Outcomes of extracardiac Fontan operation: A single institution experience with 398 patients.

OBJECTIVE: The study objective was to evaluate the outcomes of the extracardiac Fontan operation at a single institution. METHODS: We conducted a retrospective study of 398 patients from a single institution who underwent their initial extracardiac Fontan operation between 1997 and 2020. We determined the incidence of and risk factors for failure of the Fontan circulation, which includes death, Fontan takedown, heart transplantation, protein-losing enteropathy, plastic bronchitis, and functional status at the last follow-up. RESULTS: The median follow-up time was 10.3 years (interquartile range, 6.4-14.6). The overall survival was 96% and 86% at 10 and 20 years after extracardiac Fontan operation, respectively. There were 6 early deaths (6/398, 1.5%) and 15 late deaths (15/398, 3.8%). Forty-nine patients (12.5%) developed failure of the Fontan circulation. Freedom from the failure of Fontan circulation was 88% at 10 years and 76% at 20 years. Risk factors for failure of the Fontan circulation were right ventricular dominance (hazard ratio, 4.7; P < .001; 95% CI, 2.1-10.5), aortic atresia (hazard ratio, 5.5; P < .001; 95% CI, 2.3-12.8), and elevated mean pulmonary artery pressure (hazard ratio, 2.3; P = .002; 95% CI, 1.2-6.7). CONCLUSIONS: Rates of failure of the Fontan circulation are low after the contemporary extracardiac Fontan operation. Risk factors for failure of the extracardiac Fontan circulation include right ventricular dominance, aortic atresia, and elevated pulmonary artery pressures.

Cognitive models for mentally visualizing a sharp instrument in a blind procedure.

Purpose: Our objective was to understand the cognitive strategies used by surgeons to mentally visualize navigation of a surgical instrument through blind space. Methods: We conducted semi-structured interviews with 15 expert and novice surgeons following simulated retropubic trocar passage on 3D-printed models of pelvises segmented from preop MRIs. Midurethral sling surgery involves blind passage of a trocar among the urethra, bladder, iliac vessels, and bowel while relying primarily on haptic feedback from the suprapubic bone (SPB) for guidance. Our conceptual foundation was based on Lahav's study on blind people's mental mapping of spaces using haptic cues. Participants detailed how they mentally pictured the trocar's location relative to vital anatomy. We coded all responses and used constant comparative analysis to generate themes, confirmed with member checking. Results: Expert and novice participants utilized multiple cognitive strategies combined with haptic feedback to accomplish safe trocar passage. Some used a step-by-step route strategy, visualizing sequential 2D axial images of anatomy adjacent to the SPB. Others used a map strategy, forming global 3D pictures. Although these mental pictures vanished when they were "lost," a safe zone could be reestablished by touching the SPB. Experts were more likely to relate their body position to the trocar path and rely on minor variations in resistance. Novices were more inclined toward backtracking of the trocar. Conclusions: Our findings may be extended to any blind surgical procedure. Teaching visualization strategies and incorporating tactile feedback can be used intraoperatively to help learners navigate their instrument safely around vital organs.

Surgeon estimation of retropubic trocar position in blind 3D space.

INTRODUCTION AND HYPOTHESIS: Retropubic midurethral sling surgery involves the blind passage of trocars near vital organs. We quantified the proximity of surgeons' mental representation of trocar position relative to actual position using a pelvis simulation platform. We hypothesized that novice surgeons, compared with experts, would estimate the trocar's location to be further from the actual location. METHODS: Novice and expert surgeons performed bilateral retropubic trocar passes of a Gynecare TVT trocar (#810041B-#810,051) on the simulation platform. We measured the trocar tip's position using a motion capture system, and recorded vocalizations when they perceived contacting the bone and crossing three landmark-oriented planes. We calculated differences (∆Bone, ∆Turn, ∆Top, ∆Pop) between vocalization times and when the trocar crossed the corresponding plane. We performed Mann-Whitney and Chi-squared tests to investigate differences between novices and experts and Levene's test to assess equality of variances for subject-level variation. RESULTS: A total of 34 trials, including 22 expert and 12 novice trials, were performed by six participants. ∆Bone was significantly smaller among novice surgeons (1.27 vs 2.81 s, p=0.013). There were no significant differences in the remaining three deltas or in vocalizing early versus late. Levene's test revealed no significant differences in within-subject variability for any of the four deltas. Novices passed the trocar anterior to the pubic bone on three passes. CONCLUSIONS: Novices were similar to expert surgeons in their estimation of the trocar's location and may have relied more heavily on anticipatory mechanisms to compensate for lack of experience. Teaching surgeons should make sure the novice surgeon trocar pass starts posterior to the bone.

