robotic anastomosis is one way to ensure that surgical tasks that require high precision and repeatability can be performed with more accuracy and precision in every patient independent of surgeon skill.

“As a surgeon, I can attest to the potential benefits of improving how we perform surgery on our patients,” says Michael Hsieh, M.D., Ph.D., director of Transitional Urology at Children’s National Hospital. “Working with my engineering colleagues at Johns Hopkins, we’ve been able to develop prototypes of supervised, autonomous suturing robots that may be a step towards such improvements.”

Hans Pohl

Q&A with Hans Pohl, M.D., on the future of pediatric urology

Hans Pohl

Hans Pohl, Division Chief, Urology

The Urology team at Children’s National Hospital is led by Hans Pohl, M.D., and includes seven other fellowship-trained pediatric urologists and three nurse practitioners. Dr. Pohl has experience in treating patients with spina bifida and bladder exstrophy, in addition to the other more common diagnoses and in using laparoscopy to perform surgery through minimally invasive techniques.

Here, Dr. Pohl tells us more about the department he is leading and what it means for the future of pediatric urology patients at Children’s National.

What excites you most about current research in the field of urology?

The most cutting-edge research these days pertains to understanding the complex and diverse role played by bacteria in the urinary tract. We previously thought the urinary tract is sterile but that turns out to not be the case. Just like the friendly bacteria living in our bodies, there are bacteria that live within our urinary tracts. It is thought that when the normal function of the urinary tract is disrupted, the balance of healthy to unhealthy bacteria is disrupted. Our faculty at the Children’s National Urology Division are looking at urinary tract infection (UTI) from various aspects. Michael Hsieh, M.D., is investigating the role of bacteria in causing inflammation; Daniel Casella, M.D., has investigated how a drug called varenicline might reduce inflammation in infected kidneys; and Briony Varda, M.D., will be investigating the socioeconomic factors affecting how people living with spina bifida manage their urinary tracts and UTIs. By looking at UTIs at all levels from bacteria factors to host factors to treatment we will understand better how to reduce the impact of a very common problem on human beings.

What are some of the most valuable changes or advancements for the program you hope to see in the next couple of years?

I believe that our next step in program evolution will focus on improving the quality of life of children with urination abnormalities and UTIs. Everyone has experienced that their child has urinary symptoms at some point during childhood, some also have UTIs. Pediatric urologists have learned that normal lower urinary tract function is critically important in reducing a child’s risk for a UTI. Even if a child does not have UTIs, there can be significant social stigma amongst a child’s peers when loss of urine control happens.

What makes the Urology Division at Children’s National unique from other programs in the country?

We have grown considerably over the past several years, adding to our faculty surgeons with complimentary skills outside of the operating room. For instance, we have pediatric urologists who are also basic scientists, translational scientists, systems scientists, a clinical informaticist and minimally invasive surgeons. These varied qualities create a dynamic group of people who bring diverse perspectives to treating patients’ problems and generating creative solutions. We believe that our democratic process of complex care management where all surgeons can openly think about how to optimize patient management is unique. Patients don’t get one opinion from their surgeon, they get ten.

two doctors perform surgery

Can complex pediatric surgery interventions be standardized to facilitate telementoring?

two doctors perform surgery

The study’s authors write, “These discussions are particularly relevant to surgeons in small or rural practices who provide much-needed care to underserved populations and have decreased exposure to these index cases. Conversely, in some developing countries where prevalence of rare congenital surgical conditions is higher, there is a shortage of adequately trained pediatric surgeons. Each of these scenarios involves a mismatch in experience and exposure, which can result in poor patient outcomes and inadequate healthcare delivery.”

How does a surgeon-in-training get enough exposure to rare or complex cases to serve the patients who need them? How does a practicing surgeon perform enough cases each year to maintain proficiency at such index cases?

The authors of a study in the Journal of Pediatric Surgery, including Marc Levitt, M.D., chief of the Division of Colorectal and Pelvic Reconstruction at Children’s National Hospital, write that, “These discussions are particularly relevant to surgeons in small or rural practices who provide much-needed care to underserved populations and have decreased exposure to these index cases. Conversely, in some developing countries where prevalence of rare congenital surgical conditions is higher, there is a shortage of adequately trained pediatric surgeons. Each of these scenarios involves a mismatch in experience and exposure, which can result in poor patient outcomes and inadequate healthcare delivery.”

Telementoring is one strategy being explored by the American College of Surgeons’ Telementoring Task Force initiative. Pediatric anorectal malformations (ARM), pediatric colorectal surgical procedure, posterior sagittal anorectoplasty (PSARP) were the “index” areas for the pilot study. Once the expert established the areas of great need, they will test the feasibility of a curriculum and training program using telementoring in pediatric surgery. The ACS Task Force notes that these conditions are relatively rare and require a particular skill level to manage appropriately, making them good candidates for the study.

The Journal of Pediatric Surgery study presents a process for mapping out a standardized curriculum for these procedures. First, the authors sought expert consensus on three interoperative checklists that form a de facto curriculum for teaching, learning and performing ARM and PSARP procedures. Second, a multidisciplinary team of medical educators and pediatric surgery experts drafted the checklists. The authors then sought review and input from pediatric colorectal surgery experts at 10 institutions worldwide, who comprised the study’s colorectal pediatric surgery subject matter expert panel. To be considered “expert,” participants had to meet or exceed several strict inclusion criteria related to years in practice and experience with these case types.

Institutions of the colorectal pediatric surgery subject matter expert panel.

Institutions of the colorectal pediatric surgery subject matter expert panel.

The process led to a successful set of consensus documents. “To our knowledge, this is the first study to establish and standardize key intraoperative objectives using a modified-Delphi method in pediatric surgery,” the authors write. “Although this process can be quite time consuming, it provides an incredible opportunity to standardize intraoperative teaching and expectations of trainees. Future studies will expand these checklists into developing a competency assessment tool involving assessment for validity and reliability in a clinical setting to ultimately improve patient safety through standardization.”

Dr. Levitt says the overarching goal of this work is “to improve the surgical technique everywhere [to] thereby help as many kids as we can, even those we will never meet.”

