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Diagnosing Testicular Torsion before Urological Consultation and Imaging: Validation of the TWIST Score
Author's Accepted Manuscript Diagnosing Testicular Torsion before Urologic Consultation and Imaging: A Validation of the TWIST Score Kunj R. Sheth , Melise Keays , Gwen M. Grimsby , Candace F. Granberg , Vani S. Menon , Daniel G. DaJusta , Lauren Ostrov , Martinez Hill , Emma Sanchez , David Kuppermann , Clanton B. Harrison , Micah A. Jacobs , Rong Huang , Berk Burgu , Halim Hennes , Bruce J. Schlomer , Linda A. Baker
PII: DOI: Reference:
S0022-5347(16)00224-X 10.1016/j.juro.2016.01.101 JURO 13294
To appear in: The Journal of Urology Accepted Date: 15 January 2016 Please cite this article as: Sheth KR, Keays M, Grimsby GM, Granberg CF, Menon VS, DaJusta DG, Ostrov L, Hill M, Sanchez E, Kuppermann D, Harrison CB, Jacobs MA, Huang R, Burgu B, Hennes H, Schlomer BJ, Baker LA, Diagnosing Testicular Torsion before Urologic Consultation and Imaging: A Validation of the TWIST Score, The Journal of Urology® (2016), doi: 10.1016/j.juro.2016.01.101. DISCLAIMER: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our subscribers we are providing this early version of the article. The paper will be copy edited and typeset, and proof will be reviewed before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to The Journal pertain.
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Diagnosing Testicular Torsion before Urologic Consultation and Imaging: A Validation of the TWIST Score
Affiliations:
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Kunj R. Sheth1, Melise Keays2, Gwen M. Grimsby3, Candace F. Granberg4, Vani S. Menon1,8, Daniel G. DaJusta6, Lauren Ostrov8, Martinez Hill8, Emma Sanchez8, David Kuppermann7, Clanton B. Harrison1,8, Micah A. Jacobs1,8, Rong Huang8, Berk Burgu5, Halim Hennes1,8, Bruce J. Schlomer1,8, Linda A. Baker1,8 1
University of Texas Southwestern Medical Center, Dallas, TX Children’s Hospital of East Ontario, Ottawa, Ontario 3 Phoenix Children’s Hospital, Phoenix, AZ 4 Mayo Clinic, Rochester, MN 5 Nationwide Children’s Hospital, Columbus, OH 6 Harvard Medical School, Boston, MA 7 Ankara Üniversitesi Tıp Fakültesi, Ankara, Turkey 8 Children’s Health, Dallas, TX
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Address Correspondence To: Linda A Baker, MD Interim Chief of Pediatric Urology Children’s Health, Center for Pediatric Urology 2350 Stemmons Freeway 4th Floor, F4.04 Dallas, TX 75207 P: 214 456 2480 F: 214 456 8803 Email: [email protected]
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Descriptive Runninghead (41 characters, max 50): Diagnosing Testicular Torsion with TWIST score
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Keywords (up to 5): Diagnosis, Spermatic cord torsion, Scrotum, Ultrasound Funding: This study was supported by an NIH grant, R21DK092654 (PI: Baker, LA). Financial Disclosures: None Conflict of Interest: None Word count: Abstract (Limit 250): 250 Manuscript (Limit 2500): 2311 1
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Abstract
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PURPOSE: TWIST (Testicular Workup for Ischemia and Suspected Torsion) score uses urologic history and physical exam to assess risk of testis torsion. The parameters include testis swelling (2 points), hard testis (2), absent cremasteric reflex (1), nausea/vomiting (1), and high-riding testis (1). While TWIST has been validated when scored by urologists, its diagnostic accuracy amongst non-urologic providers is unknown. We assessed the utility of the TWIST score when collected by non-urologic non-physician providers, mirroring the ER evaluation of acute scrotal pain.
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MATERIALS AND METHODS: Pediatric patients with unilateral acute scrotum were prospectively enrolled in a NIH clinical trial. After undergoing basic history and physical exam training, EMTs calculated TWIST score and determined Tanner stage per a pictorial diagram. Clinical torsion was confirmed by surgical exploration. All data were captured into RedCap, and receiver operating characteristic (ROC) curves evaluated the diagnostic utility of TWIST.
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RESULTS: Of 128 patients (mean age 11.3), 44 (mean age 13.0) had torsion. TWIST score cutoff values of 0 and 6 derived from ROC analysis identified 31 high, 57 intermediate, and 40 low risk patients (positive predictive value 93.5%; negative predictive value 100%). CONCLUSIONS: TWIST score assessed by non-urologists, such as EMTs, is accurate. Low risk patients do not require ultrasound to rule out torsion. High risk patients can proceed directly to surgery, avoiding the ultrasound in >50% of patients. In the future, EMTs and/or ER triage personnel could calculate TWIST score to guide radiologic workup and immediate surgical intervention at initial assessment long before urologic consultation.
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Introduction Testicular torsion is one of the few pediatric urologic emergencies, accounting for only 10-15% of acute scrotum presentations1, 2 with an annual incidence of 3.8 per 100,000 pediatric
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patients.3 Intervention within 4-8 hours is critical to prevent permanent testicular loss or atrophy from compromised testicular arterial flow.4, 5 Thereafter, the testicle is often not salvageable resulting in orchiectomy rates of 32-41%.3, 6 While delayed ER presentation cannot be
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controlled, prompt and accurate diagnosis upon arrival is essential to identify patients requiring
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surgical detorsion.