Impact of Aortic Atresia After Fontan Operation in Patients With Hypoplastic Left Heart Syndrome.

BACKGROUND: Patients with aortic atresia have the worst prognosis in the spectrum of hypoplastic left heart syndrome. It remains unknown whether patients with aortic atresia continue to do poorly after Fontan operation. This study aimed to determine the association between aortic atresia and atrioventricular valve (AVV) function and clinical outcomes after Fontan operation in patients with hypoplastic left heart syndrome. METHODS: We performed a retrospective study of 1731 patients who survived the Fontan operation from the Australia and New Zealand Fontan Registry between 1975 and 2020. RESULTS: We identified 188 patients with hypoplastic left heart syndrome, including 99 (53%) with aortic atresia. Overall transplant-free survival and freedom from failure of Fontan circulation at 15 years was 91% (95% CI, 86%-96%) and 79% (95% CI, 71%-88%), respectively. The cumulative incidence of AVV operation at 15 years of age for patients with aortic atresia and aortic stenosis was 28% (95% CI, 19%-38%) and 14% (95% CI, 7%-22%; P = .03), respectively. The cumulative incidence of AVV failure (moderate or greater regurgitation or AVV operation) at 15 years of age for patients with aortic atresia and aortic stenosis was 50% (95% CI, 37%-61%) and 30% (95% CI, 19%-42%; P = .01). Patients with AVV failure were at increased risk of having moderately, or worse, decreased systolic ventricular function (odds ratio 6.7; 95% CI, 1.7-33; P = .01) and failure of Fontan circulation (hazard ratio 3.7; 95% CI, 1.5-9.1; P < .01). CONCLUSIONS: In patients with hypoplastic left heart syndrome, there is no significant difference in transplant-free survival after Fontan operation between patients with aortic atresia and patients with aortic stenosis. However, patients with aortic atresia have a much higher burden of AVV failure than patients with aortic stenosis. Atrioventricular valve failure is associated with failure of Fontan circulation.

Atrioventricular septal defect in Fontan circulation: Right ventricular dominance, not valve surgery, adversely affects survival.

OBJECTIVE: The effect of ventricular dominance and previous atrioventricular valve (AVV) surgery on patient outcomes after Fontan operation remains unclear. We sought to determine the effect of ventricular dominance and previous AVV surgery on transplantation-free survival and long-term AVV competency in patients with atrioventricular septal defect (AVSD) and Fontan circulation. METHODS: We conducted a retrospective study of 1703 patients in the Australia and New Zealand Fontan Registry, who survived Fontan operation between 1987 and 2021. RESULTS: Of 174 patients with AVSD, 60% (105/174) had right ventricular (RV) dominance and 40% (69/174) had left ventricular (LV) dominance. The cumulative incidence of moderate or greater AVV regurgitation at 25 years after Fontan operation in patients with LV dominance was 56% (95% CI, 35%-72%), compared with 54% (95% CI, 40%-67%) in patients with RV dominance (P = .6). Nonetheless, transplantation-free survival at 25 years in patients with LV dominance was 94% (95% CI, 86%-100%), compared with 67% (95% CI, 52%-87%) in patients with RV dominance (hazard ratio, 5.9; 95% CI, 1.4-25.4; P < .01). Of note, transplantation-free survival was not different in patients who underwent AVV surgery before or at Fontan completion compared with those who did not (15 years: 81% [95% CI, 62%-100%] vs 88% [95% CI, 81%-95%]; P = .3). CONCLUSIONS: In patients with AVSD and Fontan circulation the rate of moderate or greater common AVV regurgitation is similar in those with LV and RV dominance. RV dominance, rather than previous AVV surgery, is a risk factor for death or transplantation.

Retropubic trocar modified with a load cell to verify contact with pubic bone.

