Abstract
Background
A comparison among X-ray-cystograms (CGs), TRUS-CGs, and no CG to determine the required indwelling time of urinary catheters after radical prostatectomy (RP).
Material and methods
We retrospectively analyzed patients who underwent robotic-assisted RP in our clinic from January 2018 to October 2022. A primary X-ray-CG was performed before the corona pandemic and a TRUS-CG was performed during the corona pandemic. The primary endpoint was the proportion of CGs needed and the proportion of catheter reinsertions.
Results
We identified 5,307 patients. Of those, 2,803 (52.8 %) did not initially receive a CG, 1643 (31 %) received an X-ray-CG and 861 (16.2 %) received a TRUS-CG. Patients who first had an X-ray-CG were most likely to receive repeated CGs (8.5 % vs. 6.7 % in TRUS patients vs. 0.2 % in patients without CG, P < 0.001). TRUS-CG and X-ray patients had the shortest catheter dwell time [in median 5d vs. 5d (X-ray) vs. 10 d (no CG), P < 0.001], whereas the rate of catheter reinsertion was higher in the TRUS-CG group [5.2 % vs. 4.2 % (X-ray) vs. 1.7 % (no CG), P < 0.001]. There was no statistically significant difference in continence one year after RP between the groups (P = 0.6).
In regression models, only operation time [odds ratio (OR):1, P = 0.001] and TRUS-CG (OR: 1.28, P = 0.003) were independent risk factors for incontinence one year after RP and X-ray-CG (OR: 2.4, P < 0.001), TRUS-CG (OR: 2.9, P < 0.001) and operation time (OR: 0.99, P = 0.005) were independent risk factors for catheter reinsertion.
Conclusion
The non-X-ray based method (TRUS-CG) could be safely used to assess the adequacy of the anastomosis, although the catheter reinsertion rate was slightly higher.
Keywords: Anastomotic leakage, Cystogram, Prostate cancer, Radical prostatectomy, Transrectal ultrasound, X-ray
1. Introduction
Radical prostatectomy (RP) is a mainstay of curative treatment of localized prostate cancer (PCa).1,2 The primary therapeutic goal, curative treatment/optimal tumour control, is followed by good functional outcomes, especially preservation of erectile function and urinary continence (UC).3 Non-influenceable factors that can lead to a reduction in surgery-associated morbidity include patient age, pathological tumour stage, prostate size, preoperative erectile function and UC as well as knowledge of important anatomical structures.4, 5, 6
Influenceable factors are the selection of the surgical approach [open RP (ORP) versus robot-assisted RP (RARP)], time of catheter removal, cigarette smoking, preservation of the bladder neck, preservation of integrity of the external urethral sphincter and preservation of a urethra as long as possible as well as nerve-sparing surgical techniques.7,8
Part of the RP is the vesico-urethral anastomosis that poses the risk of anastomotic leakage.6 This can lead to urine extravasation, urinary retention, fever, and pain. To ensure complete healing of the anastomosis and avoid complications, a urinary catheter is inserted.1 However, since a urinary catheter is also a source of infection and leads to restrictions in quality of life, it should not be left at a place longer than necessary.9 To evaluate the required length of stay, the anastomosis can be assessed postoperatively by an X-ray-cystogram (CG) or transrectal ultrasound (TRUS).1 In some clinics, a CG is performed intraoperatively to rule out leakage at an early stage.10 To date, there is little international literature comparing radiographic and TRUS-CGs to make a statement regarding the superiority of either method. In the EAU guidelines, both methods are mentioned as equivalent alternatives.1 The aim of the present study was to evaluate which CG procedure is favorable.
2. Materials and methods
2.1. Study cohort/patient population
We retrospectively identified 15,542 patients who underwent ORP or RARP for localized PCa at our tertiary care centre from January 2018 to October 2022. Exclusion criteria for further analyses were ORP, ≥2 pads daily prior to surgery, patients with an initial radiographic CG during the Corona Pandemic [CP (starting from 01/2021)] and incomplete or missing records (information about catheter removal).