The classic presentation for testicular torsion in pubertal males is acute onset unilateral testicular pain with nausea and vomiting. An absent cremasteric reflex has been considered specific for testicular torsion,7 although there are reports of torsion with present cremasteric reflex.8 Testicular swelling, tenderness and high lie are nonspecific, often making diagnosis
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solely on physical exam difficult.9 Therefore, testicular ultrasound with doppler is heavily relied upon for confirmation.10, 11 Since awaiting any imaging constitutes a time delay, risk scoring systems based on signs and symptoms only, such as the TWIST (Testicular Workup for Ischemia
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and Suspected Torsion) score, have been proposed.12
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Barbosa et al. devised and validated the TWIST scoring system, which assigns a summed TWIST score (range 0-7 points) based on the absence (0 points) or presence of the following 5 variables: testicular swelling (2 points), hard testicle (2), absent cremasteric reflex (1), nausea/vomiting (1) and high riding testis (1). Their ROC analysis yielded all binary variables. Thus, for the categories of testicular swelling and hard testis, patients could only receive a score of 0 or 2 points (no option for 1 point). Per their initial validation, patients at high risk for 3
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torsion (TWIST ≥ 5) could proceed straight to OR without imaging as the PPV was 100%. Patients with intermediate risk (TWIST = 3-4) required ultrasound to evaluate for torsion, and patients at low risk for torsion (TWIST ≤ 2) did not require scrotal ultrasound as the NPV was
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100%.12 However, the TWIST score does not account well for physiologic differences in
children, control for inter-observer variability, or substitute for medico-legal need of ultrasound documentation. In Barbosa et al. data were collected by urologists, but in practice, this would
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first be obtained by an ER provider prior to urology consultation. In the present study we
evaluate the utility of the TWIST score when measured by trained non-physician, non-urologic
an emergency setting.
Materials and Methods
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personnel, specifically EMTs, who are often the first medical providers to encounter patients in
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Study Population (Inclusion and Exclusion Criteria)
The study population was drawn from an NIH-funded prospective study evaluating the use of Near Infrared Spectroscopy (NIRS) in the diagnosis of torsion.13 Between March 2013
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and March 2015, we prospectively evaluated males aged one month to 21 presenting to a tertiary
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care pediatric ER with acute scrotum, defined as painful scrotum or testis, abdominal pain, and/or waddling gait ("Cowboy shuffle") from painful scrotum. Patients with synchronous bilateral testicular torsion or a previously known testicular or scrotal pathology were excluded in the study protocol due to inability to use the contralateral testis as an internal control for NIRS measurements. Additionally, we excluded patients with chronic respiratory, hematological or vascular problems that could affect total body tissue oxygenation levels, and thus NIRS measurements. 4
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Study Design Per the NIH study protocol, the ER was instructed to page the on-call EMT research personnel
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upon arrival of any patients with acute scrotum. Potentially eligible study subjects were approached by the on-call EMT and screened for inclusion and exclusion criteria. Informed consent and required study data were collected while patients were receiving care, ultrasound
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and/or surgery, avoiding any delay in care. Scrotal ultrasound was used as the gold standard for diagnosis of testicular torsion and was intended to be performed for all patients included in the
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study, unless the physician's clinical suspicion was high enough to forego ultrasound and proceed to the OR for urgent detorsion. Patients with no evidence of torsion on ultrasound were given a urology follow-up appointment in 2 weeks and ER warning signs. For all enrolled study patients, the research EMTs evaluated the patient, assigning binary
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components of the TWIST score and Tanner stage using a descriptive and pictorial table (see Figure 1). The EMT received no training specific to the scrotal exam or TWIST scoring, but rather relied on basic history and physical exam training they learned during EMT certification.
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Data Analysis
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Patients without complete TWIST score components were excluded from this study.
All collected data were entered into a RedCap database (CTSA NIH Grant
UL1TR001105)14 and extracted as needed for analysis. T-tests, Fischer’s exact test and Wilcoxan rank sum tests were used for comparisons. ROC curves were constructed to analyze and compare the performance of the TWIST score as a diagnostic test for torsion.15 Optimal cutoff values for low, intermediate, and high risk groups were chosen to maximize performance of the test, taking into account clinically meaningful results to optimize NPV and PPV while limiting false 5
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negatives and false positives. All statistical analysis was performed with Stata 12 (College
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Station, TX).
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Results Among the 316 patients assessed for eligibility, 115 did not meet study criteria and 47
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declined to participate. One patient was taken straight to the OR for high suspicion of torsion without ultrasound and 2 patients without torsion did not receive an ultrasound. One of these patients refused ultrasound and the other had low clinical suspicion and ultrasound was deferred
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per the ED. Both patients had Urology follow-up with no evidence of torsion at that time.
128/154 enrolled patients had all TWIST data available (Figure 2). 44/128 (34.4%) patients were
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diagnosed with torsion and surgically confirmed. Amongst those not diagnosed with torsion in the ER, no patients presented with missed torsion, although only 45% returned for clinical follow-up. Demographic characteristics of all patients with and without torsion are demonstrated in Table 1. Patients with torsion were older (13.0 vs 10.4 yrs, p = 0.001), were more likely to be white or black (p = 0.003), had higher Tanner stage (p < 0.001), and had lower median hours of
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pain prior to arrival (p = 0.01).
The TWIST score components and total score (range 0-7) distribution is shown in Table
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2. The median TWIST score for torsion patients was 6 and the median TWIST score of nontorsion patients was 1 (p < 0.001). The ROC curve using all points in the TWIST score had an
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AUC = 0.95 (95% CI 0.91-0.98) (Figure 3a). Clinically meaningful TWIST score cutoff values of 0 and 6 were used to categorize patients into low risk (TWIST = 0), intermediate risk (TWIST = 1-5), and high risk (TWIST ≥ 6) with an optimized AUC of 0.90 (95% CI 0.85-0.94) (Figure 3b). There were no patients with a TWIST score of 0 that had torsion, giving a negative predictive value (NPV) of 100% and specificity of 47.6%. Of those with TWIST ≥ 6, 29/31 had torsion for a positive predictive value (PPV) of 93.5% and a sensitivity of 65.9%. The two 7
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torsion patients with a TWIST score of 1 for nausea/vomiting were manually detorsed at and outside facility and operative room findings remained consistent with this.