BACKGROUND: Vital injuries during midurethral sling surgery are avoided by maintaining constant trocar contact with bone, and yet this is challenging for a teaching surgeon to monitor during this blind procedure. We modified a retropubic trocar with a load cell to distinguish on-bone and off-bone movement and tested it on a midurethral sling surgery 3-dimensional surgery simulator. METHODS: Two experts and 3 novice surgeons performed retropubic trocar passage on the physical pelvic floor model using the modified trocar. Biofidelity was assessed comparing expert performance on a Thiel-embalmed cadaver and the physical model. The test-retest was assessed comparing performance on the physical pelvic model 2 weeks apart. The force variables were analyzed with paired and independent t tests. We performed post hoc analyses comparing the experts to novices on the physical model. RESULTS: The root-mean-squared force was similar between the cadaver and model (24.3 vs 21.1 pounds, P = .62), suggesting biofidelity. Root-mean-squared force was also similar between the test and retest (14.0 vs 19.1 pounds, P =. 30). The expert surgeons exhibited a larger maximum force amplitude (51.2 vs 22.7 pounds, P = .03), shorter time to maximum force (2.7 vs 9.5 seconds, P = .03) and larger maximum rate of force development (171.5 vs 54.0 pounds/second, P = .01). CONCLUSION: This study suggested high test-retest reliability and adequate biofidelity of the modified trocar used on our midurethral sling surgery 3-dimensional surgery simulator. This innovative trocar can be used both in simulation and in the operating room to help the novice surgeons stay on the bone and to help the attending surgeon monitor safe surgery.

Small airways dysfunction is associated with increased exacerbations in patients with asthma.

There is a poor understanding of why some patients with asthma experience recurrent exacerbations despite high levels of treatment. We compared measurements of peripheral ventilation heterogeneity and respiratory system mechanics in participants with asthma who were differentiated according to exacerbation history, to ascertain whether peripheral airway dysfunction was related to exacerbations. Three asthmatic groups: "stable" (no exacerbations for >12 mo, n = 18), "exacerbation-prone" (≥1 exacerbation requiring systemic corticosteroids within the last 12 mo, but stable for ≥1-mo, n = 9), and "treated-exacerbation" (exacerbation requiring systemic corticosteroids within the last 1 mo, n = 12) were studied. All participants were current nonsmokers with <10 pack yr smoking history. Spirometry, static lung volumes, ventilation heterogeneity from multibreath nitrogen washout (MBNW), and respiratory system mechanics from oscillometry were measured. The exacerbation-prone group compared with the stable group had slightly worse spirometry [forced expired volume in 1 s or FEV1 z-score -3.58(1.13) vs. -2.32(1.06), P = 0.03]; however, acinar ventilation heterogeneity [Sacin z-score 7.43(8.59) vs. 3.63(3.88), P = 0.006] and respiratory system reactance [Xrs cmH2O·s·L-1 -2.74(3.82) vs. -1.32(1.94), P = 0.01] were much worse in this group. The treated-exacerbation group had worse spirometry but similar small airway function, compared with the stable group. Patients with asthma who exacerbate have worse small airway function as evidenced by increases in Sacin measured by MBNW and ΔXrs from oscillometry, both markers of small airway dysfunction, compared with those that do not.NEW & NOTEWORTHY This study assessed the relationship between peripheral airway function, measured by multiple breath nitrogen washout and oscillometry impedance, and exacerbation history. We found that those with a history of exacerbation in the last year had worse peripheral airway function, whereas those recently treated for an asthma exacerbation had peripheral airway function that was comparable to the stable group. These findings implicate active peripheral airway dysfunction in the pathophysiology of an asthma exacerbation.

Relationship between concavity of the flow-volume loop and small airway measures in smokers with normal spirometry.

BACKGROUND: There is increasing evidence of small airway abnormalities in smokers despite normal spirometry. The concavity in the descending limb of the maximum expiratory flow curve (MEFV) is a recognised feature of obstruction and can provide information beyond FEV1, and potentially early smoking-related damage. We aimed to evaluate concavity measures compared to known small airway measurements. METHODS: Eighty smokers with normal spirometry had small airway function assessed: multiple breath nitrogen washout (MBNW) from which ventilation heterogeneity in the diffusion-dependent acinar (Sacin) and convection-dependent conductive (Scond) airways were assessed, and impulse oscillometry system (IOS) from which respiratory resistance and reactance at 5 Hz (R5 and X5) were measured. Concavity measures were calculated from the MEFV, partitioned into global and peripheral concavity. RESULTS: We found abnormal peripheral and global concavity as well as acinar ventilation heterogeneity are common in "normal" smokers. Concavity measures were not related to either MBNW or IOS measurements. CONCLUSION: Abnormalities in concavity indices and MBNW or oscillometry parameters are common in smokers despite normal spirometry. However, these measures likely reflect different mechanisms of peripheral airway dysfunction.