US News badges

For fifth year in a row, Children’s National Hospital nationally ranked a top 10 children’s hospital

US News badges

Children’s National Hospital in Washington, D.C., was ranked in the top 10 nationally in the U.S. News & World Report 2021-22 Best Children’s Hospitals annual rankings. This marks the fifth straight year Children’s National has made the Honor Roll list, which ranks the top 10 children’s hospitals nationwide. In addition, its neonatology program, which provides newborn intensive care, ranked No.1 among all children’s hospitals for the fifth year in a row.

For the eleventh straight year, Children’s National also ranked in all 10 specialty services, with seven specialties ranked in the top 10.

“It is always spectacular to be named one of the nation’s best children’s hospitals, but this year more than ever,” says Kurt Newman, M.D., president and CEO of Children’s National. “Every member of our organization helped us achieve this level of excellence, and they did it while sacrificing so much in order to help our country respond to and recover from the COVID-19 pandemic.”

“When choosing a hospital for a sick child, many parents want specialized expertise, convenience and caring medical professionals,” said Ben Harder, chief of health analysis and managing editor at U.S. News. “The Best Children’s Hospitals rankings have always highlighted hospitals that excel in specialized care. As the pandemic continues to affect travel, finding high-quality care close to home has never been more important.”

The annual rankings are the most comprehensive source of quality-related information on U.S. pediatric hospitals. The rankings recognize the nation’s top 50 pediatric hospitals based on a scoring system developed by U.S. News. The top 10 scorers are awarded a distinction called the Honor Roll.

The bulk of the score for each specialty service is based on quality and outcomes data. The process includes a survey of relevant specialists across the country, who are asked to list hospitals they believe provide the best care for patients with the most complex conditions.

Below are links to the seven Children’s National specialty services that U.S. News ranked in the top 10 nationally:

The other three specialties ranked among the top 50 were cardiology and heart surgery, gastroenterology and gastro-intestinal surgery, and urology.

3D Illustration Concept of Human Urinary System

Predicting surgery risk through single diuretic renogram

3D Illustration Concept of Human Urinary System

In a new study published in the Journal of Pediatric Urology, Aaron Krill, M.D., urologist at Children’s National Hospital and leading author, shows that halftime from a single initial diuretic renogram in children with antenatally detected UPJO is predictive not only of worsening future drainage, but also of future surgical repair (pyeloplasty).

The findings of a new study show promising results that will help to further subdivide the indeterminate drainage range and will help practitioners identify those children at increased risk for worsening drainage and future surgery.

So far, we know that spontaneous resolution of antenatally detected kidney obstruction, also known as ureteropelvic junction obstruction (UPJO), is relatively common. However, it can take several years and require frequent surveillance ultrasounds and diuretic renograms before patients reach a clinical outcome.

The study, which published in the Journal of Pediatric Urology, and was led by Aaron Krill, M.D., urologist at Children’s National Hospital, shows that halftime (T1/2) from a single initial diuretic renogram in children with antenatally detected UPJ obstruction is predictive not only of worsening future drainage, but also of future surgical repair (pyeloplasty).

“Among infants with UPJO, 52 to 79% can be expected to undergo spontaneous improvement,” Dr. Krill said.

Initial nonoperative management has become the standard of care for cases with indeterminate drainage patterns with preserved differential renal function (DRF). Diuretic renography has traditionally been the gold standard for diagnosis and surveillance of this condition. Identification of patients with very good drainage who can safely be discharged and those with very poor drainage who require early surgical repair has never been difficult. However, patients with indeterminate drainage have posed a unique diagnostic and therapeutic problem. Previously published ranges for indeterminate drainage were either too wide or too narrow to be clinically useful.

In the study, recent data shows a five-year surgery-free survival probability for patients with t1/2 of 5-20, 21-40 and 41-60 minutes to be: 79.7%, 46.7% and 33.3%. This suggests that patients with t1/2 of more than 21 minutes are at moderate to high risk of requiring surgery within the first five years of life while those with t1/2 20 minutes or less are at relatively low risk.

“This would allow us to concentrate our efforts appropriately on those who are at high risk of progressing to surgery and minimize the burden of testing and that of radiation exposure for children who are at low risk and likely to improve spontaneously,” Dr. Krill added.

Researchers identified patients younger than 18 months at presentation with unilateral, isolated moderate to severe hydronephrosis who underwent diuresis renography from 2000-2016. This group was sub-divided into three T1/2 intervals: 5-20, 21-40 and 41-60 minutes. Endpoints were pyeloplasty and pyeloplasty free survival. Indications for surgery were loss of DRF, worsening T1/2, family preference and/or pain.

“Being told that your newborn has an obstructed kidney and may require surgery in the future is typically a very stressful event for families,” Dr. Krill said. “Now after only a single diuretic renogram, we can provide families with accurate probability estimates of their child’s lifetime risk of surgery and risk of surgery within their first five years. This should allow us to appropriately set expectations and customize our surveillance routine for each patient.”

For decades, Children’s National has been working to refine and standardize diuretic renography. Some accomplishments over the years include establishing the safety of the test in infants, verifying its diagnostic utility, identifying new drainage parameters, and coupling it with machine learning to improve accuracy. This most recent manuscript capitalizes on a large database spanning 20 years of the team’s clinical experience to further improve the ability to predict who will need surgical repair and better counsel our patients.

Other authors include Briony K. Varda, M.D., M.P.H., Nicholas A. Freidberg, Md Sohel Rana, M.B.B.S., M.P.H., Eglal Shalaby-Rana, M.D., Bruce M. Sprague and Hans G. Pohl, M.D.

Micrograph of human parasite Schistosoma mansonii

Diagnosing and monitoring of urogenital schistosomiasis

Micrograph of human parasite Schistosoma mansonii

Urogenital schistosomiasis (UGS) is caused by egg-laying S. haematobium worms dwelling within the veins draining the main pelvic organs, including the bladder, uterus, and cervix.

Although urogenital schistosomiasis remains a major global challenge, Michael Hsieh, M.D., Ph.D., director of Transitional Urology at Children’s National Hospital, and other experts including Eglal Shalaby Rana, M.D., from Children’s National, show in a new study published in Advances in Parasitology that newer refinements in associated technologies may lead to improvements in patient care.

