Prospective Evaluation of Circulating Tumor DNA using Next Generation Sequencing as a Biomarker during Neoadjuvant Chemotherapy in Localized Pancreatic Cancer.

OBJECTIVE: In this prospective study, we aim to characterize the prognostic value of circulating tumor DNA (ctDNA) by next-generation-sequencing (NGS) in patients undergoing neoadjuvant chemotherapy (NAC) for pancreatic ductal adenocarcinoma (PDAC). SUMMARY BACKGROUND DATA: Circulating tumor DNA is a promising blood-based biomarker that is prognostic in several malignancies. Detection of ctDNA by NGS may provide insights regarding the mutational profiles in PDAC to help guide clinical decisions for patients in a potentially curative setting. However, the utility of ctDNA as a biomarker in localized PDAC remains unclear. METHODS: Patients with localized PDAC were enrolled in a prospective study at Northwestern Medicine between October 2020 and October 2022. Blood samples were collected to perform targeted tumor agnostic NGS utilizing the Tempus x|F 105 gene panel at three timepoints: pre-therapy (at diagnosis), post-NAC, and after local therapy, including surgery. The relationship between ctDNA detection and CA19-9, and the prognostic significance of ctDNA detection were analyzed. RESULTS: 56 patients were included in the analysis. ctDNA was detectable in 48% at diagnosis, 33% post-NAC, and 41% after local therapy. After completion of NAC, patients with detectable ctDNA had higher CA19-9 levels versus those without (78.4 vs. 30.0, P=0.02). The presence of baseline ctDNA was associated with a CA19-9 response; those without ctDNA had a significant CA19-9 response following NAC (109.0 U/mL vs. 31.5 U/mL; P=0.01), while those with ctDNA present at diagnosis did not (198.1 U/mL vs. 113.8 U/mL; P=0.77). In patients treated with NAC, the presence of KRAS ctDNA at diagnosis was associated with and independently predicted worse progression-free-survival. CONCLUSION: This report demonstrates the prognostic value of ctDNA analysis with NGS in localized PDAC. NGS ctDNA is a biomarker of treatment response to NAC. KRAS ctDNA at diagnosis independently predicts worse survival in patients treated with NAC.

Immunosurveillance associated with upper respiratory symptoms in elite swimmers: The 8-month period leading into Commonwealth Games.

OBJECTIVES: To monitor individual mucosal immunity and identify potential risk factors of upper respiratory symptoms in elite swimmers over a competitive season. DESIGN: Eight-month longitudinal study, observing mucosal immunity, Epstein-Barr virus status, training loads and illness symptoms of elite international swimmers, leading into the Commonwealth Games 2018. METHODS: Participants were fourteen elite swimmers (age ±â€¯standard deviation = 19.9 ±â€¯0.8 years, height = 178.9 ±â€¯6.3 cm, and mass = 75.0 ±â€¯7.7 kg). Self-reported upper respiratory symptoms, training load and saliva samples were collected weekly. Venous blood samples were taken at study commencement to determine Epstein-Barr virus status. RESULTS: Throughout the study, 70 episodes of upper respiratory symptoms were recorded resulting in 34 days of missed training. Incidence (p = 0.001), severity (p = 0.022), and duration of upper respiratory symptoms (p = 0.001) were significantly higher during high training loads, compared to low. Eight swimmers (61 %) had evidence of past infection with Epstein-Barr virus, but this had no relationship with incidence, severity, or duration of upper respiratory symptoms (p > 0.05). Relative individual salivary immunoglobulin A concentration was 12 % lower when upper respiratory symptoms were present but was not statistically significant (p = 0.101). CONCLUSIONS: This study highlights the importance of individual athlete monitoring, to identify swimmers at increased illness risk. Identification of possible risk factors for upper respiratory symptoms, such as increased training load, may allow for modifications in training or other illness preventative strategies for elite swimmers.

Weight loss during neoadjuvant chemotherapy impacts perioperative outcomes in patients undergoing surgery for pancreatic cancer.