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For Tanner stage 3-5 patients, a high risk TWIST score had a PPV of 100% and sensitivity of 65.6% (Figure 4a). In contrast, for Tanner stage 1-2 patients, a high risk TWIST score had a PPV of 77.8% and sensitivity of 70.0% (Figure 4b). The two patients with high risk
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TWIST score without testicular torsion were a Tanner 1 and Tanner 2 patient with torsion of the
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appendix testis.
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Discussion In this study, we assessed the TWIST score obtained by trained non-physician, non-
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urologic providers. In our population, the TWIST score performed well as a diagnostic test for torsion, although not as well as previously reported and with different optimal cutoff values.12 Based on our results we have devised an algorithm to evaluate patients who present to the ER
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with an acute scrotum (Figure 5).
In our population, no torsions were missed on follow-up and all patients taken to the
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operating room had torsion or testicular ischemia in the absence of torsion, indicating recent detorsion (spontaneous, manual by ER, or with anesthesia). In current practice, ultrasound is increasingly used to guide the diagnosis of testicular torsion,10, 11 with reported 100% sensitivity, 97.9% specificity and 98.1% diagnostic accuracy. 2 Thus, ultrasonography served as the gold
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standard in our study population although constituting a 30-60 minute time delay in diagnosis. Thus, there is a growing effort to return to traditional history and physical exam findings to diagnose torsion, decreasing the reliance on imaging, minimizing cost, and facilitating rapid
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surgical intervention.16-19 The TWIST score is easy to calculate with a simple patient evaluation.
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In our study, 29/44 (65.9%) testicular torsions were detectable by a high risk TWIST score (≥ 6) and only 2/31 (6.5%) in the high risk group without testicular torsion would undergo a negative unnecessary surgical exploration. Per our ROC analysis the high risk score cutoff was 6 rather than 5, which was reported previously.12 In our population 4/12 (33.3%) patients with a TWIST score of 5 did not have testicular torsion, which would lead to an unacceptably high negative exploration rate. Alternatively, a high risk cutoff of 7 would yield a 100% PPV, but lower sensitivity to 34.1%, leading to an optimal cutoff of 6. In addition, our low risk group cutoff of 0 9
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was different than previously published. 40/128 (31.3%) comprised the low risk group with no cases of testicular torsion (100% NPV). If the goal of a low risk TWIST score is to avoid use of ultrasound, then a NPV of 100% is necessary as a missed torsion is unacceptable. A scrotal
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ultrasound could be avoided in all low (31.3%) and high (24.2%) risk patients, comprising over 50% of patients. In comparison, Barbosa et al. found ultrasound unnecessary in ~80% of
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patients.12
Torsion has a bimodal age distribution with the first peak in the neonatal period and the
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second peak around puberty.20 While post-pubertal children usually present with severe testicular pain, identifying typical torsion symptoms and performing sonography to appropriately diagnose torsion is more challenging in prepubescent children.6, 21 In our study, the two patients without torsion who were in the high risk group were Tanner stage 1 or 2 with a diagnosis of torsion of
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the appendix testis that led to a high TWIST score.
In Tanner stage 3-5 patients, the high risk TWIST score had a PPV of 100%, signifying that the TWIST score performs better for peri-pubertal or post-pubertal children. TWIST also
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performs well in Tanner 1-2 patients, but some of these children with torsion of appendix testis will be categorized as high risk for torsion. Therefore, ultrasound should be considered for these
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patients to help confirm diagnosis.
One key difference and asset in this validation of the TWIST score that may explain the
differences in group stratification is that all the involved components were collected by nonphysician, non-urologic personnel. At presentation, a urologist is typically not immediately available in the ER and the initial evaluation and decision to obtain an ultrasound or not is quite often done by non-urologists. Thus, we suggest the cutoff values seen in our study are more valid 10
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for use in the ER. Implementation and evaluation of the TWIST score by ER providers and triage nurses following our diagnostic algorithm will be the next step to potentially expedite urologic consultation and minimize time to the OR. Taking this one step further, validating EMT-
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generated TWIST scoring opens the door to early risk stratification in the field or during transit to the hospital, analogous to Glasgow Coma Scale use. Such rapid triage could allow for
expedited care on arrival for patients with TWIST ≥ 6, bypassing the ER with direct transport to
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the OR. Of course, this time-saving approach would require further investigation and evaluation
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prior to routine implementation. Limitations
The NIH study was powered for NIRS performance to diagnose testicular torsion. Thus, this secondary outcome sub-analysis evaluating TWIST score performance is limited by the small
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number of patients. Similarly, patients without torsion in the ER had poor follow-up, which could lead to misclassification of non-torsion patients. Furthermore, the TWIST score does not account for time since initial symptom onset. Generally, as torsion progresses, more signs and
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symptoms associated with the TWIST score will be present. Our tertiary care center is often a referral center for pediatric patients with testicular pain, and our torsion rate in this study of
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34.4% is much higher than reported in the literature (10-15%).1, 2 Many patients are transferred from outside hospitals, prolonging their duration of symptoms. Thus, our study cohort may represent a biased group of patients with prolonged torsion, enabling the TWIST score to be more diagnostic. Furthermore, the TWIST score does not incorporate severity of pain in risk stratifying patients. While this may be hard to quantify for patients, clinical suspicion tends to be higher when a patient presents with sudden onset severe pain. Lastly, the results are only 11
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applicable to the group of patients that were not excluded in our study due to prior testicular pathology or other medical co-morbidities. However, strengths of this study include the prospective internally controlled study design and the patient evaluation with TWIST scoring by
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non-physician, non-urologic staff. Conclusion
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The TWIST score was highly predictive in our population when evaluated by EMTs, especially in Tanner 3-5 patients where both the PPV and NPV were 100%. Therefore, our proposed
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algorithm can potentially guide emergency room physicians and staff to triage patients presenting with acute scrotum. Due to difficulty in definitive torsion diagnosis in Tanner 1 and 2 patients, we recommend obtaining an ultrasound even in high risk TWIST patients. Since low risk patients do not require ultrasound to rule out torsion and high risk patients Tanner 3-5 can
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proceed directly to surgery, ultrasound is safely avoided in >50% of patients.