Natural and Modified History of Atrioventricular Valve Regurgitation in Patients With Fontan Circulation.

BACKGROUND: Atrioventricular valve (AVV) regurgitation is increasingly prevalent in patients with a Fontan circulation. OBJECTIVES: We sought to determine the impact of ventricular dominance and AVV operation on outcomes in patients with a Fontan circulation and ≥moderate AVV regurgitation. METHODS: We conducted a retrospective study, including propensity score matching analysis, of 1,703 patients who survived Fontan operation in Australia and New Zealand from 1987 to 2021. RESULTS: Patients undergoing AVV operation were more likely to have right ventricular (RV) dominance or an atrioventricular septal defect. In the entire cohort, death or transplantation after Fontan operation was significantly higher in patients who underwent AVV operation before or at Fontan completion compared with those who did not (20 years: 18%; 95% CI: 8%-26% vs 13%; 95% CI: 10%-15%; P = 0.03). After propensity score matching, including for RV dominance, there was no significant difference in death or transplantation between the groups (20 years: 18%; 95% CI: 8%-26% vs 16%; 95% CI: 10%-22%; P = 0.41). Only patients with RV dominance who developed ≥moderate AVV regurgitation after Fontan operation were at increased risk of death or transplantation (HR: 2.8; 95% CI: 1.4-5.3; P < 0.01). In patients with left ventricular dominance, there was no significant difference in death or transplantation between patients with ≥moderate AVV regurgitation compared with those with 

Normal limits for oscillometric bronchodilator responses and relationships with clinical factors.

INTRODUCTION: We aimed to determine normal thresholds for positive bronchodilator responses for oscillometry in an Australian general population sample aged ≥40 years, to guide clinical interpretation. We also examined relationships between bronchodilator responses and respiratory symptoms, asthma diagnosis, smoking and baseline lung function. METHODS: Subjects recruited from Sydney, Melbourne and Busselton, Australia, underwent measurements of spirometry, resistance (R rs6 ) and reactance (X rs6 ) at 6 Hz, before and after inhalation of salbutamol 200 µg. Respiratory symptoms and/or medication use, asthma diagnosis, and smoking were recorded. Threshold bronchodilator responses were defined as the fifth percentile of decrease in R rs6 and 95th percentile increase in X rs6 in a healthy subgroup. RESULTS: Of 1318 participants, 1145 (570 female) were analysed. The lower threshold for ΔR rs6 was -1.38 cmH2O·s·L-1 (-30.0% or -1.42 Z-scores) and upper threshold for ΔX rs6 was 0.57 cmH2O·s·L-1 (1.36 Z-scores). Respiratory symptoms and/or medication use, asthma diagnosis, and smoking all predicted bronchodilator response, as did baseline oscillometry and spirometry. When categorised into clinically relevant groups according to those predictors, ΔX rs6 was more sensitive than spirometry in smokers without current asthma or chronic obstructive pulmonary disease (COPD), ∼20% having a positive response. Using absolute or Z-score change provided similar prevalences of responsiveness, except in COPD, in which responsiveness measured by absolute change was twice that for Z-score. DISCUSSION: This study describes normative thresholds for bronchodilator responses in oscillometry parameters, including intra-breath parameters, as determined by absolute, relative and Z-score changes. Positive bronchodilator response by oscillometry correlated with clinical factors and baseline function, which may inform the clinical interpretation of oscillometry.

Poor Late Outcomes After Tricuspid Valve Repair in a Single Ventricle: Experience of 103 Patients.

