A nomogram for predicting risk factors of testicular salvage after testicular torsion in children

This study aimed to establish a nomogram for predicting the probability of testicular salvage after testicular torsion in children.


INTRODUCTION
Testicular torsion is a common emergency in pediatric urology.The incidence of testicular torsion is approximately 0.004% in patients under 18 years of age, accounting for 52.5% of scrotal emergencies in children. 1,2Testicular torsion is the rotation of the testis and epididymis around the spermatic vessels.This causes testicular blood flow to either decrease or stop entirely.If the rotated state is not corrected in time, it could easily cause testicular ischemic damage and even necrosis. 3Some studies have pointed out that the success rate of testicular rescue within 6 h after testicular torsion is 90%-100% and drops to 0%-10% after 12-24 h. 4 In patients with testicular torsion, surgical exploration must be performed as soon as possible to restore the normal anatomical state of the testis and spermatic cord.Moreover, orchiectomy or orchiopexy should be considered based on testicular vitality.Of note, orchiopexy did not indicate successful testicular salvage.Testicular atrophy occurs in 16%-48% of patients who undergo orchiopexy after testicular torsion. 5,6In this study, the process of diagnosis and treatment of testicular torsion was regarded as a whole, and the relatively objective indices in patients with testicular torsion from onset to long-term follow-up were extracted and included in the study; the effects of various factors on testicular salvage were analyzed.We also established a prediction model for testicular salvage, which could provide a reference for clinicians and parents to understand the probability of testicular salvage in children with testicular torsion.

Patients' characteristics
This study was approved by the Institutional Review Board of Shenzhen Children's Hospital (No. 2022014).Using the medical record system of Shenzhen Children's Hospital, the medical records of children with testicular torsion treated in our hospital from September 2005 to August 2022 were extracted and reviewed.The dataset of this study consisted of two parts: training and verification cohorts.Children from September 2005 to January 2021 were included in the training cohort; a prediction model for testicular rescue was established based on the data of this cohort.We used children diagnosed with testicular torsion from February 2021 to August 2022 as the verification cohort for the predictive model to test the accuracy of the nomogram.
The inclusion criteria were the following: First, the patient's age being <18 years.Second, the children have been examined by a urologist at our hospital before surgery and underwent ultrasound examinations by ultrasound specialists at our hospital.Third, testicular torsion has been surgically confirmed.Fourth, the patients have been followed up for a postoperative period of at least 6 months.The exclusion criteria were the following: presence of a neonatal testicular torsion and presence of incomplete medical records or follow-up data.
In this study, the patients' clinical data were collected, including age; side of testicular torsion; clinical symptoms and signs; duration of symptoms (the time between the occurrence of symptoms and the beginning of surgery); ultrasound results; operation-related data; hematological parameters; and postoperative follow-up data.
Ultrasonographic examination was performed using Vivid 7, Voluson E8, and Logiq E9 color ultrasound instruments (GE Healthcare, Chicago, USA).With patients in the supine position, bilateral retroperitoneal, inguinal, scrotal, and testicular ultrasonography was performed.The position, shape, size, boundary, echo, color Doppler blood flow signal, and periphery of the testis were detected.Testicular volume was estimated using the ellipsoid formula (

Surgical procedures
After admission, all patients with scrotal emergency underwent physical examination, ultrasound, and blood routine examination.When testicular torsion was suspected, rapid treatment channels were provided immediately to ensure surgical exploration within 1 h.The children were placed in the supine position.After adequate anesthesia, according to the position of the testes, a groin incision or transverse scrotal incision was made to explore the spermatic vessels.If torsion of the spermatic vessels was found, the testis was raised out of the thecal capsule and restored.Blood circulation in the affected testis was observed after heating with warm water for 20 min.According to the Arda grade, to decide whether to retain the testis, we cut open the white membrane of the testis and observed bleeding in the section.The grades were Arda grade I, immediate blood oozing; Arda grade II, fresh blood exudation within 10 min; and Arda grade III, no fresh blood exudation beyond 10 min.Testicular preservation and orchiopexy were performed in those with Arda grades I and II, whereas orchiectomy was considered for grade III. 7

Grouping design
][10] The training cohort was divided into two groups: the successful and failed testicular salvage groups.The patients who received orchiectomy and those who experienced testicular atrophy following orchiopexy were categorized into the failed testicular salvage group, whereas those who did not develop testicular atrophy during follow-up were categorized into the testicular rescue success group. 2