In addition, application of investigational imaging methods, such as confocal laser endomicroscopy and two-photon microscopy in urogenital schistosomiasis, are likely to contribute to the understanding of this infection’s pathogenesis.

Read the full study in Advances in Parasitology.

coronavirus

An analysis of articles on pediatric COVID-19 cases

coronavirus

In a recent editorial, Dr. Briony Varda commented on a systematic review and meta-analysis of articles reporting on pediatric cases of COVID-19.

In a recent editorial, Children’s National Hospital Pediatric Urologist Briony Varda, M.D., M.P.H., and Emilie K. Johnson, M.D., M.P.H., from Ann & Robert H. Lurie Children’s Hospital of Chicago, comment on a systematic review and meta-analysis of articles reporting on pediatric cases of coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection.

Their take home messages were that although COVID-19 is typically milder in children than in adults, children (particularly infants) do appear to have cardiac damage from COVID-19 which may be a consideration for preoperative evaluation among surgeons. They also note the MIS-C is another emerging concern for children following an infection with COVID-19.

Read the full editorial in the Journal of Pediatric Urology.

conceptual image of bladder cancer

Sensitivity to physical versus chemical factors in CAP

conceptual image of bladder cancer

To date, reactive oxygen species and reactive nitrogen species have been regarded as the key factors causing the observable cellular death of cold atmospheric plasma (CAP)-treated cancer cells. The chemical basis of the conventional CAP treatment highlights apoptosis as the main CAP-triggered cell death mechanism.

However, in a recent study published in the Journal of Physics, Michael Hsieh, M.D., Ph.D., director of Transitional Urology at Children’s National Hospital, and other experts demonstrated a strong anti-melanoma effect based on physically-based CAP treatment. The study, which also tested bladder cancer, compared the anti-cancer effect of chemically-based versus physically-based CAP treatment on four typical cancer cell lines in vitro.

Illustration of Bifidobacterium

Probiotic use in pediatric medicine

Illustration of Bifidobacterium

Probiotics have received significant attention within both the scientific and lay communities for their potential health-promoting properties, including the treatment or prevention of various conditions in children.

In a recent article published by Pediatric Research, Michael Hsieh, M.D., Ph.D., director of Transitional Urology at Children’s National Hospital, and other experts review the published data on use of specific probiotic strains for three common pediatric conditions: the prevention of urinary tract infections and antibiotic-associated diarrhea and the treatment of atopic dermatitis.

Lee Beers

Lee Beers, M.D., F.A.A.P, begins term as AAP president

Lee Beers

“The past year has been a stark reminder about the importance of partnership and working together toward common goals,” says Dr. Beers. “I am humbled and honored to be taking on this role at such a pivotal moment for the future health and safety of not only children, but the community at large.”

Lee Savio Beers, M.D., F.A.A.P., medical director of Community Health and Advocacy at the Child Health Advocacy Institute (CHAI) at Children’s National Hospital, has begun her term as president of the American Academy of Pediatrics (AAP). The AAP is an organization of 67,000 pediatricians committed to the optimal physical, mental and social health and well-being for all children – from infancy to adulthood.

“The past year has been a stark reminder about the importance of partnership and working together toward common goals,” says Dr. Beers. “I am humbled and honored to be taking on this role at such a pivotal moment for the future health and safety of not only children, but the community at large.”

Dr. Beers has pledged to continue AAP’s advocacy and public policy efforts and to further enhance membership diversity and inclusion. Among her signature issues:

  • Partnering with patients, families, communities, mental health providers and pediatricians to co-design systems to bolster children’s resiliency and to alleviate growing pediatric mental health concerns.
  • Continuing to support pediatricians during the COVID-19 pandemic with a focus on education, pediatric practice support, vaccine delivery systems and physician wellness.
  • Implementation of the AAP’s Equity Agenda and Year 1 Equity Workplan.

Dr. Beers is looking forward to continuing her work bringing together the diverse voices of pediatricians, children and families as well as other organizations to support improving the health of all children.

“Dr. Beers has devoted her career to helping children,” says Kurt Newman, M.D., president and chief executive officer of Children’s National. “She has developed a national advocacy platform for children and will be of tremendous service to children within AAP national leadership.”

Read more about Dr. Beer’s career and appointment as president of the AAP.

Briony Varda

Q&A with urologist Briony Varda

Briony Varda

Briony Varda, M.D., M.P.H., is fellowship trained in pediatric genitourinary reconstructive surgery and her subspecialty interests include the care of patients with spina bifida and the neurogenic bladder, cloacal anomalies, hydronephrosis, vesicoureteral reflux and posterior urethral valves, among others.

Children’s National Hospital recognizes many urologic disorders and illnesses that are unique to children. As such, we pride ourselves in working with top urology experts, including Briony Varda, M.D., M.P.H., pediatric urologist, who recently joined the Urology Division at Children’s National.

Dr. Varda is fellowship trained in pediatric genitourinary reconstructive surgery and her subspecialty interests include the care of patients with spina bifida and the neurogenic bladder, cloacal anomalies, hydronephrosis, vesicoureteral reflux and posterior urethral valves, among others.

Here, Dr. Varda tells us more about her work and what it means for the future of pediatric urology patients at Children’s National.

Q: Why did you decide to work in this field?

I have always thoroughly enjoyed working with children. They keep you on your toes, tell it straight, make you laugh and demonstrate unique resilience. At the same time, surgery allows me to work with my hands, while being creative and helping others. Finally, I had great mentors within pediatric urology who strongly influenced me in a positive way.

In sum, the kids, the surgery and the people led me here.

Q: What is the importance of urology care?

We have three goals in pediatric urology: protect the kidneys and bladder, prevent infection and help our patients stay dry.

Although it’s usually clear when kids have urinary tract infections or trouble with urinary accidents, it’s not always visible when there is a problem with the kidney or bladder. Urologic care is therefore important because it prevents long-term damage that might otherwise go unnoticed until it is too late. This is particularly true for patients with abnormal functioning of the bladder related to a neurologic cause, such as spina bifida or a tethered spinal cord.

Q: How has the program expanded and what are some of the most valuable changes you hope to see in the next couple of years?