Each patient received at least one CG intraoperatively. The respective surgeon determined further whether another CG was necessary and the time interval between the planned postoperative CG and RP based on the intraoperative anatomical conditions and an intraoperative leakage test with an NaCl solution via the inserted catheter.8 For logistic reasons, an X-ray-CG was performed before the CP, and a TRUS-CG was performed during the CP (Fig. 1, Fig. 2). For the TRUS, a vaginal ultrasound transducer was used instead of a standard probe to improve patient comfort and enhance compliance. Bladder was filled with a maximum of 250 ml NaCl during a TRUS-CG in order to detect leakages. Additionally, we provide a video of TRUS-CG findings (Supplement 1).
Fig. 1.
TRUS cystogram examples after radical prostatectomy. A and B: Inconspicuous TRUS findings in the sagittal plane with the inserted transurethral catheter. C: An unremarkable transverse TRUS finding with artifacts and acoustic shadows (arrow). D: A dorsal columnar hematoma as an example of an inhomogeneous, partially hypoechoic normal finding (circled). E and F: Dorsal low-echo extravasation as an expression of anastomotic insufficiency/urinoma (arrow).
TRUS, transrectal ultrasound.
Fig. 2.
Examples of an anastomotic insufficiency diagnosed via X-ray cystogram (picture in anteroposterior and Lauenstein position).
The operations were performed according to standardized procedures and using the aforementioned full functional length urethra (FFLU) technique and the neuroSAFE technique/neurovascular structure-adjacent frozen-section examination (NeuroSAFE).4,6
Data assessment was performed using our prospective institutional database (FileMaker Pro 10; FileMaker, Inc.). All patients agreed on data collection by informed consent. The study was approved by our internal review board. Standardized PROMs were used for preoperative and postoperative assessment.3
2.2. Definition of outcome variables
The evaluations focused on the event “catheter reinsertion” and the quantity of reperformed CGs. We also assessed the number of additional CGs, continence up to one year, and focused on identification of risk factors (RFs).
The date of initial diagnosis of PCa, date of Bx, UC after six month and one year after RP, initial prostate-specific antigen (PSA) level, surgical procedure, T and N stage, and number of removed lymph nodes among others were collected for each patient. These parameters were compared among the three groups: X-ray-CG (before CP) versus TRUS-CG (during CP) versus no CG.
2.3. Statistical analyses
All statistical tests were two-sided with a level of significance set at P < 0.05. Analyses were performed using the R software environment for statistical computing and graphics (version 4.1.2).11
Descriptive statistics included frequencies and proportions for categorical variables (pathological (p)T-stage, pN-stage, CG approach, for example). Means, medians [interquartile ranges (IQRs)], and ranges were reported for continuously coded variables [age, body mass index (BMI), PSA level, operation time for example]. Chi-square test was used to test for statistical significance in proportions’ differences. The t test and Kruskal–Wallis test were used to test for statistical significance of means and median differences. Univariable and multivariable logistic regression (MLR) models tested the association between incontinence one year after RP and catheter reinsertion and several variables (Supplement 2).