Statistical analysis
This study primarily used SPSS 22.0 (IBM, Armonk, NY, USA), R 3.6.0(R Foundation for Statistical Computing, Vienna, Austria), and MedCalc 20.0.8 (Ostend, Belgium) for data analysis.First, a univariate analysis was performed to determine the relationship between all variables and testicular rescue after testicular torsion.To identify independent risk factors for testicular rescue, multivariate logistic regression analysis was performed.All significant predictors were analyzed using reduced-model multivariate analysis; the results were used to establish the prediction model formula.Finally, based on the prediction model formula, the nomogram was constructed using the rms package of R software.Finally, the bootstrap method was used to verify the nomogram by repeatedly sampling the verification group data for 1000 times.The receiver operating characteristic (ROC) curve of the participants was established.The area under the curve (AUC) was evaluated; the sensitivity and specificity were calculated.Categorical variables are presented as number of cases and percentages.Non-normally distributed continuous variables are presented as median with interquartile range.

RESULTS
Between September 2005 and January 2021, 187 children presented to our hospital with testicular torsion.Twenty cases of neonatal onset, seven of loss to follow-up after surgery, four missing the results of preoperative ultrasound examination in our hospital, and one patient whose parents refused surgical treatment in our hospital were excluded from the study.Ultimately, 155 patients with testicular torsion were included in the training cohort.The median age of the training cohort was 8.98 years (2.75-12.53years): 11.31 years (9.35-12.77years) in the successful testicular rescue group and 6.91 years (1.59-12.48years) in the testicular salvage failure group.A total of 113 patients underwent orchiectomy and 42 patients underwent orchiopexy, of which five developed testicular atrophy and were diagnosed with testicular salvage failure (Table 1).
From February 2021 to August 2022, 48 patients with testicular torsion were enrolled in the validation cohort (Table 3).The clinical records of the 48 patients in the verification cohort were fitted into the predictive model for verification.The results showed that the area under the ROC curve was 0.965 (95% CI, 0.867-0.997).When the cut-off value was 0.431, the sensitivity and specificity of the prediction model were 90.5% and 88.9%, respectively (Figure 1c).torsion. 11However, this study only focused on whether orchiectomy was performed during surgery, wherein a long-term follow-up of testicular atrophy in patients with orchiopexy was not performed.We suggest that considering testicular preservation during surgery does not mean successful testicular salvage of torsion; the process of ischemia-reperfusion injury should be regarded as a whole.When there is no testicular atrophy after orchiopexy, testicular salvage could be regarded as successful.The AUC of our predictive model was 0.965, indicating good predictability.This prediction model could not only provide a reference for surgeons to judge testicular activity during surgery but also answer parents' questions about long-term prognosis.Testicular torsion could occur in all age groups; its onset is bimodal.The first peak occurs during the newborn period, while the second peak takes place in teenagers between the  ages of 12 and 14 years. 12,13In this study, considering that some of the patients with neonatal testicular torsion had intrauterine torsion, there was inevitably a deviation in the statistics of such children's clinical data; thereby, neonatal testicular torsion was contained in the exclusion criteria.Wang et al. showed that the average age of patients undergoing orchiopexy was 11.00 AE 3.44 years, which was significantly higher than that in patients undergoing orchiectomy (6.76 AE 5.56 years). 14In this study, the age of onset in the successful testicular rescue and failed testicular salvage groups was 11.31 and 6.91 years, respectively.Although the difference between the two groups was statistically significant, multivariate logistic regression analysis revealed that age was not an independent risk factor for testicular rescue.
The duration of symptoms refers to the time from the onset of symptoms to surgical correction of torsion.This index could reflect the duration of testicular ischemia to a certain extent and is of great significance for the prediction of testicular rescue.Howe et al. conducted a retrospective analysis of the clinical data of 81 patients with testicular torsion and found that the average duration of symptoms in patients who underwent successful testicular salvage was 6.2 h (1-21 h) and 13.4 h (3-24 h) in those who underwent unsuccessful testicular salvage. 2 Ultrasonography could reveal the characteristics of the testicular parenchyma and blood perfusion, evaluating the vitality of the testicular parenchyma. 15The sensitivity of Doppler ultrasound in testicular torsion was 69%-91%, and the specificity was 87%-100%. 16If the ultrasonic texture of the twisted testis is normal, the possibility of testicular salvage could be higher.If some or all testes are hypoechoic, this suggests that there is an infarct in the testes.When secondary bleeding occurs, there may be a partial echo enhancement area around the infarcted area. 17Boettcher et al. revealed that the combination of clinical features and ultrasound results may improve the specificity of testicular torsion diagnoses, such as the rapid appearance of clinical symptoms and decrease or loss of central blood perfusion on color Doppler ultrasound, which often require early surgical exploration. 15n this study, multivariate logistic regression analysis showed that intratesticular blood flow on ultrasound was an independent risk factor for predicting testicular salvage (OR, 0.003; 95% CI, 0.001-0.070;p < 0.001).Ultrasound is highly dependent on operator experience and also necessary for guarding against the occurrence of false-negative results. 16,18n patients with suspected testicular torsion, testicular conditions could be determined using ultrasound.However, surgical exploration is still needed as soon as possible.