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Boettcher M, Krebs T, Bergholz R et al: Clinical and sonographic features predict testicular torsion in children: a prospective study. BJU Int 2013, 112(8):1201-1206. Srinivasan A, Cinman N, Feber KM et al: History and physical examination findings predictive of testicular torsion: an attempt to promote clinical diagnosis by house staff. Journal of pediatric urology 2011, 7(4):470-474. Beni-Israel T, Goldman M, Bar Chaim S et al: Clinical predictors for testicular torsion as seen in the pediatric ED. The American journal of emergency medicine 2010, 28(7):786-789. Sharp VJ, Kieran K, Arlen AM: Testicular torsion: diagnosis, evaluation, and management. American family physician 2013, 88(12):835-840. Patriquin HB, Yazbeck S, Trinh B et al: Testicular torsion in infants and children: diagnosis with Doppler sonography. Radiology 1993, 188(3):781-785.
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Race
p-value 0.0011
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Mean age (SD)
Table 1: Patient characteristics Torsion (n=44) No torsion (n=84) 13.0 (4.0) 10.4 (4.4)
0.0032
11 (25.0%) 18 (40.9%) 14 (31.8%) 1 (2.3%) 0
16 (19.1%) 58 (69.1%) 9 (10.7%) 0 1 (1.2%)
Tanner stage (mean age)3 1 (6.3 yrs) 2 (10.8 yrs) 3 (13.7 yrs) 4 (15.3 yrs) 5 (15.0 yrs)
6 (14.3%) 4 (9.5%) 12 (28.6%) 17 (40.5%) 3 (7.1%)
28 (33.3%) 31 (36.9%) 11 (13.1%) 10 (11.9%) 4 (4.8%)
<0.0014
17.3 (0.6-129.3)
29.2 (0.9-346.1)
0.024
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Median hours of pain prior to arrival (range)
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White Hispanic Black Asian Other
Two-tailed t-test Fischer exact test used 3 Tanner stage missing in two patients with torsion 4 Wilcoxan rank sum test used due to non-normal distribution
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Table 1: Patient characteristics: This table describes patient demographics and characteristics in the torsion and non-torsion groups. The patients with torsion were found to be significantly older, more likely to be black or white, had a higher Tanner stage and shorter duration of pain.
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Table 2: TWIST score results Torsion (n=44) No torsion (n=84)
p-value
TWIST Score
TWIST Score Risk Category Low (0) Intermediate (1-5) High (6-7)
0 15 (34.1%) 29 (65.9%)
40 (47.6%) 42 (50.0%) 2 (2.4%)
<0.001
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40 (47.6%) 16 (19.1%) 9 (10.7%) 9 (10.7%) 4 (4.8%) 4 (4.8%) 2 (2.4%) 0
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0 3 (6.8%) 0 2 (4.6%) 2 (4.6%) 8 (18.2%) 14 (31.8%) 15 (34.1%)
<0.001
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0 1 2 3 4 5 6 7
Wilcoxan rank sum test used to compare groups due to non-normal distribution
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Table 2: TWIST score results: The individual components of the TWIST score are identified for all patients with and without torsion, and the break-up of patients in the low (0), intermediate (1-5), and high risk groups (6-7) are shown. There was no significant difference in the break-down of TWIST score components for patients with torsion when sub-stratified by Tanner stage.
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Figure 1:Tanner stage chart used by EMTs to identify patient Tanner stage at time of evaluation
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Figure 2: Study Consort Diagram
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Excluded (n=162) ♦ Not meeting inclusion criteria (n= 115) • Consent not properly obtained (n=16) • Comorbid conditions (n=23) • Obvious bug bites (n=11) • Bilateral scrotal pain (n=10) • Age less than 1 month (n=1) • No scrotal pain on assessment (n=21) • Did not follow study protocol (n=20) • Previous scrotal surgery (n=6) • Prior or chronic testis pain (n=7) ♦ Declined to participate (n= 47) ♦ Other reasons (n = 0)
Enrolled (n= 154)
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Assessed for eligibility (n = 316)
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TWIST data unavailable (n = 26)
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Analysed for primary endpoint (n= 128)
No testicular torsion on US – given clinical follow-up (n=82)
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Underwent scrotal ultrasound (n = 125)
Testicular torsion – confirmed on surgical exploration (n=44)
No scrotal ultrasound (n = 3)
Refused US (n = 1) Low suspicion for torsion, even at f/u
Low clinical suspicion, US deferred (n = 1); No torsion at f/u appt.
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Figure 3: ROC curve for TWIST score demonstrates an AUC of 0.95 (95% CI 0.91-0.98) (A). ROC curve for TWIST score risk categories demonstrates an AUC of 0.90 (95% CI 0.85-0.94) (B).
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Figure 4: ROC curve for TWIST score in Tanner 2-5 patients demonstrates an AUC of 0.95 (95% CI 0.91-0.99) (A). The ROC curve for TWIST score in Tanner 1 patients demonstrates an AUC of 0.96 (95% CI 0.91-1.00) (B). The cutoff risk category cutoff points (0 and 6) are circled in both ROC curves.