BACKGROUND: While use of neoadjuvant chemotherapy (NAC) in pancreatic adenocarcinoma (PDAC) downstages cancers to be eligible for resection, weight loss during the neoadjuvant period due to cancer progression, gastric outlet obstruction, or neoadjuvant therapy itself is an area of concern. The goal of this study is to determine the effect of weight loss during NAC on perioperative outcomes of pancreatectomies. METHODS: The NSQIP database 2014-2019 was utilized to study patients who received NAC for PDAC and underwent significant weight loss, defined as at least 10 % body weight loss in the six months prior to surgery. Univariate and multivariate analyses were conducted using Fisher's Exact Test, Pearson's Chi-squared Test, and logistic regression. RESULTS: Of the 5590 PDAC patients who received NAC, 913 (16%) experienced significant weight loss. Patients who experienced significant weight loss were more likely to experience at least one complication compared to those who did not undergo weight loss (42.2% vs. 38.7%, p = 0.023). Those who had significant weight loss were more likely to undergo unplanned intubation postoperatively (3.8% vs 2.2 %, p = 0.004), have postoperative ventilator need >48 h (3.7% vs 1.8%, p < 0.001), have postoperative septic shock (3.9% vs 1.8 %, p < 0.001), and undergo reoperation (6.0% vs 4.3%, p = 0.027). However, there were no differences for pancreatic fistula (7.7% vs 9.3 %, p = 0.15), readmission rates (15% vs 15 %, p = 0.7), or 30-day mortality (1.5% vs 1.2%, p = 0.5). Utilizing logistic regression, BMI (OR: 1.05, p = 0.032), significant weight loss (OR = 1.18, p = 0.025), sex (OR = 1.26 with female baseline, p < 0.001), history of COPD (OR = 1.39, p = 0.012), hypertensive medication use (OR = 1.18, p = 0.004), and pancreatic radiotherapy (OR = 1.16, p = 0.010) were independent preoperative predictors of a post-operative complication. CONCLUSIONS: Nutritional measures to stabilize weight during NAC should be considered to decrease post-pancreatectomy complications.

The differential effect of neoadjuvant chemotherapy and chemoradiation on nodal downstaging in pancreatic adenocarcinoma.

BACKGROUND/OBJECTIVES: Neoadjuvant chemotherapy (NCT) and chemoradiotherapy (NCRT) enhance resectability in patients with pancreatic adenocarcinoma (PDAC). This study compares the effect of NCT and NCRT on lymph nodal downstaging and survival. METHODS: The 2004-2016 National Cancer Database Pancreas Participant User File was used to identify patients who underwent surgery for PDAC. Fisher's exact, Wilcoxon rank-sum, multivariate logistic regression, and log-rank were used. Downstaging was defined as clinically node-positive patients who demonstrated node-negativity on pathology. RESULTS: Of 42,545 patients meeting criteria, 3311 received NCT and 1511 received NCRT. After surgery for clinically node-positive disease, 23.3% of NCT patients and 41.3% of NCRT patients demonstrated nodal downstaging. Younger age and lower tumor grade independently predicted downstaging. Downstaging after neoadjuvant therapy was associated with improved survival versus no nodal treatment response (29.8 vs. 22.8 months, p < 0.001). Downstaging by NCT was associated with improved overall survival versus downstaging by NCRT (37.5 vs. 26.6 months, p = 0.001). No survival difference existed between those with no nodal response after NCT or NCRT (p = 0.101). CONCLUSIONS: Although nodal downstaging is more likely post-NCRT, survival is superior in those downstaged post-NCT. Overall survival is determined by the systemic burden of disease. Post-therapy histologic analysis may be less prognostic post-NCRT.

Prevalence and Spatial Distribution of Gastroschisis in an Industrial Watershed.

The relationship between the congenital defect of gastroschisis and environmental toxins is poorly understood. We examined gastroschisis incidence, risk factors, and spatial association in a geographic region with known environmental pollution and hazardous waste sites. An observational study of fetal and neonatal gastroschisis diagnosed from 1/1/2006 to 12/31/2020 was conducted in a southern West Virginia (WV) tertiary care hospital. Emerging hot spot analysis and Ripley's K-Function examined the spatial relationship between gastroschisis cases and Environmental Protection Agency (EPA) Federal Registry Sites (FRS). A total of 63 gastroschisis cases provided a prevalence rate of 14.6 per 10000 live births. Gastroschisis was associated with younger maternal age, decreased pre-pregnancy BMI, and increased maternal tobacco use. Relative to FRS sites, spatial clusters were identified with emerging hot spot analysis. Observed Ripley K was higher at all measured bands. Results suggest a potential geographic association between gastroschisis cases and EPA-designated hazardous waste sites.

The inaccuracies of gastric adenocarcinoma clinical staging and its predictive factors.

