Proceedings of the Clinical Microbiology Open 2022-assessing clinical laboratory and industry responses to COVID-19 pandemic testing capacity challenges (part 1).

As the COVID-19 pandemic winds down, clinical and public health laboratories, along with industry partners, reflect on the successes and failures of the pandemic response. To capture the lessons learned and better prepare for the next pandemic, the Clinical Microbiology Open (CMO) assembled key stakeholders including directors of clinical laboratories, industry partners, and state and federal agencies such as the Centers for Disease Control and Prevention and the Food and Drug Administration. Participants were asked to provide their perspectives on the initial pandemic response, supply chain constraints especially during surges, staffing challenges, test triage and communication strategies, clinical informatics needs, laboratory financial impacts of SARS-CoV-2 testing, and the emergency use authorization process. This manuscript summarizes the diagnostic laboratory and industry perspectives on these issues that were presented and discussed at CMO and proposes some steps that could be taken to improve future pandemic responses.

Dabrafenib and trametinib in Langerhans cell histiocytosis and other histiocytic disorders.

The standard treatment for Langerhans cell histiocytosis (LCH) is chemotherapy, although the failure rates are high. Since MAP-kinase activating mutations are found in most cases, BRAF- and MEK-inhibitors have been used successfully to treat patients with refractory or relapsed disease. However, data on long-term responses in children are limited and there are no data on the use of these inhibitors as first-line therapy. We treated 34 patients (26 with LCH, 2 with juvenile xanthogranuloma, 2 with Rosai-Dorfman disease, and 4 with presumed single site-central nervous system histiocytosis) with dabrafenib and/or trametinib, either as first line or after relapse or failure of chemotherapy. Sixteen patients, aged 1.3-21 years, had disease that was recurrent or refractory to chemotherapy, nine of whom had multisystem LCH with risk-organ involvement. With a median treatment duration of 4.3 years, 15 (94%) patients have sustained favorable responses. Eighteen patients, aged 0.2-45 years, received an inhibitor as first-line treatment. All of these have had sustained favorable responses, with a median treatment duration of 2.5 years. Three patients with presumed isolated central nervous system/pituitary stalk histiocytosis had stabilization or improvement of their disease. Overall, inhibitors were well tolerated. Five patients with single-system LCH discontinued therapy and remain off therapy without recurrence. In contrast, all four patients with multisystem disease who discontinued therapy had to restart treatment. Our data suggest that children suffering from histiocytoses can be treated safely and effectively with dabrafenib or trametinib. Additional studies are, however, needed to determine the long-term safety and optimal duration of therapy.

Reduced count pediatric whole-body 18F-FDG PET imaging reconstruction with a Bayesian penalized likelihood algorithm.

BACKGROUND: Advanced positron emission tomography (PET) image reconstruction methods promise to allow optimized PET/CT protocols with improved image quality, decreased administered activity and/or acquisition times. OBJECTIVE: To evaluate the impact of reducing counts (simulating reduced acquisition time) in block sequential regularized expectation maximization (BSREM) reconstructed pediatric whole-body 18F-fluorodeoxyglucose (FDG) PET images, and to compare BSERM with ordered-subset expectation maximization (OSEM) reconstructed reduced-count images. MATERIALS AND METHODS: Twenty children (16 male) underwent clinical whole-body 18F-FDG PET/CT examinations using a 25-cm axial field-of-view (FOV) digital PET/CT system at 90 s per bed (s/bed) with BSREM reconstruction (ß=700). Reduced count simulations with varied BSREM ß levels were generated from list-mode data: 60 s/bed, ß=800; 50 s/bed, ß=900; 40 s/bed, ß=1000; and 30 s/bed, ß=1300. In addition, a single OSEM reconstruction was created at 60 s/bed based on prior literature. Qualitative (Likert scores) and quantitative (standardized uptake value [SUV]) analyses were performed to evaluate image quality and quantitation across simulated reconstructions. RESULTS: The mean patient age was 9.0 ± 5.5 (SD) years, mean weight was 38.5 ± 24.5 kg, and mean administered 18F-FDG activity was 4.5 ± 0.7 (SD) MBq/kg. Between BSREM reconstructions, no qualitative measure showed a significant difference versus the 90 s/bed ß=700 standard (all P>0.05). SUVmax values for lesions were significantly lower from 90 s/bed, ß=700 only at a simulated acquisition time of 30 s/bed, ß=1300 (P=0.001). In a side-by-side comparison of BSREM versus OSEM reconstructions, 40 s/bed, ß=1000 images were generally preferred over 60 s/bed TOF OSEM images. CONCLUSION: In children who undergo whole-body 18F-FDG PET/CT on a 25-cm FOV digital PET/CT scanner, reductions in acquisition time or, by corollary, administered radiopharmaceutical activity of >50% from a clinical standard of 90 s/bed may be possible while maintaining diagnostic quality when a BSREM reconstruction algorithm is used.