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Pediatric Patient with Acute Scrotum
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Figure 5: Proposed Diagnostic Algorithm for Testicular Torsion in the Acute Scrotum
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Calculate TWIST Score (0-7) and Tanner Stage (1-5)
Intermediate Risk
High Risk
(TWIST score = 0)
(TWIST score = 1-5)
(TWIST score ≥ 6)
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Low Risk
Obtain Scrotal US to evaluate
(No US necessary)
for testicular torsion
Tanner 3-5
Tanner 1-2
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No Testicular Torsion
Testicular torsion,
Consider Scrotal US prior to
proceed to OR (No US)
surgical exploration
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List of abbreviations: Testicular Workup for Ischemia and Suspected Torsion
ER
Emergency Room
EMT
Emergency Medical Technician
ROC
Receiver Operating Characteristics
PPV
Positive Predictive Value
NPV
Negative Predictive Value
NIRS
Near Infrared Spectroscopy
OR
Operating Room
MRI
Magnetic Resonance Imaging
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PII: DOI: Reference:
S0022-5347(16)00224-X 10.1016/j.juro.2016.01.101 JURO 13294
To appear in: The Journal of Urology Accepted Date: 15 January 2016 Please cite this article as: Sheth KR, Keays M, Grimsby GM, Granberg CF, Menon VS, DaJusta DG, Ostrov L, Hill M, Sanchez E, Kuppermann D, Harrison CB, Jacobs MA, Huang R, Burgu B, Hennes H, Schlomer BJ, Baker LA, Diagnosing Testicular Torsion before Urologic Consultation and Imaging: A Validation of the TWIST Score, The Journal of Urology® (2016), doi: 10.1016/j.juro.2016.01.101. DISCLAIMER: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our subscribers we are providing this early version of the article. The paper will be copy edited and typeset, and proof will be reviewed before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to The Journal pertain.
Embargo Policy All article content is under embargo until uncorrected proof of the article becomes available online. We will provide journalists and editors with full-text copies of the articles in question prior to the embargo date so that stories can be adequately researched and written. The standard embargo time is 12:01 AM ET on that date. Questions regarding embargo should be directed to [email protected].
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Diagnosing Testicular Torsion before Urologic Consultation and Imaging: A Validation of the TWIST Score
Affiliations:
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Kunj R. Sheth1, Melise Keays2, Gwen M. Grimsby3, Candace F. Granberg4, Vani S. Menon1,8, Daniel G. DaJusta6, Lauren Ostrov8, Martinez Hill8, Emma Sanchez8, David Kuppermann7, Clanton B. Harrison1,8, Micah A. Jacobs1,8, Rong Huang8, Berk Burgu5, Halim Hennes1,8, Bruce J. Schlomer1,8, Linda A. Baker1,8 1
University of Texas Southwestern Medical Center, Dallas, TX Children’s Hospital of East Ontario, Ottawa, Ontario 3 Phoenix Children’s Hospital, Phoenix, AZ 4 Mayo Clinic, Rochester, MN 5 Nationwide Children’s Hospital, Columbus, OH 6 Harvard Medical School, Boston, MA 7 Ankara Üniversitesi Tıp Fakültesi, Ankara, Turkey 8 Children’s Health, Dallas, TX
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Address Correspondence To: Linda A Baker, MD Interim Chief of Pediatric Urology Children’s Health, Center for Pediatric Urology 2350 Stemmons Freeway 4th Floor, F4.04 Dallas, TX 75207 P: 214 456 2480 F: 214 456 8803 Email: [email protected]
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Descriptive Runninghead (41 characters, max 50): Diagnosing Testicular Torsion with TWIST score
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Keywords (up to 5): Diagnosis, Spermatic cord torsion, Scrotum, Ultrasound Funding: This study was supported by an NIH grant, R21DK092654 (PI: Baker, LA). Financial Disclosures: None Conflict of Interest: None Word count: Abstract (Limit 250): 250 Manuscript (Limit 2500): 2311 1
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Abstract
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PURPOSE: TWIST (Testicular Workup for Ischemia and Suspected Torsion) score uses urologic history and physical exam to assess risk of testis torsion. The parameters include testis swelling (2 points), hard testis (2), absent cremasteric reflex (1), nausea/vomiting (1), and high-riding testis (1). While TWIST has been validated when scored by urologists, its diagnostic accuracy amongst non-urologic providers is unknown. We assessed the utility of the TWIST score when collected by non-urologic non-physician providers, mirroring the ER evaluation of acute scrotal pain.
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MATERIALS AND METHODS: Pediatric patients with unilateral acute scrotum were prospectively enrolled in a NIH clinical trial. After undergoing basic history and physical exam training, EMTs calculated TWIST score and determined Tanner stage per a pictorial diagram. Clinical torsion was confirmed by surgical exploration. All data were captured into RedCap, and receiver operating characteristic (ROC) curves evaluated the diagnostic utility of TWIST.
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RESULTS: Of 128 patients (mean age 11.3), 44 (mean age 13.0) had torsion. TWIST score cutoff values of 0 and 6 derived from ROC analysis identified 31 high, 57 intermediate, and 40 low risk patients (positive predictive value 93.5%; negative predictive value 100%). CONCLUSIONS: TWIST score assessed by non-urologists, such as EMTs, is accurate. Low risk patients do not require ultrasound to rule out torsion. High risk patients can proceed directly to surgery, avoiding the ultrasound in >50% of patients. In the future, EMTs and/or ER triage personnel could calculate TWIST score to guide radiologic workup and immediate surgical intervention at initial assessment long before urologic consultation.
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Introduction Testicular torsion is one of the few pediatric urologic emergencies, accounting for only 10-15% of acute scrotum presentations1, 2 with an annual incidence of 3.8 per 100,000 pediatric
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patients.3 Intervention within 4-8 hours is critical to prevent permanent testicular loss or atrophy from compromised testicular arterial flow.4, 5 Thereafter, the testicle is often not salvageable resulting in orchiectomy rates of 32-41%.3, 6 While delayed ER presentation cannot be
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controlled, prompt and accurate diagnosis upon arrival is essential to identify patients requiring
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surgical detorsion.