Our Spina Bifida Program currently includes physicians from physical medicine and rehabilitation (PMNR), orthopedics, neurosurgery and urology. Our newest additions include a full-time nurse practitioner who facilitates care coordination and has a clinical expertise in bowel management, two new urologists (myself and Christina Ho, M.D.), and Mi Ran Shin, M.D., who is our new PMNR physician.

We are also collaborating closely with the new Pediatric Colorectal & Pelvic Reconstruction Division for patients who need advanced bowel management. These additions will go a long way to helping improve the day-to-day living of our patients and help improve their long-term medical outcomes.

In the coming year, we are anticipating welcoming another full-time nurse to our program, offering more patient-facing resources including a webpage focused on urodynamics and an array of new patient education materials. We are also hoping to establish a regional transitional care network for our adolescent and young-adult patients.

Q: The Colorectal Program at Children’s National includes three urologists. How does this collaboration allow for the care of more complex cases at this hospital?

We are fortunate to be part of the Colorectal Program here at Children’s National Hospital. We provide subspecialty expertise for patients born with anorectal malformations, including cloacal anomalies and cloacal exstrophy. Although historically considered a general surgery problem, patients with anorectal malformations have a high rate of concomitant conditions affecting their genitourinary anatomy and function. By coordinating clinical care and surgery within a multidisciplinary team, we provide comprehensive care for even the most complex patients – nothing goes unnoticed and each subspecialist provides a unique perspective on management as it relates to their field.  Along with ourselves and the colorectal surgeons, we regularly collaborate with gynecology, gastroenterology, interventional radiology and anesthesia.

Q:  What is some of the research you’re working on now that you’re looking forward to the most?

We are currently designing a set of research projects aimed at investigating low-value healthcare utilization (for example, emergency room use and inappropriate testing) among patients with spina bifida. I plan to investigate institutional patterns and then expand out to the Washington, D.C., Maryland, Virginia area and the national setting. By identifying patterns in low-value healthcare utilization and their associated factors, we can ideally improve care delivery for this special healthcare needs population.

We are also working on institutional protocols to enact recently published guidelines by the Spina Bifida Association and the CDC so that we can eventually contribute our own data to national registries. This will pave the way for increasingly rigorous spina bifida research in the future.

Cover of the December issue of Seminars on Pediatric Surger

Reflections on Seminars in Pediatric Surgery December 2020

Cover of the December issue of Seminars on Pediatric Surger

Marc Levitt, M.D., served as guest editor of a special December Seminars in Pediatric Surgery dedicated to the care and treatment of anorectal malformations.

By Marc Levitt, M.D., chief of the Division of Colorectal and Pelvic Reconstruction at Children’s National Hospital

I was honored to serve as the Guest Editor on the topic of “Anorectal Malformations” in the prestigious Seminars in Pediatric Surgery Volume 29, Issue 6, December 2020.

We had 64 contributing authors from 12 countries; Australia, Austria, Germany, Ghana, Italy, Israel, the Netherlands, Nigeria, Spain, South Africa, the United Kingdom and the United States, and 12 U.S. colorectal collaborating programs; Children’s National, Boston Children’s, Children’s Mercy, Children’s Wisconsin, C.S. Mott Children’s, Cincinnati Children’s, Nationwide Children’s, Nicklaus Children’s, Omaha Children’s, Primary Children’s, Seattle Children’s, and UC Davis Children’s.

There were eight authors from the Children’s National team; myself, Colorectal Director Andrea Badillo, M.D., Colorectal Program Manager Julie Choueiki, MSN, RN, Surgical Center Director Susan Callicott, Katie Worst, CPNP-AC, Grace Ma, M.D., Chief of Urology Hans Pohl, M.D., and Chief of Gynecology Veronica Gomez-Lobo, M.D.

The series of articles included in this collection illustrate new techniques and ideas that over time have made a dramatic and positive impact on the care and quality of life of children who suffer from colorectal problems. With an integrated approach to the care of this complex group of patients, great things can be achieved. As we endeavor to advance this field, we need to always remember that, as Alberto Pena, M.D., often said, “it is not the unanswered questions, but rather the unquestioned answers that one must pursue.”

In my own article on advances in the field, a 2021 update, I reproduce a piece by my daughter, Jess Levitt, who wrote something applicable to the care of children with colorectal problems, with the message that helping to create order is vital to improve a somewhat chaotic medical process traditionally available for the care of complex care. Her essay is reproduced here:

“A” must come before “B,” which must come before “C,” everybody knows that. But what if the Millercamp’s of this world did not have to sit next to the Millerchip’s when it comes to seating arrangements? Can Pat Zawatsky be called before Jack Aaronson when the teacher is taking attendance? Do those 26 letters that make up all the dialogue, signs, thoughts, books, and titles in the English-speaking departments of the world need their specific spots in line? Everyone can sing you the well-known jingle from A to Z, but not many people can tell you why the alphabet is the way it is. For almost as long as humans have had the English language, they have had the alphabet. The good ole ABCs.

However, the alphabet represents the human need for order and stability. I believe that the same thinking that went into the construct of time and even government went into the alphabet. Justifiably, lack of order leads to chaos. Knife-throwing, gun-shooting chaos, in the case of lack of governmental order. Listen to me when I tell you that there is absolutely no reason that the alphabet is arranged the way that it is. Moreover, the alphabet is simply a product of human nature and how it leads people to establish order for things that do not require it. 

Now I know this sounds crazy but bear with me. Only if you really peel away the layers of the alphabet will you find the true weight it carries. People organized the letters of our speech into a specific order simply because there wasn’t already one. Questioning this order will enlighten you on the true meaning of it. Really dig deep into the meaning behind the social construct that is the alphabet. Short and sweet as it may be, the order of the ABCs is much less than meets the eye. There is no reason that “J” should fall before “K!” Understand this. Very important as order is, it is only a result of human nature.  What’s next? X-rays become independent of Xylophones in children’s books of ABCs? 

You know what the best part is? Zero chance you even noticed that each sentence in this essay is in alphabetical order.