BACKGROUND: Outcomes of tricuspid valve repair in single-ventricle palliation are poor. We sought to identify the impact of repair technique and primary mechanisms of regurgitation on outcomes after surgery. METHODS: A retrospective review of medical records across 4 centers undertaking single-ventricle palliation in Australia and New Zealand was performed. Patients with a dominant right functional single ventricle undergoing tricuspid valve repair between January 1991 and March 2019 were identified. RESULTS: One hundred three patients met inclusion criteria, with a median follow-up duration of 6.7 years (interquartile range, 1.5-12.4). Mechanism of regurgitation was structural in 30 patients, functional in 28 patients, and a combination of both in 24 patients (21 missing). Surgical repair technique consisted of annuloplasty in 42 patients, leaflet and/or subvalvular repair in 12 patients, and a combination of both in 44 patients (5 missing). Thirty-four patients died, and 5 underwent heart transplantation. Fifty-two patients experienced valve repair failure (22 re-repairs, 7 replacements, and 23 recurrent regurgitation). Of 17 patients with early valve repair failure (within 30 days of repair), 14 died. Freedom from death or transplant at 5 years after repair for patients with a successful repair was 79% (95% confidence interval, 70%-90%) compared with 15% (95% confidence interval, 6%-37%) for those with a failed repair (P < .01; hazard ratio, 8.95; 95% confidence interval, 4%-18%). CONCLUSIONS: Tricuspid valve repair failure occurs frequently in patients with a single ventricle and is associated with a significant risk of mortality. The persistence of moderate regurgitation after repair mandates reoperation.

Reduced lung elastic recoil and fixed airflow obstruction in asthma.

BACKGROUND AND OBJECTIVE: Fixed airflow obstruction (FAO) in asthma occurs despite optimal inhaled treatment and no smoking history, and remains a significant problem, particularly with increasing age and duration of asthma. Increased lung compliance and loss of lung elastic recoil has been observed in older people with asthma, but their link to FAO has not been established. We determined the relationship between abnormal lung elasticity and airflow obstruction in asthma. METHODS: Non-smoking asthmatic subjects aged >40 years, treated with 2 months of high-dose inhaled corticosteroid/long-acting beta-agonist (ICS/LABA), had FAO measured by spirometry, and respiratory system resistance at 5 Hz (Rrs5 ) and respiratory system reactance at 5 Hz (Xrs5 ) measured by forced oscillation technique. Lung compliance (K) and elastic recoil (B/A) were calculated from pressure-volume curves measured by an oesophageal balloon. Linear correlations between K and B/A, and forced expiratory volume in 1 s/forced vital capacity (FEV1 /FVC), Rrs5 and Xrs5 were assessed. RESULTS: Eighteen subjects (11 males; mean ± SD age: 64 ± 8 years, asthma duration: 39 ± 22 years) had moderate FAO measured by spirometry ((mean ± SD z-score) post-bronchodilator FEV1 : -2.2 ± 0.5, FVC: -0.7 ± 1.0, FEV1 /FVC: -2.6 ± 0.7) and by increased Rrs5 (median (IQR) z-score) 2.7 (1.9 to 3.2) and decreased Xrs5 : -4.1(-2.4 to -7.3). Lung compliance (K) was increased in 9 of 18 subjects and lung elastic recoil (B/A) reduced in 5 of 18 subjects. FEV1 /FVC correlated negatively with K (rs = -0.60, P = 0.008) and Rrs5 correlated negatively with B/A (rs = -0.52, P = 0.026), independent of age. Xrs5 did not correlate with lung elasticity indices. CONCLUSION: Increased lung compliance and loss of elastic recoil relate to airflow obstruction in older non-smoking asthmatic subjects, independent of ageing. Thus, structural lung tissue changes may contribute to persistent, steroid-resistant airflow obstruction. CLINICAL TRIAL REGISTRATION: ACTRN126150000985583 at anzctr.org.au (UTN: U1111-1156-2795).

Atrioventricular valve closure in Fontan palliation.