3. Results
In total, we analyzed 5,307 patients who underwent RARP between January 2018 and October 2022 in our tertiary care centre. Basic patient characteristics are shown in Table 1.
Table 1.
Comparison of 5,307 prostate cancer patients who received robot-assisted radical prostatectomy between January 2018 and October 2022 in a tertiary care centre with the distribution of the cystograms performed. Basic characteristics, catheter dwell time, catheter reinsertion, and number of repeated cystograms required
| Variables | Overall | No cystogram | X-ray cystogram | TRUS cystogram |
P | |
|---|---|---|---|---|---|---|
| Patients, n (%) | 5307 | 2803 (52.8) | 1643 (31) | 861 (16.2) | ||
| Age (yr) | Median (IQR) | 63 (58–68) | 63 (58–68) | 64 (59–68) | 63 (59–68) | 0.5 |
| BMI (kg/m2) | Median (IQR) | 26.5 (24.5–29) | 26.4 (24.5–29.2) | 26.5 (24.5–29.2) | 26.5 (24.5–28.7) | 0.4 |
| PSA (ng/ml) | Median (IQR) | 6.8 (4.7–10.2) | 6.8(4.7–10.4) | 7 (4.9–10.5) | 5.8 (5.8–8.7) | <0.001 |
| TRUS prostate volume (ml) | Median (IQR) | 39 (30–51) | 39 (30–50) | 39 (30–52) | 39 (30–50) | 0.004 |
| Blood loss (ml) | Median (IQR) | 200 (100–345) | 200 (100–300) | 200 (100–350) | 300 (150–400) | <0.001 |
| Operation time (min) | Median (IQR) | 160 (140–185) | 160 (140–181) | 165 (145–190) | 160 (140–183) | <0.001 |
| pT stadium, n (%) | T2 | 3526 (61.1) | 1727 (61.7) | 1014 (61.7) | 512 (60.3) | 0.5 |
| T3a | 1395 (24.2) | 666 (23.8) | 378 (23) | 222 (25.9) | ||
| ≥T3b | 847 (14.7) | 405 (14.5) | 251 (15.3) | 119 (13.9) | ||
| pN status, n (%) | NX | 1089 (18.9) | 615 (22) | 132 (8) | 229 (26.6) | <0.001 |
| N0 | 4184 (72.5) | 1947 (69.5) | 1365 (83.1) | 557 (64.7) | ||
| N1 | 501 (8.7) | 238 (8.5) | 146 (8.9) | 75 (8.7) | ||
| Gleason score, n (%) | 6 | 309 (5.4) | 155 (5.5) | 107 (6.5) | 26 (3) | 0.002 |
| 3 + 4 | 3793 (65.7) | 1849 (66.1) | 1071 (65.2) | 566 (66) | ||
| 4 + 3 | 1266 (21.9) | 620 (22.2) | 337 (20.5) | 211 (24.6) | ||
| 8–10 | 402 (7) | 175 (6.3) | 128 (7.8) | 55 (6.4) | ||
| PSM, n (%) | 1248 (21.6) | 612 (21.9) | 362 (22.1) | 172 (20) | 0.4 | |
| Number of dissected lymph nodes | Median (IQR) | 12 (5–17) | 11 (4–17) | 12 (10–14) | 12 (10–14) | 0.008 |
| PLND, n (%) | 4541 (78.6) | 2103 (75) | 1483 (90.3) | 610 (70.8) | <0.001 | |
| Hospitalization (d) | Median (IQR) | 8 (7–8) | 7 (6–8) | 8 (7–8) | 8 (7–8) | <0.001 |
| Catheter dwell time (days) | Median (IQR) | 7 (5–12) | 10 (5–12) | 5 (5–12) | 5 (5–11) | <0.001 |
| Additional cystograms, n (%) | 256 (4.4) | 7 (0.2) | 140 (8.5) | 56 (6.7) | <0.001 | |
| 1 | 127 (62) | 2 (28.6) | 83 (59.3) | 42 (72.4) | 0.1 | |
| 2 | 59 (28.8) | 3 (42.9) | 46 (32.9) | 10 (17.2) | ||
| 3 | 13 (6.3) | 1 (14.3) | 9 (6.4) | 3 (5.2) | ||
| 4 | 4 (2) | 1 (14.3) | 1 (0.7) | 2 (3.4) | ||
| 5 | 2 (1) | 0 (0) | 1 (0.7) | 1 (1.7) | ||
| Catheter reinsertion, n (%) | 191 (3.3) | 49 (1.7) | 69 (4.2) | 45 (5.2) | <0.001 | |
| Continence 1 year after surgery, n (%) | 0 | 2150 (70.9) | 1147 (69.9) | 687 (71.6) | 316 (73.1) | 0.6 |
| 1 safety pad | 508 (16.8) | 273 (16.6) | 165 (17.2) | 70 (16.2) | ||
| 1 | 208 (6.9) | 119 (7.3) | 59 (6.2) | 30 (6.9) | ||
| 2 | 110 (3.6) | 67 (4.1) | 31 (3.2) | 12 (2.8) | ||
| ≥3 | 55 (1.8) | 34 (2.1) | 17 (1.8) | 4 (0.9) |
BMI, body mass index; IQR, interquartile range; min, minute; ml, milliliter; n, number; PLND, pelvic lymph node dissection; PSA, prostate-specific antigen; PSM, positive surgical margin; TRUS, transrectal ultrasound.