The classic presentation for testicular torsion in pubertal males is acute onset unilateral testicular pain with nausea and vomiting. An absent cremasteric reflex has been considered specific for testicular torsion,7 although there are reports of torsion with present cremasteric reflex.8 Testicular swelling, tenderness and high lie are nonspecific, often making diagnosis
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solely on physical exam difficult.9 Therefore, testicular ultrasound with doppler is heavily relied upon for confirmation.10, 11 Since awaiting any imaging constitutes a time delay, risk scoring systems based on signs and symptoms only, such as the TWIST (Testicular Workup for Ischemia
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and Suspected Torsion) score, have been proposed.12
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Barbosa et al. devised and validated the TWIST scoring system, which assigns a summed TWIST score (range 0-7 points) based on the absence (0 points) or presence of the following 5 variables: testicular swelling (2 points), hard testicle (2), absent cremasteric reflex (1), nausea/vomiting (1) and high riding testis (1). Their ROC analysis yielded all binary variables. Thus, for the categories of testicular swelling and hard testis, patients could only receive a score of 0 or 2 points (no option for 1 point). Per their initial validation, patients at high risk for 3
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torsion (TWIST ≥ 5) could proceed straight to OR without imaging as the PPV was 100%. Patients with intermediate risk (TWIST = 3-4) required ultrasound to evaluate for torsion, and patients at low risk for torsion (TWIST ≤ 2) did not require scrotal ultrasound as the NPV was
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100%.12 However, the TWIST score does not account well for physiologic differences in
children, control for inter-observer variability, or substitute for medico-legal need of ultrasound documentation. In Barbosa et al. data were collected by urologists, but in practice, this would
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first be obtained by an ER provider prior to urology consultation. In the present study we
evaluate the utility of the TWIST score when measured by trained non-physician, non-urologic
an emergency setting.
Materials and Methods
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personnel, specifically EMTs, who are often the first medical providers to encounter patients in
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Study Population (Inclusion and Exclusion Criteria)
The study population was drawn from an NIH-funded prospective study evaluating the use of Near Infrared Spectroscopy (NIRS) in the diagnosis of torsion.13 Between March 2013
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and March 2015, we prospectively evaluated males aged one month to 21 presenting to a tertiary
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care pediatric ER with acute scrotum, defined as painful scrotum or testis, abdominal pain, and/or waddling gait ("Cowboy shuffle") from painful scrotum. Patients with synchronous bilateral testicular torsion or a previously known testicular or scrotal pathology were excluded in the study protocol due to inability to use the contralateral testis as an internal control for NIRS measurements. Additionally, we excluded patients with chronic respiratory, hematological or vascular problems that could affect total body tissue oxygenation levels, and thus NIRS measurements. 4
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Study Design Per the NIH study protocol, the ER was instructed to page the on-call EMT research personnel
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upon arrival of any patients with acute scrotum. Potentially eligible study subjects were approached by the on-call EMT and screened for inclusion and exclusion criteria. Informed consent and required study data were collected while patients were receiving care, ultrasound
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and/or surgery, avoiding any delay in care. Scrotal ultrasound was used as the gold standard for diagnosis of testicular torsion and was intended to be performed for all patients included in the
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study, unless the physician's clinical suspicion was high enough to forego ultrasound and proceed to the OR for urgent detorsion. Patients with no evidence of torsion on ultrasound were given a urology follow-up appointment in 2 weeks and ER warning signs. For all enrolled study patients, the research EMTs evaluated the patient, assigning binary
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components of the TWIST score and Tanner stage using a descriptive and pictorial table (see Figure 1). The EMT received no training specific to the scrotal exam or TWIST scoring, but rather relied on basic history and physical exam training they learned during EMT certification.
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Data Analysis
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Patients without complete TWIST score components were excluded from this study.
All collected data were entered into a RedCap database (CTSA NIH Grant
UL1TR001105)14 and extracted as needed for analysis. T-tests, Fischer’s exact test and Wilcoxan rank sum tests were used for comparisons. ROC curves were constructed to analyze and compare the performance of the TWIST score as a diagnostic test for torsion.15 Optimal cutoff values for low, intermediate, and high risk groups were chosen to maximize performance of the test, taking into account clinically meaningful results to optimize NPV and PPV while limiting false 5
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negatives and false positives. All statistical analysis was performed with Stata 12 (College
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Station, TX).
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Results Among the 316 patients assessed for eligibility, 115 did not meet study criteria and 47
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declined to participate. One patient was taken straight to the OR for high suspicion of torsion without ultrasound and 2 patients without torsion did not receive an ultrasound. One of these patients refused ultrasound and the other had low clinical suspicion and ultrasound was deferred
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per the ED. Both patients had Urology follow-up with no evidence of torsion at that time.
128/154 enrolled patients had all TWIST data available (Figure 2). 44/128 (34.4%) patients were
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diagnosed with torsion and surgically confirmed. Amongst those not diagnosed with torsion in the ER, no patients presented with missed torsion, although only 45% returned for clinical follow-up. Demographic characteristics of all patients with and without torsion are demonstrated in Table 1. Patients with torsion were older (13.0 vs 10.4 yrs, p = 0.001), were more likely to be white or black (p = 0.003), had higher Tanner stage (p < 0.001), and had lower median hours of
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pain prior to arrival (p = 0.01).
The TWIST score components and total score (range 0-7) distribution is shown in Table
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2. The median TWIST score for torsion patients was 6 and the median TWIST score of nontorsion patients was 1 (p < 0.001). The ROC curve using all points in the TWIST score had an
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AUC = 0.95 (95% CI 0.91-0.98) (Figure 3a). Clinically meaningful TWIST score cutoff values of 0 and 6 were used to categorize patients into low risk (TWIST = 0), intermediate risk (TWIST = 1-5), and high risk (TWIST ≥ 6) with an optimized AUC of 0.90 (95% CI 0.85-0.94) (Figure 3b). There were no patients with a TWIST score of 0 that had torsion, giving a negative predictive value (NPV) of 100% and specificity of 47.6%. Of those with TWIST ≥ 6, 29/31 had torsion for a positive predictive value (PPV) of 93.5% and a sensitivity of 65.9%. The two 7
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torsion patients with a TWIST score of 1 for nausea/vomiting were manually detorsed at and outside facility and operative room findings remained consistent with this.
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For Tanner stage 3-5 patients, a high risk TWIST score had a PPV of 100% and sensitivity of 65.6% (Figure 4a). In contrast, for Tanner stage 1-2 patients, a high risk TWIST score had a PPV of 77.8% and sensitivity of 70.0% (Figure 4b). The two patients with high risk
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TWIST score without testicular torsion were a Tanner 1 and Tanner 2 patient with torsion of the
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appendix testis.
