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Key Highlights From Our 2021 Publications

Nov 22, 2021

The Division of Urology has published 96 pubmed indexed manuscripts.  This work is the combined efforts of all of the faculty in every section of the Division of Urology: Andrology, Men’s Health, Oncology, Pediatrics, and Reconstructive Urology.  I am most proud as chief of urology, not the number of publications, rather the scope and breadth of the work being done within the division.  Highlighted below are some of the key publications this year.

Andrology:

A study led by Associate Professor Ki Aston, PhD and his postdoctoral fellow Albert Salas-Huetos, was recently published in the Journal Human Genetics. This NIH-funded study, entitled “Disruption of human meiotic telomere complex genes TERB1, TERB2 and MAJIN in men with non-obstructive azoospermia,” began with the help of a Utah family in which several brothers had been diagnosed with azoospermia. Analysis of the genomes of the infertile brothers along with unaffected family members revealed the mutation of both copies of TERB2, a gene critical for meiosis, and thus sperm production. Through Dr. Aston’s international collaborations, mutations in related genes were discovered in other azoospermic men, suggesting that mutations in genes in the meiotic telomere complex are a recurrent cause of severe spermatogenic impairment. This, and other ongoing studies in Dr. Aston’s lab are critical for understanding the causes of infertility and ultimately designing personalized fertility treatment strategies in the future.

Men’s Health:

“Semen parameter thresholds and time-to-conception in subfertile couples: how high is high enough?” published in Human Reproduction.

This paper, published in Human Reproduction and was the first paper to demonstrate that the classically held notion that increasing total motile sperm count  (TMC) (millions of swimming sperm) over 20 million does not significantly improve chances of conception over time, was incorrect.  We found that men with a TMC>50M had a 45% greater chance of conceiving withing 5 years compared to those with TMC<50M.  Further, we found that those with TMC>50M conceived, on average in 19 months vs. 36 months for those with TMC<50M.  We also found that there was no upper limit to how chances of conception improved with increasing TMC.  This represents a paradigm shift in how we view the importance of evaluating the male partner of infertile couples. 

Oncology:

“Decision fatigue in low-value prostate cancer screening published in Cancer.

Low-value prostate cancer screening is testing in men who are unlikely to benefit such as in the elderly, infirm, really young, or those with recent normal PSA testing. Despite agreement that PSA testing in these men doesn’t help them, it remains a common practice. Why providers use PSA testing among men unlikely to benefit from it is poorly understood and likely complex. In this study, we explored whether a behavioral economic principle – decision fatigue – may explain some low-value PSA testing practices. Decision fatigue suggests that repetitive decision making leads to less favorable choices as cognitive resources deplete. We showed that decision fatigue likely explains some of the low-value PSA testing practices among primary care providers with lower value testing occurring later in the day and at the end of the work week. In addition to better understanding the contributors to low-value PSA testing, we hope that this work will help to design interventions to reduce low-value PSA testing. Clinical decision support has demonstrated efficacy for addressing behaviors when decision fatigue is at play. In future work, we plan to leverage clinical decision support to improve the value of prostate cancer screening.

Pediatric Urology:

There are “landmark” papers that urologists just know – either because they have read it themselves or heard from other learners or teachers about these seminal works in urology.  Examples include Walsh’s seminal paper describing the anatomic radical retropubic prostatectomy (J Urol Dec 1987) or Lapides’s introduction into the concept of clean intermittent catheterization for neurogenic bladder patients (J Urol Mar 1972). But what are the major papers that have shaped the (relatively) young field of pediatric urology? In an attempt to highlight the most significant papers in pediatric urology, Dr. Anthony Schaeffer and his fellow Dr. Rano Matta performed an analysis of the 100 top cited papers in pediatric urology. This list of the 100 most cited articles (published between 1900-2020)  provides both the reader with a reference for key manuscripts in pediatric urology (hypospadias, DSD, guidelines statements) and a student of pediatric urology with a bibliography of the most important contributions (and contributors) in the burgeoning field. While others have studied the top papers in hypospadias and other areas, this study nicely pulls together and summarizes the highest cited papers in pediatric urology. 

Trauma and Reconstructive Urology:

The University of Utah has investigated the link between nephrectomy and death, in the acute trauma setting. These studies first identified the association in a prospective clinical study conducted through University of Utah.  Investigators then approached the problem from a health services perspective and studied the link between nephrectomy and death in 2 large databases maintained by the American College of Surgeons, called the National Trauma Databank and the Trauma Quality Improvement Program. This work has resulted in three manuscripts in Urology and the Journal of Urology.

The strong association between nephrectomy and death was first identified in the Multi-institutional Genitourinary Trauma Study (MiGUTS). This study was run through University of Utah, Jeremy Myers, MD serving as PI, and was a collaboration with the American Association for the Surgery of Trauma. Dr. Mitch Heiner (current PYG4) and secondary author Dr. Soren Keihani (current PGY2) found in the greater than 1,100 high grade renal trauma patients, that even after adjusting for overall injury severity and shock, patients undergoing nephrectomy had an associated greater than a 2-fold increased risk of death. This study is one of the largest prospective studies that has ever been done in renal trauma, however, even so there were only 96 (9%) that died during the study. Due to these limitations, the findings were really hypothesis generating rather than firm evidence. The study was published in Urology and entitled “Nephrectomy after high-grade renal trauma is associated with increased mortality: Results from the Multi-institutional Genitourinary Trauma Study (MiGUTS).”

After finding this association investigators developed the hypothesis that nephrectomy decreased renal reserve in patients that were experiencing multi-systems trauma and these patients had a higher rate of AKI, which is highly associated with increased mortality after trauma. In order to investigate this further, the National Trauma Databank was used, which is a national database, including most level 1 trauma centers and maintained by the American Association for the Surgery of Trauma. In this study, Dr. Ross Anderson (a reconstructive urology fellow 2020) showed again an 80% associated increased risk of death after nephrectomy, even after adjusting for many factors that could increase mortality, such as shock on arrival, concomitant injuries, and overall injury severity. An important limitation of this study, which was entitled “Nephrectomy is associated with increased mortality after renal trauma: an analysis of the National Trauma Databank from 2007-2016” and published in the Journal of Urology, is that degree of blood transfusion was not available and death may have been driven by ongoing hemorrhage rather than nephrectomy.

In order to address this critique, Dr. Benjamin McCormick (reconstructive urology fellow 2021), used the Trauma Quality Improvement Program database, which had details about the volume of blood required in the first 24 hours of admission after trauma. In a paper, also published in Journal of Urology entitled Nephrectomy is not associated with increased risk of mortality or acute kidney injury after high-grade renal trauma: a propensity score analysis of the Trauma Quality Improvement Program (TQIP)” that it did indeed appear that the association between death and nephrectomy was primarily driven by degree of hemorrhage.  The process of investigating this link was an amazing exercise in developing strong evidence to inform guidelines and the trauma community and also the importance of being willing to disprove previously supported hypotheses.