OBJECTIVES: Atrioventricular valve regurgitation is known to adversely impact outcomes of single-ventricle palliation, and valve repair rarely provides long-lasting results. Closure of a atrioventricular valve can sometimes be performed, but the long-term outcomes of this manoeuvre are unknown. METHODS: This retrospective study was conducted using patient data extracted from an existing bi-national, population-based registry of survivors of the Fontan procedure. RESULTS: Between January 1975 and June 2018, 1574 patients survived to hospital discharge with an intact Fontan circulation. Of these patients, 128 with a common atrioventricular valve were excluded. Thirty-eight patients underwent closure of an atrioventricular valve, and complete follow-up data were available for 36 patients. Twenty-nine patients underwent closure of the tricuspid valve and 7 patients underwent closure of the mitral valve. Seventeen patients underwent valve closure prior to Fontan, 13 patients underwent valve closure concomitant with Fontan and 6 patients underwent valve closure post-Fontan. Valve closure was performed using a patch technique in 29 cases and with direct suture in 7 cases. At the most recent echocardiography, 33 patients had no regurgitation, 2 patients had recurrent mild regurgitation and 1 patient had no echocardiographic follow-up. Six patients required reintervention post-valve closure and 7 patients required permanent pacemaker insertion post-valve closure. Freedom from reintervention at 1, 5 and 18 years post-valve closure was 86% [95% confidence interval (CI) 76-98%], 83% (95% CI 72-96%) and 83% (95% CI 72-96%), respectively. CONCLUSION: Atrioventricular valve closure is an effective surgical technique in selected patients with a single ventricle providing long-lasting competency in the majority of cases.

Reduced cognitive deficits after FLASH irradiation of whole mouse brain are associated with less hippocampal dendritic spine loss and neuroinflammation.

AIM: To evaluate the impact of ultra-rapid FLASH mouse whole brain irradiation on hippocampal dendritic spines and neuroinflammation, factors associated with cognitive impairment after brain irradiation. METHODS: We administered 30 Gy whole brain irradiation to C57BL6/J mice in sub-second (FLASH) vs. 240 s conventional delivery time keeping all other parameters constant, using a custom configured clinical linac. Ten weeks post-irradiation, we evaluated spatial and non-spatial object recognition using novel object location and object recognition testing. We measured dendritic spine density by tracing Golgi-stained hippocampal neurons and evaluated neuroinflammation by CD68 immunostaining, a marker of activated microglia, and expression of 10 pro-inflammatory cytokines using a multiplex immunoassay. RESULTS: At ten weeks post-irradiation, compared to unirradiated controls, conventional delivery time irradiation significantly impaired novel object location and recognition tasks whereas the same dose given in FLASH delivery did not. Conventional delivery time, but not FLASH, was associated with significant loss of dendritic spine density in hippocampal apical dendrites, with a similar non-significant trend in basal dendrites. Conventional delivery time was associated with significantly increased CD68-positive microglia compared to controls whereas FLASH was not. Conventional delivery time was associated with significant increases in 5 of 10 pro-inflammatory cytokines in the hippocampus (and non-significant increases in another 3), whereas FLASH was associated with smaller increases in only 3. CONCLUSION: Reduced cognitive impairment and associated neurodegeneration were observed with FLASH compared to conventional delivery time irradiation, potentially through decreased induction of neuroinflammation, suggesting a promising approach to increasing therapeutic index in radiation therapy of brain tumors.

System for Scoring Severity of Acute Radiation Syndrome Response in Rhesus Macaques (Macaca mulatta).

We developed a clinical assessment tool for use in an NHP radiation model to 1) quantify severity responses for subsyndromes of the acute radiation syndrome (ARS; that is, hematopoietic and others) and 2) identify animals that required enhanced monitoring. Our assessment tool was based primarily on the MEdical TREatment ProtocOLs for Radiation Accident Victims (METREPOL) scoring system but was adapted for NHP to include additional indices (for example, behaviors) for use in NHP studies involving limited medical intervention. Male (n = 16) and female (n = 12) rhesus macaques (Macaca mulatta; 5 groups: sham and 1.0, 3.5, 6.5, and 8.5 Gy; n = 6 per group) received sham- or bilateral 60Co γ-irradiation at approximately 0.6 Gy/mn. Clinical signs of ARS and blood analysis were obtained before and serially for clinical assessment during the period of 6 h to 60 d after sham or 60Co irradiation. Minimal supportive care (that is, supplemental nutrition, subcutaneous fluid, loperamide, acetaminophen, and topical antibiotic ointment) was prescribed based on clinical observations. Results from clinical signs and assays for assessment of relevant organ systems in individual animals were stratified into ARS severity scores of normal (0), mild (1), moderate (2), and severe (3 or 4). Individual NHP were scored for maximal subsyndrome ARS severity in multiple organ systems by using the proposed ARS scoring system to obtain an overall ARS response category. One NHP died unexpectedly. The multiple-parameter ARS severity scoring tool aided in the identification of animals in the high-dose (6.5 and 8.5 Gy) groups that required enhanced monitoring.