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Discussion In this study, we assessed the TWIST score obtained by trained non-physician, non-
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urologic providers. In our population, the TWIST score performed well as a diagnostic test for torsion, although not as well as previously reported and with different optimal cutoff values.12 Based on our results we have devised an algorithm to evaluate patients who present to the ER
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with an acute scrotum (Figure 5).
In our population, no torsions were missed on follow-up and all patients taken to the
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operating room had torsion or testicular ischemia in the absence of torsion, indicating recent detorsion (spontaneous, manual by ER, or with anesthesia). In current practice, ultrasound is increasingly used to guide the diagnosis of testicular torsion,10, 11 with reported 100% sensitivity, 97.9% specificity and 98.1% diagnostic accuracy. 2 Thus, ultrasonography served as the gold
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standard in our study population although constituting a 30-60 minute time delay in diagnosis. Thus, there is a growing effort to return to traditional history and physical exam findings to diagnose torsion, decreasing the reliance on imaging, minimizing cost, and facilitating rapid
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surgical intervention.16-19 The TWIST score is easy to calculate with a simple patient evaluation.
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In our study, 29/44 (65.9%) testicular torsions were detectable by a high risk TWIST score (≥ 6) and only 2/31 (6.5%) in the high risk group without testicular torsion would undergo a negative unnecessary surgical exploration. Per our ROC analysis the high risk score cutoff was 6 rather than 5, which was reported previously.12 In our population 4/12 (33.3%) patients with a TWIST score of 5 did not have testicular torsion, which would lead to an unacceptably high negative exploration rate. Alternatively, a high risk cutoff of 7 would yield a 100% PPV, but lower sensitivity to 34.1%, leading to an optimal cutoff of 6. In addition, our low risk group cutoff of 0 9
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was different than previously published. 40/128 (31.3%) comprised the low risk group with no cases of testicular torsion (100% NPV). If the goal of a low risk TWIST score is to avoid use of ultrasound, then a NPV of 100% is necessary as a missed torsion is unacceptable. A scrotal
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ultrasound could be avoided in all low (31.3%) and high (24.2%) risk patients, comprising over 50% of patients. In comparison, Barbosa et al. found ultrasound unnecessary in ~80% of
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patients.12
Torsion has a bimodal age distribution with the first peak in the neonatal period and the
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second peak around puberty.20 While post-pubertal children usually present with severe testicular pain, identifying typical torsion symptoms and performing sonography to appropriately diagnose torsion is more challenging in prepubescent children.6, 21 In our study, the two patients without torsion who were in the high risk group were Tanner stage 1 or 2 with a diagnosis of torsion of
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the appendix testis that led to a high TWIST score.
In Tanner stage 3-5 patients, the high risk TWIST score had a PPV of 100%, signifying that the TWIST score performs better for peri-pubertal or post-pubertal children. TWIST also
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performs well in Tanner 1-2 patients, but some of these children with torsion of appendix testis will be categorized as high risk for torsion. Therefore, ultrasound should be considered for these
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patients to help confirm diagnosis.
One key difference and asset in this validation of the TWIST score that may explain the
differences in group stratification is that all the involved components were collected by nonphysician, non-urologic personnel. At presentation, a urologist is typically not immediately available in the ER and the initial evaluation and decision to obtain an ultrasound or not is quite often done by non-urologists. Thus, we suggest the cutoff values seen in our study are more valid 10
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for use in the ER. Implementation and evaluation of the TWIST score by ER providers and triage nurses following our diagnostic algorithm will be the next step to potentially expedite urologic consultation and minimize time to the OR. Taking this one step further, validating EMT-
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generated TWIST scoring opens the door to early risk stratification in the field or during transit to the hospital, analogous to Glasgow Coma Scale use. Such rapid triage could allow for
expedited care on arrival for patients with TWIST ≥ 6, bypassing the ER with direct transport to
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the OR. Of course, this time-saving approach would require further investigation and evaluation
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prior to routine implementation. Limitations
The NIH study was powered for NIRS performance to diagnose testicular torsion. Thus, this secondary outcome sub-analysis evaluating TWIST score performance is limited by the small
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number of patients. Similarly, patients without torsion in the ER had poor follow-up, which could lead to misclassification of non-torsion patients. Furthermore, the TWIST score does not account for time since initial symptom onset. Generally, as torsion progresses, more signs and
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symptoms associated with the TWIST score will be present. Our tertiary care center is often a referral center for pediatric patients with testicular pain, and our torsion rate in this study of
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34.4% is much higher than reported in the literature (10-15%).1, 2 Many patients are transferred from outside hospitals, prolonging their duration of symptoms. Thus, our study cohort may represent a biased group of patients with prolonged torsion, enabling the TWIST score to be more diagnostic. Furthermore, the TWIST score does not incorporate severity of pain in risk stratifying patients. While this may be hard to quantify for patients, clinical suspicion tends to be higher when a patient presents with sudden onset severe pain. Lastly, the results are only 11
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applicable to the group of patients that were not excluded in our study due to prior testicular pathology or other medical co-morbidities. However, strengths of this study include the prospective internally controlled study design and the patient evaluation with TWIST scoring by
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non-physician, non-urologic staff. Conclusion
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The TWIST score was highly predictive in our population when evaluated by EMTs, especially in Tanner 3-5 patients where both the PPV and NPV were 100%. Therefore, our proposed
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algorithm can potentially guide emergency room physicians and staff to triage patients presenting with acute scrotum. Due to difficulty in definitive torsion diagnosis in Tanner 1 and 2 patients, we recommend obtaining an ultrasound even in high risk TWIST patients. Since low risk patients do not require ultrasound to rule out torsion and high risk patients Tanner 3-5 can
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proceed directly to surgery, ultrasound is safely avoided in >50% of patients.