Radioiodine treatment of pediatric Graves disease: a multicenter review.

BACKGROUND: There is no standardized approach to iodine-131 (I-131) therapy of hyperthyroidism in pediatric Graves disease. This prevents systematic study of outcomes. OBJECTIVE: To characterize current radioiodine dosing and define therapeutic outcomes at multiple institutions that use ultrasound to measure thyroid size to guide I-131 ablation of Graves disease. MATERIALS AND METHODS: This was a retrospective cohort study conducted at three institutions. The three sites collected demographic data, thyroid volume measured by ultrasound (mL), pre-ablation radioiodine uptake, I-131 activity administered, and outcomes at 6 and 12 months for children younger than 18 years of age treated with I-131 between November 2004 and October 2019. Comparisons of continuous variables were performed using the Mann-Whitney U test. RESULTS: Sixty-nine patients (mean age: 14.5±2.5 years) were included, 59 (85.5%) of whom were female. The mean administered I-131 radioiodine activity was 12.5 mCi (463 MBq) (range: 3.8-29.9 mCi [141-1,106 MBq]). At 6 months post-ablation, 54 (80.5% of 67) patients were hypothyroid, 8 (11.9% of 67) were euthyroid and 5 were hyperthyroid. Two of the five hyperthyroid patients had become euthyroid at 12 months. At 12 months, 1 previously euthyroid patient was hyperthyroid. Administered activity per mL of thyroid tissue adjusted for 24-h uptake was lower (0.18 mCi [6.7 MBq] x %/mL vs. 0.31 mCi [11.5 MBq] x %/mL, P=0.0054) for patients who remained hyperthyroid at 6 months. CONCLUSION: There is substantial variability in administered activity for radioiodine ablation of Graves disease in children. Efforts to standardize practice should start by standardizing administered activity guided by measurement of thyroid size by ultrasound. Our results and those of previous studies suggest the need for administered activities ≥0.25 mCi [9.3 MBq] x %/mL of thyroid tissue.

Imaging of pediatric neuroblastoma: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper.

Neuroblastoma is the most common extracranial solid neoplasm in children. This manuscript provides consensus-based imaging recommendations for pediatric neuroblastoma patients at diagnosis and during follow-up.

Imaging of pediatric bone tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper.

Malignant primary bone tumors are uncommon in the pediatric population, accounting for 3%-5% of all pediatric malignancies. Osteosarcoma and Ewing sarcoma comprise 90% of malignant primary bone tumors in children and adolescents. This paper provides consensus-based recommendations for imaging in children with osteosarcoma and Ewing sarcoma at diagnosis, during therapy, and after therapy.

Ultrasound determination of pediatric thyroid mass.

BACKGROUND: Radioiodine therapy for Graves disease can be achieved with dosing based on estimated thyroid gland mass. Thyroid mass can be estimated using linear ultrasound measurements, and conversion factors for volume and density. The choice of conversion factors could impact estimated thyroid mass and thus administered radioiodine dose. OBJECTIVE: The objective of this study was to define the relationship between thyroid mass estimated by ultrasound and measured thyroid mass following thyroidectomy. MATERIALS AND METHODS: This was a retrospective, exempt study that included patients < 18 years of age with < 6 months between thyroid ultrasound and thyroidectomy January 2010-June 2020. Thyroid dimensions by ultrasound, thyroid mass at thyroidectomy and histopathological diagnosis were collected. Published conversion factors were used to estimate thyroid volume with conversion to mass using a density of 1.05 g/cm3. Pearson correlations and Bland-Altman difference analyses were used to define the relationship between estimated mass and specimen weight. Linear regression was used to calculate an optimal conversion factor for estimating thyroid mass. RESULTS: We included 86 patients, 67 female (78%), with a mean age of 14.5 ± 3.15 years. Mass estimated using all tested conversion factors had similar strong, positive correlation with specimen weight (r = 0.95). The mean difference between thyroid mass estimated by ultrasound and measured mass ranged from - 0.34 g (conversion factor = 0.523) to 1.69 g (conversion factor = 0.554). The optimal simplified factor for estimation of thyroid mass for the study sample was 0.537. CONCLUSION: All published conversion factors for estimating thyroid mass based on linear ultrasound measurements produce good estimates of thyroid mass. Errors in estimated mass are less than 2 g on average.