A total of 2,803 (52.8 %) patients did not initially receive a CG, 1,643 (31 %) patients received an initial X-ray-CG and 861 (16.2 %) patients received an initial TRUS-CG. The median patient age was 63 years (IQR: 58–68 years) and median BMI was 26.5 kg/m2 (IQR: 24.5 kg/m2–29 kg/m2). There were no statistically significant differences among the comparison groups (no CG, X-ray-CG, and TRUS-CG; Table 1). The median blood loss was 200 ml (IQR: 100–300 ml), the median hospital stay was 8 days (IQR: 6–8 days), and the median operation time was 162 min (IQR: 142–185 min). Patients with planned TRUS-CG had the most blood loss (300 ml vs. 200 ml vs. 200 ml; P < 0.001). Patients with planned X-ray-CG had the longest operation time (165 min vs. 160 min vs. 160 min; P < 0.001). While the N1 rate hardly differed (8.5 % in no CG vs. 8.9 % in an X-ray-CG vs. 8.7 % in a TRUS-CG), there were greater differences in the NX/N0 rates (NX for example: 22 % in no CG vs. 8 % in X-ray-CG vs. 26.6 % in f-CG; P < 0.001). The rate of higher-graded Gleason scores (GSs; 8–10: 6.3 % in no CG vs. 7.8 % in X-ray-CG vs. 6.4 % in TRUS-CG; P = 0.002) was the highest in X-ray-CG patients. In 3,258 (61.5 %) patients, we found pT2, 1,266 (23.9 %) had pT3a and 775 (14.6 %) had > pT3b. Median PSA at the time of biopsy was 6.8 ng/ml (IQR: 4.7–10.2 ng/ml). Overall, 79.1 % of the patients received a pelvic lymph node dissection (PLND). Patients in the X-ray-CG group received significantly more PLND than in the other two groups (Table 1). The median number of removed lymph nodes was 12 (IQR: 10–14).
Examples of leakages in the CG are shown in Supplement 1 and Supplement 3. In total, 256 (4.4 %) patients received an additional CG. Seven of them had not initially received one, 140 (8.5 %) patients had an X-ray-CG and 58 (6.7 %) patients had a TRUS-CG before. Patients with an initial X-ray-CG received follow-up CGs more often than patients in the other two groups (8.5 % vs. 6.7 % in TRUS patients vs. 0.2 % in patients without CG, P < 0.001). Most patients (62 %) received only one additional CG procedure. The highest number of repeated CG procedures observed was five, with only 1 % of patients undergoing this maximum number. The cohort in which no CG was initially performed received significantly less additional CGs.
A new catheter, after removal, was inserted in 163 patients (3.1 %), most of them received a TRUS-CG before (5.2 % vs. 4.2 % (X-ray) vs. 1.7 % (no CG), P < 0.001).
Regarding the catheter dwell time, the median was 7 days (IQR: 5–12 days, P < 0.001). Patients with no initial CG had a median of 10 days (IQR: 5–12 days), patients of the other two groups had a median of 5 days (X-ray, IQR: 5–12 days; TRUS, IQR: 5–11 days; P < 0.001; Table 1).
With regard to continence after the 6th month, 2,134 patients (62.3 %) did not need any pad in 24h, 745 patients (21.7 %) used one safety pad and 547 patients (16 %) needed ≥1pad/24h. After 6 months, TRUS-CG patients had the best continence rates (66.1 % vs. 65.2 % in X-ray patients vs. 59.6 % in no CG patients, P = 0.003; regarding no pad). However, this statistical distinction diminished after one year (Table 1).
According to MLR, independent RFs for incontinence one year after RP (adjusted for X-ray CG, TRUS CG, age, BMI, blood loss, operation time, pT status, catheter dwell time, further CG, re-inserted catheter, nerve sparing and lymphadenectomy) were only operation time (odds ratio [OR]:1, p = 0.001) and TRUS-CG (OR: 1.28, P = 0.003; Supplement 2).
In addition, the MLR (adjusted for X-ray CG, TRUS CG, age, BMI, blood loss, operation time, pT status, catheter dwell time, nerve sparing, and lymphadenectomy) showed that X-ray-CG (OR: 2.37, P < 0.001), TRUS-CG (OR: 2.85, P < 0.001), and operative time (OR: 0.99, P = 0.005) were independent RFs for catheter reinsertion.
Furthermore, X-ray CG (OR: 46.1, P < 0.001), TRUS CG (OR: 35.7, P < 0.001), age (OR: 1.04, P = 0.001), BMI (OR: 1.06, P = 0.004), blood loss (OR: 1, P = 0.03), no nerve-sparing procedure (OR: 2.99, P < 0.001), and catheter dwell time (OR: 1, P < 0.001) were independent RFs for secondary CG.