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Boettcher M, Krebs T, Bergholz R et al: Clinical and sonographic features predict testicular torsion in children: a prospective study. BJU Int 2013, 112(8):1201-1206. Srinivasan A, Cinman N, Feber KM et al: History and physical examination findings predictive of testicular torsion: an attempt to promote clinical diagnosis by house staff. Journal of pediatric urology 2011, 7(4):470-474. Beni-Israel T, Goldman M, Bar Chaim S et al: Clinical predictors for testicular torsion as seen in the pediatric ED. The American journal of emergency medicine 2010, 28(7):786-789. Sharp VJ, Kieran K, Arlen AM: Testicular torsion: diagnosis, evaluation, and management. American family physician 2013, 88(12):835-840. Patriquin HB, Yazbeck S, Trinh B et al: Testicular torsion in infants and children: diagnosis with Doppler sonography. Radiology 1993, 188(3):781-785.
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Race
p-value 0.0011
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Mean age (SD)
Table 1: Patient characteristics Torsion (n=44) No torsion (n=84) 13.0 (4.0) 10.4 (4.4)
0.0032
11 (25.0%) 18 (40.9%) 14 (31.8%) 1 (2.3%) 0
16 (19.1%) 58 (69.1%) 9 (10.7%) 0 1 (1.2%)
Tanner stage (mean age)3 1 (6.3 yrs) 2 (10.8 yrs) 3 (13.7 yrs) 4 (15.3 yrs) 5 (15.0 yrs)
6 (14.3%) 4 (9.5%) 12 (28.6%) 17 (40.5%) 3 (7.1%)
28 (33.3%) 31 (36.9%) 11 (13.1%) 10 (11.9%) 4 (4.8%)
<0.0014
17.3 (0.6-129.3)
29.2 (0.9-346.1)
0.024
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Median hours of pain prior to arrival (range)
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White Hispanic Black Asian Other
Two-tailed t-test Fischer exact test used 3 Tanner stage missing in two patients with torsion 4 Wilcoxan rank sum test used due to non-normal distribution
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Table 1: Patient characteristics: This table describes patient demographics and characteristics in the torsion and non-torsion groups. The patients with torsion were found to be significantly older, more likely to be black or white, had a higher Tanner stage and shorter duration of pain.
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Table 2: TWIST score results Torsion (n=44) No torsion (n=84)
p-value
TWIST Score
TWIST Score Risk Category Low (0) Intermediate (1-5) High (6-7)
0 15 (34.1%) 29 (65.9%)
40 (47.6%) 42 (50.0%) 2 (2.4%)
<0.001
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40 (47.6%) 16 (19.1%) 9 (10.7%) 9 (10.7%) 4 (4.8%) 4 (4.8%) 2 (2.4%) 0
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0 3 (6.8%) 0 2 (4.6%) 2 (4.6%) 8 (18.2%) 14 (31.8%) 15 (34.1%)
<0.001
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0 1 2 3 4 5 6 7
Wilcoxan rank sum test used to compare groups due to non-normal distribution
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Table 2: TWIST score results: The individual components of the TWIST score are identified for all patients with and without torsion, and the break-up of patients in the low (0), intermediate (1-5), and high risk groups (6-7) are shown. There was no significant difference in the break-down of TWIST score components for patients with torsion when sub-stratified by Tanner stage.
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Figure 1:Tanner stage chart used by EMTs to identify patient Tanner stage at time of evaluation
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Figure 2: Study Consort Diagram
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Excluded (n=162) ♦ Not meeting inclusion criteria (n= 115) • Consent not properly obtained (n=16) • Comorbid conditions (n=23) • Obvious bug bites (n=11) • Bilateral scrotal pain (n=10) • Age less than 1 month (n=1) • No scrotal pain on assessment (n=21) • Did not follow study protocol (n=20) • Previous scrotal surgery (n=6) • Prior or chronic testis pain (n=7) ♦ Declined to participate (n= 47) ♦ Other reasons (n = 0)
Enrolled (n= 154)
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Assessed for eligibility (n = 316)
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TWIST data unavailable (n = 26)
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Analysed for primary endpoint (n= 128)
No testicular torsion on US – given clinical follow-up (n=82)
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Underwent scrotal ultrasound (n = 125)
Testicular torsion – confirmed on surgical exploration (n=44)
No scrotal ultrasound (n = 3)
Refused US (n = 1) Low suspicion for torsion, even at f/u
Low clinical suspicion, US deferred (n = 1); No torsion at f/u appt.
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Figure 3: ROC curve for TWIST score demonstrates an AUC of 0.95 (95% CI 0.91-0.98) (A). ROC curve for TWIST score risk categories demonstrates an AUC of 0.90 (95% CI 0.85-0.94) (B).
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Figure 4: ROC curve for TWIST score in Tanner 2-5 patients demonstrates an AUC of 0.95 (95% CI 0.91-0.99) (A). The ROC curve for TWIST score in Tanner 1 patients demonstrates an AUC of 0.96 (95% CI 0.91-1.00) (B). The cutoff risk category cutoff points (0 and 6) are circled in both ROC curves.
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Pediatric Patient with Acute Scrotum
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Figure 5: Proposed Diagnostic Algorithm for Testicular Torsion in the Acute Scrotum
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Calculate TWIST Score (0-7) and Tanner Stage (1-5)
Intermediate Risk
High Risk
(TWIST score = 0)
(TWIST score = 1-5)
(TWIST score ≥ 6)
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Low Risk
Obtain Scrotal US to evaluate
(No US necessary)
for testicular torsion
Tanner 3-5
Tanner 1-2
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No Testicular Torsion
Testicular torsion,
Consider Scrotal US prior to
proceed to OR (No US)
surgical exploration
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List of abbreviations: Testicular Workup for Ischemia and Suspected Torsion
ER
Emergency Room
EMT
Emergency Medical Technician
ROC
Receiver Operating Characteristics
PPV
Positive Predictive Value
NPV
Negative Predictive Value
NIRS
Near Infrared Spectroscopy
OR
Operating Room
MRI
Magnetic Resonance Imaging
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TWIST