INTRODUCTION: Accurate clinical staging (CS) of gastric adenocarcinoma is important to guide treatment planning. Our objectives were to (1) assess clinical to pathologic stage migration patterns for patients with gastric adenocarcinoma, (2) identify factors associated with inaccurate CS, and (3) evaluate the association of understaging with survival. METHODS: The National Cancer Database was queried for patients who underwent upfront resection for stage I-III gastric adenocarcinoma. Multivariable logistic regression was used to detect factors associated with inaccurate understaging. Kaplan-Meier analyses and cox proportional hazards regression were performed to assess overall survival (OS) for patients with inaccurate CS. RESULTS: Of 14 425 analyzed patients, 5781 (40.1%) patients were inaccurately staged. Factors associated with understaging included treatment at a Comprehensive Community Cancer Program, presence of lymphovascular invasion, moderate to poor differentiation, large tumor size, and T2 disease. Based on overall CS, median OS was 51.0 months for accurately staged patients and 29.5 months for understaged patients (<0.001). CONCLUSION: Clinical T-category, large tumor size, and worse histologic features lead to inaccurate CS for gastric adenocarcinoma, impacting OS. Improvements to staging parameters and diagnostic modalities focusing on these factors may improve prognostication.

Impact of Skin Biopsy and Clinical-Pathologic Correlation in Dermatology Inpatient Consults.

Background While studies of hospital dermatology have demonstrated diagnostic discordance between primary teams and dermatology consultants, little is known about the impact of biopsy and clinical-pathologic correlation (CPC) in consultation. This study compares biopsy performance based on diagnostic discordance and evaluates the impact of CPC on the diagnosis. Methods This was a retrospective review of 376 dermatologic consultations at a single academic medical center between July 1, 2017, and June 27, 2018. Results Biopsy was significantly less likely to be performed when the diagnosis by the referring primary team was unspecified (p < 0.001). In 24 percent of cases, the diagnosis based on histopathology alone differed from the diagnosis reached by formal CPC consensus review with either potential or significant impact on management. Conclusion Dermatologists who perform inpatient consultations and rely on hospital-based pathology services may consider a consensus review for CPC. Requests to perform a biopsy may be interpreted as a request for diagnostic assistance rather than pressure to perform a procedure.

Oxytocin administration versus emotion training in healthy males: considerations for future research.

Identifying emotions correctly is essential for successful social interaction. There is therefore a keen interest in designing therapeutic interventions to improve emotion recognition in individuals who struggle with social interaction. The neuropeptide oxytocin has been proposed as a potential physiological intervention due to its important role in emotion recognition and other aspects of social cognition. However, there are a number of caveats to consider with the current form of intranasal oxytocin commonly used in the literature. Psychological interventions, on the other hand, do not carry the same caveats, and there is, therefore, a need to understand how intranasal oxytocin administration compares to psychological interventions designed to target the same psychological phenomena; and whether a combined intervention approach may provide additive benefits. Here we present a pilot, proof-of-concept study in healthy volunteers comparing the effect of intranasal oxytocin against a validated emotion training programme, finding that the psychological intervention, and not intranasal oxytocin, improved emotion recognition specifically for angry expressions. We discuss the theoretical implications of the research for future clinical trials. This article is part of the theme issue 'Interplays between oxytocin and other neuromodulators in shaping complex social behaviours'.

Physical activity and sitting time changes in response to the COVID-19 lockdown in England.

To reduce the spread of the novel coronavirus disease 2019 (COVID-19), national governments implemented measures to limit contact between citizens. This study evaluated changes in physical activity and sitting in response to the first COVID-19 lockdown in England and factors associated with these changes. A cross-sectional online survey-based study collected data from 818 adults between 29 April and 13 May 2020. Participants self-reported demographic information, physical activity and sitting for a 'typical' week before and during lockdown. Participants were grouped into low, moderate and high physical activity, and low and high (≥8 hours/day) sitting. Paired samples t-tests compared physical activity (MET-min/week) before and during lockdown. Pearson's Chi-squared evaluated the proportion of participants in the physical activity and sitting categories. Logistic regression explored associations of demographic and behavioural factors with physical activity and sitting during lockdown. Walking and total physical activity significantly increased during lockdown by 241 (95% confidence interval [CI]: 176, 304) MET-min/week and 302 (CI: 155, 457) MET-min/week, respectively (P < 0.001). There was a 4% decrease in participants engaging in low physical activity and a 4% increase in those engaging in high physical activity from before to during lockdown (P < 0.001). The proportion engaging in high sitting increased from 29% to 41% during lockdown (P < 0.001). Lower education level (odds ratio [OR] = 1.65, P = 0.045) and higher BMI (OR = 1.05, P = 0.020) were associated with increased odds of low physical activity during lockdown, whereas non-White ethnicity (OR = 0.24, P = 0.001) was associated with reduced odds. Younger age was associated with increased odds of high sitting (OR = 2.28, P = 0.008). These findings suggest that physical activity and sitting both increased during lockdown. Demographic and behavioural factors associated with low physical activity and high sitting have been identified that could inform intervention strategies during situations of home confinement.