4. Discussion
According to the current EAU guidelines, X-ray-CG and TRUS-CG are equivalent methods to detect anastomotic insufficiency after RP to estimate the required catheter indwelling time.1 The most accurate dwell time possible is important to avoid complications that may arise in case of premature as well as delayed removal. To minimize anastomotic insufficiency and optimize postoperative recovery, it is of clinical importance to determine the best method for estimating the optimal length of stay. To compare the examination methods, we focused our evaluations on the parameters “additional CG” and “renewed catheter insertion.”
Our present analyses of X-ray-CG versus TRUS-CG versus no CG demonstrated several noteworthy findings and to the best of our knowledge, this study examines the largest cohort to date. In our evaluations, more patients in the X-ray-CG group received a repeated CG than in the TRUS-CG group. This could be related to the tumour parameters which tended to perform worse in the X-ray group (Table 1). They also received more frequent intraoperative PLND. These may lead to more complicated postoperative courses which leads to higher catheter dwell time and repeated CGs. However, it should be noted that the PREDICT trial (NCT04269512) was carried out from the end of October 2019 onward, meaning that some of the intermediate risk patients did not receive PLND and a slight shift in tumour parameters during CP has already been reported by Filipas et al.12
It was also shown that a CG is not needed if the surgeon intraoperatively did not consider it necessary. This was the case for approximately half of the patients (Table 1). In this group, the catheter reinsertion rate was 1.7 % and only 0.2 % received an additional CG at all. The differences in the other two groups were statistically significant. It is crucial to bear in mind that in this scenario, there may be a selection bias as patients without initial CG may have exhibited more favorable intraoperative findings. This assertion is reinforced by the findings of James et al., whose research indicated that catheter removal after just 2 days remains safe within a meticulously chosen patient cohort as determined by intraoperative outcomes.13 In our study, the median catheter duration for patients without CG was 10 days, aligning with Guru et al.’s findings suggesting that safe catheter removal is feasible within 8–10 days without CG.14 It is worth discussing whether catheter removal could be preponed by CG guidance while achieving similar outcomes as the catheter dwell time was significantly longer in the cohort without a CG. Another reason could be the limited availability of X-ray-CGs, particularly in outpatient settings, which lead to longer waiting times for follow-up appointments and, consequently, extended catheter dwell times. In contrast, TRUS-CG can be performed in various settings and without the use of contrast agents, making it a cost-effective and widely available option. As shown in Fig. 1, TRUS also has the advantage that dorsal hematomas or perivesical lymphoceles can be detected and their extent can be described. However, foreign materials such as hemostyptic agents or intestinal gas can limit the accessibility.
Patients in the TRUS-CG cohort have had one of the shortest catheter dwell times but the highest catheter reinsertion rate (Table 1). One aspect is that patients with a TRUS-CG had significantly less PLND, suggesting a presumably smaller wound area, which could be associated with faster healing and, consequently, a shorter catheter dwell time. Consistent with this, Homer et al. identified PLND as an RF for postoperative complications, particularly in the context of RARP.15
Another reason could be that sonography is an examiner-dependent examination and is certainly subject to a certain learning curve.16 This examiner-dependent blurring does not occur to this extent in X-ray-CGs. For more difficult/inaccurate findings, the catheter could be removed too early, leading to increased reinsertions. This aligns well with the discovery that TRUS-CG serves as an RF for catheter reinsertion and for secondary CG (Supplement 2). Conversely, Eggert et al. and Cantiello et al., in their respective studies, discovered congruent results between TRUS-CG and X-ray-CG, with no instances of false-negative results reported with TRUS-CG.17,18 However, X-ray-CG was also identified as a negative RF for both outcomes in the regression models. This raises the question of whether the patient population in which a CG (X-ray or TRUS) was deemed necessary generally has a higher risk of repeated catheter insertion and the need for a second CG than the patient population which received no CG at all.
Other independent RFs for a secondary CG were age, blood loss, no nerve-sparing procedure, and catheter dwell time, though the significance is limited by the wide confidence interval. Age, blood loss, and no nerve-sparing procedure could possibly indicate a complex operation and a complicated course or more difficult circumstances. This could have led to multiple CGs or the need for additional diagnostics. In line with this, Homer et al. also identified age as an RF for postoperative complications.15 The reason for catheter dwell time as an RF could be attributed to the finding that the results of the first CG tends to prolong the length of stay, while the second CG has a controlling effect on this prolongation.