Her literary contribution inspired me to do something similar. Take a look at the list of articles in this Seminars edition:

  1. Creating a collaborative program for the care of children with colorectal and pelvic problems. Alejandra Vilanova-Sánchez, Julie Choueiki, Caitlin A. Smith, Susan Callicot, Jason S. Frischer and Marc A. Levitt
  2. Optimal management of the newborn with an anorectal malformation and evaluation of their continence potential. Sebastian K. King, Wilfried Krois, Martin Lacher, Payam Saadai, Yaron Armon and Paola Midrio
  3. Lasting impact on children with an anorectal malformations with proper surgical preparation, respect for anatomic principles, and precise surgical management. Rebecca M. Rentea, Andrea T. Badillo, Stuart Hosie, Jonathan R. Sutcliffe and Belinda Dickie
  4. Long-term urologic and gynecologic follow-up and the importance of collaboration for patients with anorectal malformations. Clare Skerritt, Daniel G. Dajusta, Molly E. Fuchs, Hans Pohl, Veronica Gomez-Lobo and Geri Hewitt
  5. Assessing the previously repaired patient with an anorectal malformation who is not doing well. Victoria A. Lane, Juan Calisto, Ivo Deblaauw, Casey M. Calkins, Inbal Samuk and Jeffrey R. Avansino
  6. Bowel management for the treatment of fecal incontinence and constipation in patients with anorectal malformations. Onnalisa Nash, Sarah Zobell, Katherine Worst and Michael D. Rollins
  7. Organizing the care of a patient with a cloacal malformation: Key steps and decision making for pre-, intra-, and post-operative repair. Richard J. Wood, Carlos A. Reck-Burneo, Alejandra Vilanova-Sanchez and Marc A. Levitt
  8. Radiology of anorectal malformations: What does the surgeon need to know? Matthew Ralls, Benjamin P. Thompson, Brent Adler, Grace Ma, D. Gregory Bates, Steve Kraus and Marcus Jarboe
  9. Adjuncts to bowel management for fecal incontinence and constipation, the role of surgery; appendicostomy, cecostomy, neoappendicostomy, and colonic resection. Devin R. Halleran, Cornelius E.J. Sloots, Megan K. Fuller and Karen Diefenbach
  10. Treating pediatric colorectal patients in low and middle income settings: Creative adaptation to the resources available. Giulia Brisighelli, Victor Etwire, Taiwo Lawal, Marion Arnold and Chris Westgarth-Taylor
  11. Importance of education and the role of the patient and family in the care of anorectal malformations. Greg Ryan, Stephanie Vyrostek, Dalia Aminoff, Kristina Booth, Sarah Driesbach, Meghan Fisher, Julie Gerberick, Michel Haanen, Chelsea Mullins, Lori Parker and Nicole Schwarzer
  12. Ongoing care for the patient with an anorectal malfromation; transitioning to adulthood. Alessandra Gasior, Paola Midrio, Dalia Aminoff and Michael Stanton
  13. New and exciting advances in pediatric colorectal and pelvic reconstructive surgery – 2021 update. Marc A. Levitt

The first letter of each article forms an acrostic of the word “COLLABORATION” which is the secret sauce behind any success in the field of pediatric colorectal care.

schistosome

Parasite-derived molecule could accelerate recovery from UTI

schistosome

Eggs from S. haematobium may produce the molecule IPSE to reduce the immune response against them, which happens to dampen UTI-induced bladder inflammation.

IPSE, a urogenital parasite-derived immunomodulatory molecule, can suppress bladder pathogenesis and anti-microbial peptide gene expression in bacterial urinary tract infection (UTI) according to a new study led by Michael Hsieh, Ph.D., director of Transitional Urology at Children’s National Hospital.

Half of all girls and women, and about 5% of boys and men, will have at least one urinary tract infection (UTI) in their lifetimes.

“Although antibiotics are very helpful for these infections, there are concerns that overuse of antibiotics may contribute to antibiotic-resistant infections,” Dr. Hsieh said. “There are also concerns that antibiotic therapy for UTI does not uniformly resolve infection-induced or inflammation-associated symptoms quickly.”

Parasitic infections are often associated with bacterial co-infections for unclear reasons. This may be true for urogenital schistosomiasis (caused by Schistosoma haematobium infection) and bacterial urinary tract co-infection (UTI), the study noted. Dr. Hsieh and other leading experts previously reported that this co-infection is facilitated by S. haematobium eggs triggering interleukin-4 (IL-4) production and sought to dissect the underlying mechanisms.

“Despite S. haematobium’s ability to make hosts more susceptible to UTI, we have identified IPSE, a bladder parasite protein, as a potential anti-inflammatory agent to accelerate recovery from UTI,” Dr. Hsieh explained. “S. haematobium eggs may produce IPSE to reduce the immune response against them, which happens to dampen UTI-induced bladder inflammation. It may be possible to develop IPSE as novel therapeutic to accelerate recovery from UTI.”

The study’s data showed that IPSE may play a major role in S. haematobium-associated urinary tract co-infection, although in an unexpected way. The study’s findings also indicated that IPSE either works in concert with other IL-4 -inducing factors to increase susceptibility of S. haematobium-infected hosts to bacterial co-infection or does not contribute to enchaining vulnerability to this co-infection.

You can find the full study published in Parasites and Vectors. Learn more about the Children’s National Department of Urology.

Marc Levitt plays with a patient

Reoperation of anorectal malformation repair restores continence, improves quality of life

Marc Levitt plays with a patient

Dr. Levitt has performed over 10,000 surgeries to address the wide spectrum of problems involving the colon and rectum — more than any other full time practicing pediatric surgeon in the world.

Patients with a previously repaired anorectal malformation (ARM) can suffer from complications which lead to incontinence. Reoperation can improve the anatomic result, but its impact on functional outcomes has previously been unclear.

Marc Levitt, M.D., chief of Colorectal and Pelvic Reconstructive Surgery at Children’s National, and Richard Wood, M.D., chief of Colorectal and Pelvic Reconstruction at Nationwide Children’s Hospital, co-led the study when they worked together in Columbus. They performed a retrospective cohort study, from 2014 to 2019, of patients with a previously repaired ARM who underwent another posterior sagittal anorectoplasty (PSARP) procedure, essentially redoing their first procedure. When results from the initial assessment were compared to 12 months after the redo surgery, they found that patients with fecal incontinence after an ARM repair can, with a reoperation, have their anatomy corrected, restoring continence for many and also improving their quality of life.