Sex differences in psychiatric comorbidity and clinical presentation in youths with conduct disorder.

BACKGROUND: Conduct disorder (CD) rarely occurs alone but is typically accompanied by comorbid psychiatric disorders, which complicates the clinical presentation and treatment of affected youths. The aim of this study was to investigate sex differences in comorbidity pattern in CD and to systematically explore the 'gender paradox' and 'delayed-onset pathway' hypotheses of female CD. METHODS: As part of the FemNAT-CD multisite study, semistructured clinical interviews and rating scales were used to perform a comprehensive phenotypic characterization of 454 girls and 295 boys with CD (9-18 years), compared to 864 sex- and age-matched typically developing controls. RESULTS: Girls with CD exhibited higher rates of current major depression, anxiety disorders, post-traumatic stress disorder and borderline personality disorder, whereas boys with CD had higher rates of current attention-deficit/hyperactivity disorder. In line with the 'gender paradox' hypothesis, relative to boys, girls with CD showed significantly more lifetime psychiatric comorbidities (incl. Alcohol Use Disorder), which were accompanied by more severe CD symptoms. Female and male youths with CD also differed significantly in their CD symptom profiles and distribution of age-of-onset subtypes of CD (i.e. fewer girls with childhood-onset CD). In line with the 'delayed-onset pathway' hypothesis, girls with adolescent-onset CD showed similar levels of dimensional psychopathology like boys with childhood-onset CD, while boys with adolescent-onset CD had the lowest levels of internalizing psychopathology. CONCLUSIONS: Within the largest study of CD in girls performed to date, we found compelling evidence for sex differences in comorbidity patterns and clinical presentation of CD. Our findings further support aspects of the 'gender paradox' and 'delayed-onset pathway' hypotheses by showing that girls with CD had higher rates of comorbid lifetime mental disorders and functional impairments, and they usually developed CD during adolescence. These novel data on sex-specific clinical profiles of CD will be critical in informing intervention and prevention programmes.

Can facial emotion recognition be rapidly improved in children with disruptive behavior? A targeted and preventative early intervention study.

An impairment in recognizing distress is implicated in the development and severity of antisocial behavior. It has been hypothesized that a lack of attention to the eyes plays a role, but supporting evidence is limited. We developed a computerized training to improve emotion recognition in children and examined the role of eye gaze before and after training. Children referred into an intervention program to prevent antisocial outcomes completed an emotion recognition task with concurrent eye tracking. Those with emotion recognition impairments (n = 54, mean age: 8.72 years, 78% male) completed the training, while others (n = 38, mean age: 8.95 years, 84% male) continued with their usual interventions. Emotion recognition and eye gaze were reassessed in all children 8 weeks later. Impaired negative emotion recognition was significantly related to severity of behavioral problems at pretest. Children who completed the training significantly improved in emotion recognition; eye gaze did not contribute to impairment or improvement in emotion recognition. This study confirms the role of emotion recognition in severity of disruptive behavior and shows that a targeted intervention can quickly improve emotion impairments. The training works by improving children's ability to appraise emotional stimuli rather than by influencing their visual attention.

Changes to Physical Activity, Sitting Time, Eating Behaviours and Barriers to Exercise during the First COVID-19 'Lockdown' in an English Cohort.