Simulated Reduced-Count Whole-Body FDG PET: Evaluation in Children and Young Adults Imaged on a Digital PET Scanner.

BACKGROUND. Digital PET scanners with increased sensitivity may allow shorter scan acquisition times or reductions in administered radiopharmaceutical activities. OBJECTIVE. The purpose of this study was to evaluate in children and young adults the impact of shorter simulated acquisition times on the quality of whole-body FDG PET images obtained using a digital PET/CT system. METHODS. This retrospective study included 27 children and young adults (nine male and 18 female patients) who underwent clinically indicated whole-body FDG PET/CT examinations performed using a 25-cm axial FOV PET/CT system at 90 s per bed position (expressed hereafter as seconds per bed). Raw list-mode data were reprocessed to simulate acquisition times of 60, 55, 50, 45, 40, and 30 s/bed. Three radiologists independently reviewed reconstructed images and assigned Likert scores for lesion conspicuity, normal structure conspicuity, image quality, and image noise. A separate observer recorded the SUVmax, SUVmean, and SD of the SUV (SUVSD) for liver, thigh, and the most FDG-avid lesion. The SUVSD/SUVmean (the SUVSD divided by the SUVmean) was calculated as a surrogate of image noise. ANOVA, the Friedman test, and the Dunn test were used to compare qualitative measures (combining reader scores) and SUV measurements. RESULTS. The mean patient age was 10.8 ± 8.3 (SD) years, mean BMI was 18.7 ± 2.9, and mean administered FDG activity was 4.44 ± 0.37 MBq/kg (0.12 ± 0.01 mCi/kg). No qualitative measure showed a significant difference versus 90 s/bed for the simulated acquisition at 60 s/bed (all p > .05). Significant differences (all p < .05) versus 90 s/bed were observed for lesion conspicuity at at most 40 s/bed, conspicuity of normal structures and overall image quality at at most 45 s/bed, and image noise at at most 55 s/bed. SUVmean was not significantly different from 90 s/bed for any site for any reduced-count simulation (all p > .05). SUVSD/SUVmean and SUVmax showed gradual increases with decreasing acquisition times and were significantly different from 90 s/bed only for liver at 60 s/bed (for SUVmax: 1.00 ± 0.00 vs 1.05 ± 0.03, p = .02; for SUVSD/SUVmean: 0.09 ± 0.02 vs 0.11 ± 0.02, p = .04). CONCLUSION. Favorable findings for the simulated acquisition at 60 s/bed suggest that, in children and young adults who undergo imaging performed using a 25-cm FOV digital PET scanner, acquisition time or administered FDG activity may be decreased by approximately 33% from the clinical standard without significantly impacting image quality. CLINICAL IMPACT. A 25-cm axial FOV digital scanner may allow FDG PET/CT examinations to be performed with reduced radiation exposure or faster scan acquisition times.

Agreement between serum estimates of glomerular filtration rate (GFR) and a reference standard of radioisotopic GFR in children with cancer.