The blood supply to the testes mainly comes from the spermatic vessels.Therefore, their degree of torsion could reflect testicular ischemia in patients with testicular torsion to a certain extent.It has been indicated that when the torsion of spermatic cord vessels exceeded 450°, the blood supply to the testes would be completely interrupted. 19Howe et al. pointed out that when intraoperative exploration found that the torsion of the spermatic cord was >360°, the risk of testicular irreparability was higher. 2 Clarifying that the degree of spermatic cord torsion only reflects the blood supply of the affected testis, and the greater the degree of torsion, the shorter the time required to cause testicular vascular injury is needed. 20Therefore, it does not mean that the greater the degree of spermatic cord torsion is, the more serious the testicular injury is, whereas the former also needs to be combined with more factors, such as the duration of symptoms.
Hematological parameters may be used to predict testicular viability in individuals with testicular torsion.However, the outcomes are inconsistent.He et al. reported that the symptom duration, degree of spermatic cord torsion, and mean platelet volume (MPV) could all be utilized as indicators of the viability of the twisted testicles. 21In line with these findings, NLR could also be utilized as a predictor of testicular viability in patients with testicular torsion within 3-12 h, according to other research. 22Yilmaz et al. found that monocyte count was the only significant variable of testicular viability (OR, 0.046; 95% CI, 0.006-0.366;p = 0.004) in patients with testicular torsion using multivariate analysis. 23The authors noted that the monocyte count in patients with testicular torsion might indicate testicular viability.In our study, monocyte count was identified as an independent risk factor for testicular salvage during testicular torsion using multivariate logistic regression analysis (OR, 0.012; 95% CI, 0.000-0.755;p = 0.036).However, due to the limited sample size and age composition, predicting testicular vitality after testicular torsion using hematological parameters remains controversial; more prospective studies are needed to verify this.
This single-center study has several limitations.First, ultrasound is highly dependent on the operator's experience.Therefore, we only evaluated the presence of blood flow in the patients' testes and did not assess the decrease in blood flow signal and normal blood flow in details.Second, surgery in patient was not performed by the same doctor, which may have led to selective bias in judging testicular retention during surgery.Finally, the postoperative follow-up time might have been insufficient.Further follow-up observations are needed for longer-term changes in testicular volume and endocrine function.
In conclusion, this study determined the risk factors for testicular salvage after testicular torsion in our cohort.Increased symptom duration without intratesticular blood flow increased the monocyte count and spermatic cord torsion degree and decreased the success rate of testicular salvage.We constructed a nomogram based on the above factors and substituted the data of the verification cohort for ROC analysis.The AUC was 0.965 (95% CI 0.867-0.997),sensitivity was 90.5%, and specificity was 88.9%.This predictive model could provide parents and clinicians of children with testicular torsion with an exact probability based on the testicular salvage status of the child.

FIGURE 1
FIGURE 1 (a) Nomogram for the prediction of testicular salvage after testicular torsion in children.Prognostic nomograms including the duration of symptoms, intratesticular blood flow, monocyte count, and spermatic cord torsion degree.(b) Calibration plot.(c) Receiver operating characteristic (ROC) curve of the verification cohort.

FIGURE 2
FIGURE 2 (a) Receiver operating characteristic (ROC) curves of the duration of symptoms, intratesticular blood flow, monocyte count, and spermatic cord torsion degree for predicting testicular salvage.(b) ROC curve of the training cohort.

TABLE 1
Baseline characteristics of patients with testicular torsion in the training cohort.
Abbreviations: MPV, mean platelet volume; NLR, neutrophil-lymphocyte ratio; PLR, platelet-lymphocyte ratio; WBC, white blood cell.DISCUSSIONDetermining testicular viability after testicular torsion is a major challenge in clinical practice.Currently, there are few studies on prediction models of testicular torsion.Zheng et al. predicted the possibility of testicular salvation based on the duration of symptoms, testicular parenchymal echotexture, and intratesticular blood flow in patients with testicular

TABLE 2
Univariate and multivariate analysis results.

TABLE 3
Baseline characteristics of patients with testicular torsion in the verification cohort.