This study aimed to determine the effect of the first English national COVID-19 lockdown on physical activity (PA), sitting time, eating behaviours and body mass in an adult cohort. This was further examined to determine whether conforming to recommended guidelines on PA and sedentary behaviour was improved. Based on an online survey (n = 818) incorporating the International Physical Activity Questionnaire Short Form (IPAQ-SF), self-reported body mass change showed that in 32.2% of participants body mass increased, with 39.1% reporting an increase in food intake. Never exercising at the gym or undertaking an exercise class (online or live), increased by 50.8% during lockdown, with 53.5% changing from exercising frequently to never exercising, suggesting a lack of engagement with online and home workouts. However, outdoor running and cycling >2 times/week increased by 38% during lockdown. Walking at least 30 min continuously on >2 occasions/week increased by 70% during lockdown with minimum 10-min walks on 7 days per week increasing by 23%. The lockdown had a negative impact on sitting time (>8 h a day), which increased by 43.6% on weekdays and 121% at weekends. Furthermore, sitting <4 h/day decreased during lockdown (46.5% and 25.6% for weekdays and weekends, respectively). Those citing tiredness or lack of time as a barrier to exercise reduced by 16% and 60%, respectively, from pre-lockdown to during lockdown. More of the sedentary group met the Public Health England PA recommendations, however most participants still did not meet the UK Government guidelines for PA. Improvements in health per additional minutes of physical activity will be proportionately greater in those previously doing <30 min/week, the area where most improvements were found although, conversely sitting time was greatly increased. This study may assist in informing whether future lifestyle changes could improve the health of the population.

Reactive angioendotheliomatosis associated with antiphospholipid syndrome.

Reactive angioendotheliomatosis (RAE) is an uncommon, benign, antiproliferative condition associated with systemic diseases that may cause occlusion or inflammation of the vascular lumina. A link between antiphospholipid syndrome (APS) and RAE has been reported a few times in the literature. Herein, we present a unique case of RAE diagnosed in a patient with primary APS who was well-managed on warfarin and rituximab with no recent thrombotic events. As RAE can precede or follow a diagnosis of APS, the presence of the condition indicates a need to workup for APS and to ensure those with the condition are adequately anticoagulated. However, as demonstrated in this case, the condition can still occur in patients who are adequately anticoagulated.

Sex-specific associations of basal steroid hormones and neuropeptides with Conduct Disorder and neuroendocrine mediation of environmental risk.

Conduct Disorder (CD) is characterized by severe aggressive and antisocial behavior. The stress hormone system has frequently been investigated as a neurobiological correlate of CD, while other interacting neuroendocrine biomarkers of sex hormone or neuropeptide systems have rarely been studied, especially in females. We examined multiple basal neuroendocrine biomarkers in female and male adolescents with CD compared to healthy controls (HCs), and explored whether they mediate effects of environmental risk factors on CD. Within the FemNAT-CD study, salivary cortisol, alpha-amylase, testosterone, dehydroepiandrosterone-sulfate (DHEA-S), estradiol, progesterone, oxytocin, and arginine-vasopressin were measured under basal conditions in 166 pubertal adolescents with CD, and 194 sex-, age-, and puberty-matched HCs (60% females, 9-18 years). Further, environmental risk factors were assessed. Single hormone analyses showed higher DHEA-S, and lower estradiol and progesterone levels in both females and males with CD relative to HCs. When accounting for interactions between neuroendocrine systems, a male-specific sex hormone factor (testosterone/DHEA-S) predicted male CD, while estradiol and a stress-system factor (cortisol/alpha-amylase) interacting with oxytocin predicted female CD. Estradiol, progesterone, and oxytocin partly explained associations between early environmental risk and CD. Findings provide evidence for sex-specific associations between basal neuroendocrine measures and CD. Especially altered sex hormones (androgen increases in males, estrogen reductions in females) robustly related to CD, while basal stress-system measures did not. Early environmental risk factors for CD may act partly through their effects on the neuroendocrine system, especially in females. Limitations (e.g., basal neuroendocrine assessment, different sample sizes per sex, pubertal participants, exploratory mediation analyses) are discussed.

Artificial intelligence in dermatopathology: Diagnosis, education, and research.

Artificial intelligence (AI) utilizes computer algorithms to carry out tasks with human-like intelligence. Convolutional neural networks, a type of deep learning AI, can classify basal cell carcinoma, seborrheic keratosis, and conventional nevi, highlighting the potential for deep learning algorithms to improve diagnostic workflow in dermatopathology of highly routine diagnoses. Additionally, convolutional neural networks can support the diagnosis of melanoma and may help predict disease outcomes. Capabilities of machine learning in dermatopathology can extend beyond clinical diagnosis to education and research. Intelligent tutoring systems can teach visual diagnoses in inflammatory dermatoses, with measurable cognitive effects on learners. Natural language interfaces can instruct dermatopathology trainees to produce diagnostic reports that capture relevant detail for diagnosis in compliance with guidelines. Furthermore, deep learning can power computation- and population-based research. However, there are many limitations of deep learning that need to be addressed before broad incorporation into clinical practice. The current potential of AI in dermatopathology is to supplement diagnosis, and dermatopathologist guidance is essential for the development of useful deep learning algorithms. Herein, the recent progress of AI in dermatopathology is reviewed with emphasis on how deep learning can influence diagnosis, education, and research.