BACKGROUND: Accurate assessment of renal function is important in the care of children with cancer because renal function has implications for anti-tumor medication dosing and eligibility for clinical trials. OBJECTIVE: To characterize agreement between serum estimates of glomerular filtration rate (GFR) and a reference standard of radioisotopic GFR in a large pediatric oncology cohort. MATERIALS AND METHODS: We conducted a retrospective cross-sectional study of children who had both radioisotopic GFR (99mTc-diethylenetriaminepentaacetic acid, or 99mTc-DTPA) and serum labs (creatinine, cystatin C) obtained <7 days apart between January 2017 and August 2019. We calculated estimated GFR from serum labs using published equations and calculated agreement using intraclass correlation coefficient (ICC) and Bland-Altman analysis with univariate regression to define predictors of agreement. RESULTS: We included 272 pairs of data. Mean patient age was (mean ± standard deviation) 7.8±5.7 years. Mean radioisotopic GFR was 112±33 mL/min/1.73 m2. Absolute agreement between radioisotopic GFR and serum estimates was only fair (ICC=0.46-0.58) with a mean difference of -26.6 to +0.12 mL/min/1.73 m2. For radioisotopic GFR measurements <60 mL/min/1.73 m2, mean differences were greater, with serum estimates overestimating GFR by a mean of 21.5-39.6 mL/min/1.73 m2. In multivariable modeling, significant predictors of agreement included age, height, acute kidney injury and tumor type. Sensitivity of serum estimates was 14-29% for a GFR <60 mL/min/1.73 m2. CONCLUSION: Agreement between radioisotopic GFR and serum estimates of GFR is only fair and serum estimates of GFR have poor sensitivity for clinically relevant GFR <60 mL/min/1.73 m2. Radioisotopic measurement of GFR likely remains necessary to assess renal function in pediatric oncology patients with decreased renal function.

Evaluation of Antimicrobial Susceptibility Testing Methods for Burkholderia cenocepacia and Burkholderia multivorans Isolates from Cystic Fibrosis Patients.

The Burkholderia cepacia complex (BCC) is known for causing serious lung infections in people with cystic fibrosis (CF). These infections can require lung transplantation, eligibility for which may be guided by antimicrobial susceptibility testing (AST). While the Clinical and Laboratory Standards Institute recommends AST for BCC, the European Committee on Antimicrobial Susceptibility Testing (EUCAST) does not, due to poor method performance and correlation with clinical outcomes. Furthermore, limited data exist on the performance of automated AST methods for BCC. To address these issues, reproducibility and accuracy were evaluated for disk diffusion (DD), broth microdilution (BMD), and MicroScan WalkAway using 50 B. cenocepacia and 50 B. multivorans isolates collected from people with CF. The following drugs were evaluated in triplicate: chloramphenicol (CAM), ceftazidime (CAZ), meropenem (MEM), trimethoprim-sulfamethoxazole (TMP-SMX), minocycline (MIN), levofloxacin (LVX), ciprofloxacin (CIP), and piperacillin-tazobactam (PIP-TAZ). BMD reproducibility was ≥ 95% for MEM and MIN only, and MicroScan WalkAway reproducibility was similar to BMD. DD reproducibility was < 90% for all drugs tested when a 3 mm cut-off was applied. When comparing the accuracy of DD to BMD, only MEM met all acceptance criteria. TMP-SMX and LVX had high minor errors, CAZ had unacceptable very major errors (VME), and MIN, PIP-TAZ, and CIP had both unacceptable minor errors and VMEs. For MicroScan WalkAway, no drugs met acceptance criteria. Analyses also showed that errors were not attributed to one species. In general, our data agree with EUCAST recommendations.

Artificial Intelligence Algorithm Improves Radiologist Performance in Skeletal Age Assessment: A Prospective Multicenter Randomized Controlled Trial.

Background Previous studies suggest that use of artificial intelligence (AI) algorithms as diagnostic aids may improve the quality of skeletal age assessment, though these studies lack evidence from clinical practice. Purpose To compare the accuracy and interpretation time of skeletal age assessment on hand radiograph examinations with and without the use of an AI algorithm as a diagnostic aid. Materials and Methods In this prospective randomized controlled trial, the accuracy of skeletal age assessment on hand radiograph examinations was performed with (n = 792) and without (n = 739) the AI algorithm as a diagnostic aid. For examinations with the AI algorithm, the radiologist was shown the AI interpretation as part of their routine clinical work and was permitted to accept or modify it. Hand radiographs were interpreted by 93 radiologists from six centers. The primary efficacy outcome was the mean absolute difference between the skeletal age dictated into the radiologists' signed report and the average interpretation of a panel of four radiologists not using a diagnostic aid. The secondary outcome was the interpretation time. A linear mixed-effects regression model with random center- and radiologist-level effects was used to compare the two experimental groups. Results Overall mean absolute difference was lower when radiologists used the AI algorithm compared with when they did not (5.36 months vs 5.95 months; P = .04). The proportions at which the absolute difference exceeded 12 months (9.3% vs 13.0%, P = .02) and 24 months (0.5% vs 1.8%, P = .02) were lower with the AI algorithm than without it. Median radiologist interpretation time was lower with the AI algorithm than without it (102 seconds vs 142 seconds, P = .001). Conclusion Use of an artificial intelligence algorithm improved skeletal age assessment accuracy and reduced interpretation times for radiologists, although differences were observed between centers. Clinical trial registration no. NCT03530098 © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Rubin in this issue.