The study, published in the Journal of Pediatric Surgery, found that at one-year post-redo operation, 50 percent of the patients were on laxatives only, and 75 percent of those patients were completely continent. Overall, 77 percent of the patients were clean (1 or fewer accident per week) after their redo surgery and complication rates were low. Strictures were the most common complication seen after reoperations, as no dilations were performed, but were easily managed with a minor procedure. Surprisingly, 20 percent of patients with expected poor continence potential became fully continent on a laxative-based regimen after redo surgery. Traditionally, many of these children would not even be offered a redo surgery, given their perceived poor potential for bowel control.

The Division of Colorectal & Pelvic Reconstructive Surgery at Children’s National is the first in the mid-Atlantic region to fully integrate surgery, urology, gynecology and gastroenterology into one cohesive program for children. Dr. Levitt is a world-renowned surgeon who has performed over 10,000 surgeries to address the wide spectrum of problems involving the colon and rectum — more than any other full time practicing pediatric surgeon in the world.

This study shows that redo surgeries are a safe and effective option for patients with fecal incontinence after an anorectal malformation repair. The authors hope that the findings will lead to the ability to help more patients who suffer from complications and/or incontinence after a prior repaired ARM and who can benefit from an improvement in their colorectal anatomy.  After a reoperation, patients can expect to have improved quality of life because the outcome gives them more freedom and less worry about soiling accidents.

To access the full article published in the Journal of Pediatric Surgery click here.

EUPSA joint congress flyer

Decision making in pediatric colorectal surgery webinars

EUPSA joint congress flyer

Due to the global COVID-19 pandemic, the 1st Joint Congress of European Pediatric Surgeons’ Association (EUPSA), International Pediatric Endosurgery Group (IPEG), and European Society of Paediatric Endoscopic Surgeons (ESPES) in Vienna, Austria, was canceled.  Despite this, EUPSA’s Education Office continued to foster collaboration and further educational opportunities among members in order to maintain and improve high standards of surgical care for pediatric surgical patients around the globe.

This included a webinar of case discussions on “Decision Making in Pediatric Colorectal Surgery,” led by Marc Levitt, M.D., Colorectal and Pelvic Reconstructive Surgeon at Children’s National Hospital. The international panel included Giulia Brisighelli (Johannesburg, ZA) Martin Lacher (Leipzig, Germany), Paula Midrio (Triviso, Italy), Carlos Reck (Vienna, Austria), Pim Sloots (Rotterdam, Netherlands), Gaia Tamaro (EUPSA Education Office), Alejandra Villanova (Madrid, Spain), and Tomas Wester (Stockholm, Sweden).

Dr. Levitt has since presented follow-up webinars on the following topics:

  • Abnormal perineum
  • Twisted pullthrough in Hirschprung disease
  • Duhamel pullthrough in Total Colonic Hirschsprung
  • Vaginal atresia in a newborn with ARM 2

You can view the full webinars below:

US News Badges

Children’s National ranked a top 10 children’s hospital and No. 1 in newborn care nationally by U.S. News

US News Badges

Children’s National Hospital in Washington, D.C., was ranked No. 7 nationally in the U.S. News & World Report 2020-21 Best Children’s Hospitals annual rankings. This marks the fourth straight year Children’s National has made the list, which ranks the top 10 children’s hospitals nationwide.

In addition, its neonatology program, which provides newborn intensive care, ranked No.1 among all children’s hospitals for the fourth year in a row.

For the tenth straight year, Children’s National also ranked in all 10 specialty services, with seven specialties ranked in the top 10.

“Our number one goal is to provide the best care possible to children. Being recognized by U.S. News as one of the best hospitals reflects the strength that comes from putting children and their families first, and we are truly honored,” says Kurt Newman, M.D., president and CEO of Children’s National Hospital.

“This year, the news is especially meaningful, because our teams — like those at hospitals across the country — faced enormous challenges and worked heroically through a global pandemic to deliver excellent care.”

“Even in the midst of a pandemic, children have healthcare needs ranging from routine vaccinations to life-saving surgery and chemotherapy,” said Ben Harder, managing editor and chief of Health Analysis at U.S. News. “The Best Children’s Hospitals rankings are designed to help parents find quality medical care for a sick child and inform families’ conversations with pediatricians.”

The annual rankings are the most comprehensive source of quality-related information on U.S. pediatric hospitals. The rankings recognize the nation’s top 50 pediatric hospitals based on a scoring system developed by U.S. News. The top 10 scorers are awarded a distinction called the Honor Roll.

The bulk of the score for each specialty service is based on quality and outcomes data. The process includes a survey of relevant specialists across the country, who are asked to list hospitals they believe provide the best care for patients with the most complex conditions.

Below are links to the seven Children’s National specialty services that U.S. News ranked in the top 10 nationally:

The other three specialties ranked among the top 50 were cardiology and heart surgery, gastroenterology and gastro-intestinal surgery, and urology.

Vittorio Gallo and Mark Batshaw

Children’s National Research Institute releases annual report

Vittorio Gallo and Marc Batshaw

Children’s National Research Institute directors Vittorio Gallo, Ph.D., and Mark Batshaw, M.D.

The Children’s National Research Institute recently released its 2019-2020 academic annual report, titled 150 Years Stronger Through Discovery and Care to mark the hospital’s 150th birthday. Not only does the annual report give an overview of the institute’s research and education efforts, but it also gives a peek in to how the institute has mobilized to address the coronavirus pandemic.

“Our inaugural research program in 1947 began with a budget of less than $10,000 for the study of polio — a pressing health problem for Washington’s children at the time and a pandemic that many of us remember from our own childhoods,” says Vittorio Gallo, Ph.D., chief research officer at Children’s National Hospital and scientific director at Children’s National Research Institute. “Today, our research portfolio has grown to more than $75 million, and our 314 research faculty and their staff are dedicated to finding answers to many of the health challenges in childhood.”