For incontinence after 1 year, especially the operation time and TRUS-CG were identified as independent RFs (Supplement 2). In TRUS-CG patients, it could be related to the higher catheter reinsertion rate. Multiple manipulation of the genitourinary tract could lead to (micro)traumata in the sphincter area, which could promote incontinence.19
The incontinence associated with the longer operation time could also be related to greater local trauma. Longer operation time suggests a more difficult surgery with a larger wound area and a higher rate of local injury.20 In addition, a reference can be made to the systemic review by Sallami, who also identified a longer duration of surgery as an RF for incontinence.21 An extended duration of surgery may also reflect a generally poorer health condition in the patient, including factors such as compromised nutritional status or cardiovascular health, which can adversely affect wound healing and potentially contribute to incontinence.20 This delayed healing process could similarly hinder the recovery of the anastomosis, necessitating a longer catheter dwell time. If the catheter is removed prematurely, before adequate healing has occurred, reinsertion might become necessary.
A further consideration pertains to the exposure to radiation. A radiographic examination of the abdomen without contrast carries an effective dose of approximately 0.5 mSv, which corresponds to 10 times the radiation exposure of a flight from Europe to the USA.22
This is comparable to the effective dose for an X-ray-CG. Given that over half of the patients necessitated an additional CG and more than a third required two, this can quickly lead to a notable cumulative radiation exposure. This risk can be reduced by using a TRUS-CG. Furthermore, TRUS-CG reduces costs cause the contrast agent is saved. Another advantage of TRUS-CG is the possibility to detect hematomas or lymphoceles close to the anastomosis which could act as a hypomochlion.
The exclusion of patients who initially underwent an X-ray-CG during the CP was an attempt to reduce potential selection bias. However, it is important to acknowledge the possibility that patients who initially underwent an X-ray or a TRUS-CG might have generally experienced worse intraoperative conditions compared to the group without an initial CG, indicating the presence of some selection bias. We used regression analyses in our analysis. In our opinion, performing multiple propensity score matchings with the three endpoints and the three clinical comparison groups would not have led to superior overall comparability than the selected models due to the reduction in the size of the subcohorts and the comparisons of different subcohorts. A further limitation results from the fact that the data originate from a high-volume centre and therefore cannot simply be generalized.
We currently have all three approaches in daily clinical practice.
5. Conclusion
Based on the results of this retrospective analysis, it can be concluded that a TRUS-CG is as reliable as an X-ray-CG for investigating the anastomosis after RP. However, it is important to note that the reliability of sonographic examinations depends heavily on the examiner. Therefore, introducing standardized protocols would be advisable to ensure consistency and accuracy. Nevertheless, it can be said that a TRUS-CG can be performed more quickly, reduces costs, and eliminates the radiation exposure for the patient compared to an X-ray-CG. Furthermore, it might be advisable to continue to use X-ray-CGs, especially in the case of difficult intraoperative conditions or poorer tumour parameters.
To be able to make more precise statements, this comparison should be examined in a randomized prospective trial.
Author contributions
Schuetz contributed to Protocol/project development, Data collection, Data analysis, and Manuscript writing/editing.
Hohenhorst contributed to Manuscript writing/editing and Video creation.
Nagaraj contributed to Manuscript writing/editing.
Graefen contributed to Protocol/project development, Data collection or management, Video editing, and Manuscript writing/editing.
Tennstedt contributed to Data collection or management and analysis.
Salomon contributed to Protocol/project development, Video editing, and Manuscript writing/editing.
Pose contributed to Protocol/project development, Data collection or management, Data analysis, Video editing, and Manuscript writing/editing.
Ethics approval, Consent to participate, Consent for publication: All patients agreed on data collection by informed consent. The study was approved by our internal review board.
Availability of data and material
Data assessment was performed using our prospective institutional database (FileMaker Pro 10; FileMaker, Inc.)
Code availability
R software environment for statistical computing was used.
Funding
Not applicable.
Conflicts of interest
There was no external financial support for this study. The authors declare that they have no conflict of interest.
Footnotes
Supplementary data to this article can be found online at https://doi.org/10.1016/j.prnil.2025.12.005.
Appendix A. Supplementary data
The following are the Supplementary data to this article:
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
Data assessment was performed using our prospective institutional database (FileMaker Pro 10; FileMaker, Inc.)