Clinical Laboratory Perspective on Streptococcus halichoeri, an Unusual Nonhemolytic, Lancefield Group B Streptococcus Causing Human Infections.

Streptococcus halichoeri is a relatively newly identified species of pyogenic streptococci that causes zoonotic infection in humans. S. halichoeri was first described in 2004 as indigenous to seals, and only 8 reports of human S. halichoeri infection have been published. S. halichoeri grows as small, white, nonhemolytic colonies and may be strongly catalase-positive on routine blood agar media, which can lead to isolates being misidentified as coagulase-negative staphylococci. S. halichoeri tests positive for Lancefield group B antigen, like S. agalactiae, but can be identified with matrix-assisted laser desorption/ionization time of flight mass spectrometry or partial 16S rRNA sequencing. We describe 3 cases of S. halichoeri bone and joint infections in patients in the United States with underlying health conditions. In addition, we examine the microbiologic characteristics of S. halichoeri and discuss the importance of fully identifying this organism that might otherwise be disregarded as a skin commensal.

Prognostic significance of pretreatment 18F-FDG positron emission tomography/computed tomography in pediatric neuroblastoma.

BACKGROUND: 18F-2-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) shows tumor activity in most neuroblastomas, but the role of 18F-FDG PET/CT in neuroblastoma remains to be defined. OBJECTIVE: This study explored the prognostic significance of 18F-FDG PET in newly diagnosed neuroblastic tumors. MATERIALS AND METHODS: This retrospective study reviewed all 18F-FDG PET/CT examinations performed for a new diagnosis of suspected neuroblastoma. MYCN amplification status, tumor recurrence and survival were abstracted from the medical record. Primary tumors were manually segmented to measure maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), tumor volume and total lesion glycolysis. Univariate and multivariable analyses using Cox proportional hazards regression testing assessed the predictive performance of PET indices for event-free survival and overall survival with thresholds determined using receiver operating characteristic curve analysis. RESULTS: Fifty-five children were included, with a median age of 2.9 years (interquartile range [IQR] 1.8-3.0 years). SUVmax, tumor volume and total lesion glycolysis were higher in MYCN-amplified tumors (P=0.012, P<0.0001, P<0.0001, respectively) and in higher International Neuroblastoma Risk Group (INRG) stages (P=0.0008, P=0.0017, P=0.0017, respectively). After adjusting for age, tumor SUVmax (P=0.028) and SUVmean (P=0.045) were associated with overall survival. An SUVmax threshold of 4.77 (P=0.028) best predicted overall survival, with median overall survival of 2,604 days (SUVmax>4.77) vs. >2,957 days (SUVmax≤4.77). No PET parameters were independently significantly associated with overall survival or event-free survival after controlling for MYCN status, stage or treatment risk stratification. CONCLUSION: Tumor metabolic activity is higher in higher-stage MYCN-amplified neuroblastic tumors. Higher SUVmax and SUVmean were associated with worse overall survival but were not independent of other prognostic markers.

Discrepancies between F-18-FDG PET/CT findings and conventional imaging in Langerhans cell histiocytosis.

BACKGROUND: Accurate risk stratification of Langerhans cell histiocytosis (LCH) is essential as management can range from conservative in single system, low risk for central nervous system (CNS) involvement lesions to intensive chemotherapy for multisystem or high-risk disease. Additionally, being able to differentiate metabolically active from inactive lesions is essential for both prognostic reasons and to avoid potentially unnecessary treatment. METHODS: A retrospective review was performed on all patients with histopathology-confirmed LCH at Cincinnati Children's Hospital Medical Center (CCHMC) between 2009 and 2019. RESULTS: One hundred seven positron emission tomography (PET)/computerized tomography (CT) images were included in the review. A discrepancy between PET/CT and conventional imaging occurred on 53 occasions. On 13 occasions, increased uptake was observed on PET in an area with no identifiable lesion on conventional imaging. On 40 occasions, lesions were found on conventional imaging where no increased uptake was observed on PET. On eight skeletal surveys, three other radiographs, four diagnostic CTs, five localization CTs, and one bone scan, no lesion was identified in an area with increased fluorodeoxyglucose (FDG) uptake. This occurred exclusively in bone. On nine skeletal surveys, one other radiograph, four diagnostic CTs, six localization CTs, 19 magnetic resonance imaging (MRI) scans, and one bone scan, a lesion was identified in a location without increased FDG uptake. This occurred in bone, CNS, and lungs. CONCLUSION: F-18-FDG PET/CT is vital in the evaluation of LCH lesions given its ability to detect LCH lesions not detectable on conventional imaging modalities, as well as its ability to distinguish metabolically active from inactive disease. MRI and diagnostic CT are still useful adjunctive tests for identification of CNS and lung lesions.