Highlights from the Children’s National Research Institute annual report

  • In 2018, Children’s National began construction of its new Research & Innovation Campus (CNRIC) on 12 acres of land transferred by the U.S. Army as part of the decommissioning of the former Walter Reed Army Medical Center campus. In 2020, construction on the CNRIC will be complete, and in 2012, the Children’s National Research Institute will begin to transition to the campus.
  • In late 2019, a team of scientists led by Eric Vilain, M.D., Ph.D., director of the Center for Genetic Medicine Research, traveled to the Democratic Republic of Congo to collect samples from 60 individuals that will form the basis of a new reference genome data set. The researchers hope their project will generate better reference genome data for diverse populations, starting with those of Central African descent.
  • A gift of $5.7 million received by the Center for Translational Research’s director, Lisa Guay-Woodford, M.D., will reinforce close collaboration between research and clinical care to improve the care and treatment of children with polycystic kidney disease and other inherited renal disorders.
  • The Center for Neuroscience Research’s integration into the infrastructure of Children’s National Hospital has created a unique set of opportunities for scientists and clinicians to work together on pressing problems in children’s health.
  • Children’s National and the National Institute of Allergy and Infectious Diseases are tackling pediatric research across three main areas of mutual interest: primary immune deficiencies, food allergies and post-Lyme disease syndrome. Their shared goal is to conduct clinical and translational research that improves what we know about those conditions and how we care for children who have them.
  • An immunotherapy trial has allowed a little boy to be a kid again. In the two years since he received cellular immunotherapy, Matthew has shown no signs of a returning tumor — the longest span of time he’s been tumor-free since age 3.
  • In the past 6 years, the 104 device projects that came through the National Capital Consortium for Pediatric Device Innovation accelerator program raised $148,680,256 in follow-on funding.
  • Even though he’s watched more than 500 aspiring physicians pass through the Children’s National pediatric residency program, program director Dewesh Agrawal, M.D., still gets teary at every graduation.

Understanding and treating the novel coronavirus (COVID-19)

In a short period of time, Children’s National Research Institute has mobilized its scientists to address COVID-19, focusing on understanding the virus and advancing solutions to ameliorate the impact today and for future generations. Children’s National Research Institute Director Mark Batshaw, M.D., highlighted some of these efforts in the annual report:

  • Eric Vilain, M.D., Ph.D., director of the Center for Genetic Medicine Research, is looking at whether or not the microbiome of bacteria in the human nasal tract acts as a defensive shield against COVID-19.
  • Catherine Bollard, M.D., MBChB, director of the Center for Cancer and Immunology Research, and her team are seeing if they can “train” T cells to attack the invading coronavirus.
  • Sarah Mulkey, M.D., Ph.D., an investigator in the Center for Neuroscience Research and the Fetal Medicine Institute, is studying the effects of, and possible interventions for, coronavirus on the developing brain.

You can view the entire Children’s National Research Institute academic annual report online.

kidney ultrasound

Using computers to enhance hydronephrosis diagnosis

kidney ultrasound

Researchers at Children’s National Hospital are using quantitative imaging and machine intelligence to enhance care for children with a common kidney disease, and their initial results are very promising. Their technique provides an accurate way to predict earlier which children with hydronephrosis will need surgical intervention, simplifying and enhancing their care.

We live in a time of great uncertainty yet great promise, particularly when it comes to harnessing technology to improve lives. Researchers at Children’s National Hospital are using quantitative imaging and machine intelligence to enhance care for children with a common kidney disease, and their initial results are very promising. Their technique provides an accurate way to predict earlier which children with hydronephrosis will need surgical intervention, simplifying and enhancing their care.

Hydronephrosis means “water in the kidney” and is a condition in which a kidney doesn’t empty normally. One of the most frequently detected abnormalities on prenatal ultrasound, hydronephrosis affects up to 4.5% of all pregnancies and is often discovered prenatally or just after birth.

Although hydronephrosis in children sometimes resolves by itself, identifying which kidneys are obstructed and more likely to need intervention isn’t particularly easy. But it is critical. “Children with severe hydronephrosis over long periods of time can start losing kidney function to the point of losing a kidney,” says Marius George Linguraru, DPhil, MA, MSc, principal investigator of the project; director of Precision Medical Imaging Group at the Sheikh Zayed Institute for Pediatric Surgical Innovation; and professor of radiology, pediatrics and biomedical engineering at George Washington University.

Children with hydronephrosis face three levels of examination and intervention: ultrasound, nuclear imaging testing called diuresis renogram and surgery for the critical cases. “What we want to do with this project is stratify kids as early as possible,” Dr. Linguraru says. “The earlier we can predict, the better we can plan the clinical care for these kids.”

Ultrasound is used to see whether there is a blockage and try to determine hydronephrosis severity. “Ultrasound is non-invasive, non-radiating, and does not expose the child to any risk prenatally or postnatally,” Dr. Linguraru says. Ultrasound evaluations require a trained radiologist, but there’s a lot of variability. Radiologists have a grading system based on the ultrasound appearance of the kidney to determine whether the hydronephrosis is mild, moderate or severe, but studies show this isn’t predictive of longer term outcomes.

Children whose ultrasounds show concern will be referred to diuresis renogram. Costly, complex, invasive and irradiating, it tests how well the kidney empties. Although appropriate for good clinical indications, doctors try to minimize its use. “Management of hydronephrosis is complex,” Dr. Linguraru says. “We want to use ultrasound as much as possible and much less diuresis renogram.”

For those patients whose kidney is obstructed and eventually need surgical intervention, the sooner that decision can be made the better. “The more you wait for a kidney that is severely obstructed, the more function may be lost. If intervention is required, it’s preferable to do it early,” Dr. Linguraru says. Of course for the child whose hydronephrosis will likely resolve itself, intervention is not the best option.

Marius George Linguraru

“With our technique we are measuring physiological and anatomical changes in the ultrasound image of the kidney,” says Marius George Linguraru, DPhil, MA, MSc. “The human eye may find it difficult to put all this together, but the machine can do it. We use quantitative imaging to do deep phenotyping of the kidney and machine learning to interpret the data.”

Dr. Linguraru and the multidisciplinary team at Children’s National Hospital, including radiology and urology clinicians, are putting the power of computers to work interpreting subtleties in the ultrasound data that humans just can’t see. In their pilot study they found that 60% of the nuclear imaging tests could have been safely avoided without missing any of the critical cases of hydronephrosis. “With our technique we are measuring physiological and anatomical changes in the ultrasound image of the kidney,” Dr. Linguraru says. “The human eye may find it difficult to put all this together, but the machine can do it. We use quantitative imaging to do deep phenotyping of the kidney and machine learning to interpret the data.”