Childhood Adversity and Intimate Partner Violence in Adulthood: The Mediating Influence of PTSD in a Sample of Women Prisoners.

Although past research documents strong linkages between adverse childhood experiences (ACEs), posttraumatic stress disorder (PTSD), and adult intimate partner violence (IPV) in the lives of women prisoners, researchers have often neglected to consider the potential mediating role of PTSD in the relationships between ACEs and adult IPV. Using data from a stratified random sample of all incarcerated women in Oklahoma (N = 334), we explore the relationships between ACEs, PTSD symptomology, and adult IPV utilizing a feminist life course theoretical framework. Results indicate that PTSD symptomology fully mediates the relationship between ACEs and adult IPV, suggesting that PTSD may be central to understanding pathways to adult IPV as well as offending and incarceration for women. Implications and suggestions for policy and future research are offered.

Native American and Non-Native American Women Prisoners, Adverse Childhood Experiences, and the Perpetration of Physical Violence in Adult Intimate Relationships.

Native American women are at an especially high risk of lifetime violence, including childhood abuse, intimate partner violence (IPV), and sexual assault, and are overrepresented in the criminal justice system. Yet few studies have examined how the long-term effects of child maltreatment and other adverse childhood experiences (ACEs) affect Native American women prisoners' perpetration of physical violence in adult intimate relationships. This is surprising because ample research illustrates that childhood adverse events, particularly childhood abuse and neglect, have far-reaching effects across the life course and that these experiences are especially apparent in the lives of women involved in the criminal justice system. Using data from a stratified random sample of Native American (n = 92) and non-Native American (n = 264) women prisoners in Oklahoma, we explore the relationships between individual, cumulative, and clusters of ACEs as they relate to the use of physical violence in adult intimate relationships. Utilizing a feminist life course theoretical framework, our findings indicate that ACEs are not only critical to understanding adult IPV but also that the mechanisms and processes underlying the relationships between ACEs and the perpetration of physical violence in adult intimate relationships differ for Native American and non-Native American women. The findings of the current study demonstrate that it is imperative that prison programming includes trauma-informed and trauma-specific interventions targeting Native Americans.

Childhood adversity, mental health, and the perpetration of physical violence in the adult intimate relationships of women prisoners: A life course approach.

BACKGROUND: Adverse childhood experiences (ACEs) are common, with nearly two-thirds of adult samples reporting exposure to at least one and one-quarter reporting exposure to three or more distinct types of ACEs. ACEs have been linked to various negative outcomes across the life course, including mental health problems, and the perpetration of physical violence in intimate relationships. However, little is known about the relationships between ACEs, PTSD symptomology, and use of physical violence against an adult intimate partner among incarcerated women. OBJECTIVE: The purpose of this paper is to examine the relationships between ACEs, PTSD symptoms, and the perpetration of the physical violence in the adult intimate relationships of women prisoners. METHODS: Using data from the 2014 Oklahoma Study of Incarcerated Mothers and Their Children (N = 349) and structural equation modeling (SEM) techniques, we investigate the potential mediating effect of PTSD symptoms in the relationship between ACEs and perpetrating violence against an intimate partner. RESULTS: Our findings indicate that PTSD symptomology fully mediates the relationship between ACEs and the perpetration of physical violence against an adult intimate partner, indicating that PTSD experiences may be central to understanding women's pathways toward violence. CONCLUSIONS: Women prisoners who were exposed to ACEs during childhood were at a particularly elevated risk of developing PTSD symptomology and perpetrating physical violence against an adult intimate partner. Based on the current study's findings, treatment programs that address these complex relationships between ACEs, particularly focusing on the central role of mental health in these processes, are needed for incarcerated women.