Results of the initial study indicate that kids who have a mild condition can be safely discharged earlier and the model can predict all those kids with obstructions and accelerate their diagnosis by sending them earlier to get further investigation. Dr. Linguraru says. “There are only benefits: some kids will get earlier diagnosis, some earlier discharges.”

The team also has a way to improve the interpretation of diuresis renograms. “We analyze the dynamics of the kidney’s drainage curve in quantifiable way. Using machine learning to interpret those results, we showed we can potentially discharge some kids earlier and accelerate intervention for the most severe cases instead of waiting and repeating the invasive tests,” he says. The framework has 93% accuracy, including 91% sensitivity and 96% specificity, to predict surgical cases, a significant improvement over clinical metrics’ accuracy.

The next step is a study connecting all the protocols. “Right now we have a study on ultrasound, a study on nuclear imaging, but we need to connect them so a child with hydronephrosis immediately benefits,” says Dr. Linguraru. Future work will focus on streamlining and accelerating diagnosis and intervention for kids who need it, both in prospective studies and hopefully clinically as well.

Hydronephrosis is an area in which machine learning can be applied to pediatric health in meaningful ways because of the sheer volume of cases.

“Machine learning algorithms work best when they are trained well on a lot of data,” Dr. Linguraru says. “Often in pediatric conditions, data are sparse because conditions are rare. Hydronephrosis is one of those areas that can really benefit from this new technological development because there is a big volume of patients. We are collecting more data, and we’re becoming smarter with these kinds of algorithms.”

Learn more about the Precision Medical Imaging Laboratory and its work to enhance clinical information in medical images to improve children’s health.

Schistosoma

Parasitic eggs trigger upregulation in genes associated with inflammation

Schistosoma

Of the 200 million people around the globe infected with Schistosomiasis, about 100 million of them were sickened by the parasite Schistosoma haematobium.

Of the 200 million people around the globe infected with Schistosomiasis, about 100 million of them were sickened by the parasite Schistosoma haematobium. As the body reacts to millions of eggs laid by the blood flukes, people can develop fever, cough and abdominal pain, according to the Centers for Disease Control and Prevention. Schistosomiasis triggered by S. haematobium can also include hematuria, bladder calcification and bladder cancer.

Despite the prevalence of this disease, there are few experimental models specifically designed to study it, and some tried-and-true preclinical models don’t display the full array of symptoms seen in humans. It’s also unclear how S. haematobium eggs deposited in the host bladder modulate local tissue gene expression.

To better understand the interplay between the parasite and its human host, a team led by Children’s National Hospital injected 6,000 S. haematobium eggs into the bladder wall of seven-week-old experimental models.

After four days, they isolated RNA for analysis, comparing differences in gene expression in various treatment groups, including those that had received the egg injection and experimental models whose bladders were not exposed to surgical intervention.

Using the Database for Annotation, Visualization and Integrated Discovery (DAVID) – a tool that helps researchers understand the biological meaning of a long list of genes – the team identified commonalities with other pathways, including malaria, rheumatoid arthritis and the p53 signaling pathway, the team recently presented during the American Society of Tropical Medicine and Hygiene 2019 annual meeting. Some 325 genes were differentially expressed, including 34 genes in common with previous microarray data.

“Of particular importance, we found upregulation in genes associated with inflammation and fibrosis. We also now know that the body may send it strongest response on the first day it encounters a bolus of eggs,” says Michael Hsieh, M.D., Ph.D., director of transitional urology at Children’s National, and the research project’s senior author. “Next, we need to repeat these experiments and further narrow the list of candidate genes to key genes associated with immunomodulation and bladder cancer.”

In addition to Dr. Hsieh, presentation co-authors include Lead Author Kenji Ishida, Children’s National; Evaristus Mbanefo and Nirad Banskota, National Institutes of Health; James Cody, Vigene Biosciences; Loc Le, Texas Tech University; and Neil Young, University of Melbourne.

Financial support for research described in this post was provided by the National Institutes of Health under award No. R01-DK113504.

clatharin cage viewed by electron microscopy

IPSE infiltrates nuclei through clathrin-mediated endocytosis

clatharin cage viewed by electron microscopy

IPSE, one of the important proteins excreted by the parasite Schistosoma mansoni, infiltrates human cellular nuclei through clathrin-coated vesicles, like this one.

IPSE, one of the important proteins excreted by the parasite Schistosoma mansoni infiltrates human cellular nuclei through clathrin-mediated endocytosis (a process by which cells absorb metabolites, hormones and proteins), a research team led by Children’s National Hospital reported during the American Society of Tropical Medicine and Hygiene 2019 annual meeting.

Because the public health toll from the disease this parasite causes, Schistosomiasis, is second only to malaria in global impact, research teams have been studying its inner workings to help create the next generation of therapies.

In susceptible host cells – like urothelial cells, which line the urinary tract – IPSE modulates gene expression, increasing cell proliferation and angiogenesis (formation of new blood vessels). On a positive note, neurons appear better able to fend off its nucleus-infiltrating ways.

“We know that IPSE contributes to the severity of symptoms in Schistosomiasis, which leads some patients to develop bladder cancer, which develops from the urothelial lining of the bladder. Our team’s carefully designed experiments reveal IPSE’s function in the urothelium and point to the potential of IPSE playing a therapeutic role outside of the bladder,” says Michael Hsieh, M.D., Ph.D., director of transitional urology at Children’s National and the research project’s senior author.

In addition to Dr. Hsieh, research co-authors include Evaristus Mbanefo, Ph.D.; Kenji Ishida, Ph.D.; Austin Hester, M.D.; Catherine Forster, M.D.; Rebecca Zee, M.D., Ph.D.; and Christina Ho, M.D., all of Children’s National; Franco Falcone, Ph.D., University of Nottingham; and Theodore Jardetzky, Ph.D., and Luke Pennington, M.D., Ph.D., candidate, both of Stanford University.

Financial support for research described in this post was provided by the National Institutes of Health under award No. R01-DK113504.