Erythema ab igne with features resembling keratosis lichenoides chronica.

Erythema ab igne (EAI) is an asymptomatic dermatosis that develops in response to chronic exposure to low-grade heat. Characteristic findings on histopathology include epidermal atrophy, dermal elastosis, atypical histiocytes, and melanin and hemosiderin deposition. Reactive endothelial changes and prominent vascular proliferation are variable. Keratosis lichenoides chronica (KLC) is a rare lichenoid hyperkeratotic dermatosis. Acanthosis with parakeratosis and a lichenoid interface dermatitis with lymphocytes, histiocytes, and plasma cells are characteristic findings of KLC. Although its etiology remains unclear, KLC has been reported to occur in response to heat. Herein, we report a case of EAI with features resembling KLC.

Improving emotion recognition is associated with subsequent mental health and well-being in children with severe behavioural problems.

Impaired emotion recognition is a transdiagnostic risk factor for a range of psychiatric disorders. It has been argued that improving emotion recognition may lead to improvements in behaviour and mental health, but supportive evidence is limited. We assessed emotion recognition and mental health following a brief and targeted computerised emotion recognition training in children referred into an intervention program because of severe family adversity and behavioural problems (n = 62; aged 7-10). While all children continued to receive their usual interventions, only children impaired in emotion recognition (n = 40) received the emotion training. Teachers blind to whether or not children had received the training rated children's mental health problems before and 6 months after the training. Participants who received the emotion training significantly improved their recognition of negative and neutral facial expressions. Although both groups showed improved behaviour at follow-up, the reduction in behavioural problems was only significant in children who received the emotion training. Post-training emotion recognition scores predicted mental health problems 6 months later independently of initial emotion recognition ability and severity of behavioural problems. The results are consistent with the view that targeting emotion recognition can improve longer term functioning in individuals with disruptive behaviour, although further research using fully randomised designs is needed before causal conclusions can be drawn with confidence.

Intralesional immunotherapy for molluscum contagiosum: A review.

Molluscum contagiosum (MC) is a common cutaneous viral infection with no standard treatment. The virus responsible for MC is thought to be cleared by cell mediated immunity (CMI). Intralesional immunotherapy that stimulates CMI has been shown to be an effective treatment for other cutaneous viruses. In this review, we evaluate the efficacy and safety of intralesional immunotherapy in the treatment of MC. Articles met inclusion criteria if they examined the effects of intralesional immunotherapy as a treatment for MC, with a clear outcome and reproducible methodology. 228 studies were screened and 10 studies met criteria for inclusion. Intralesional immunotherapies investigated included candida, combined measles, mumps, rubella vaccine, tuberculin purified protein derivative, vitamin D3, interferon α, and Streptococcal substrain OK-432. Studies demonstrated clearance of MC lesions following intralesional immunotherapy, with complete response rates between 36% and 100%. No serious adverse effects were noted. Intralesional immunotherapy is a safe and effective treatment option for MC in pediatric and adult patients.

Neuropsychological Subgroups of Emotion Processing in Youths With Conduct Disorder.

Background: At the group level, youths with conduct disorder (CD) show deficient emotion processing across various tasks compared to typically developing controls (TDC). But little is known about neuropsychological subgroups within the CD population, the clinical correlates of emotion processing deficits [for instance, with regard to the presence or absence of the DSM-5 Limited Prosocial Emotions (LPE) specifier], and associated risk factors. Methods: 542 children and adolescents with CD (317 girls) and 710 TDCs (479 girls), aged 9-18 years, were included from the FemNAT-CD multisite study. All participants completed three neuropsychological tasks assessing emotion recognition, emotion learning, and emotion regulation. We used a self-report measure of callous-unemotional traits to create a proxy for the LPE specifier. Results: Relative to TDCs, youths with CD as a group performed worse in all three emotion domains. But using clinically based cut-off scores, we found poor emotion recognition skills in only 23% of the participants with CD, followed by emotion regulation deficits in 18%, and emotion learning deficits in 13% of the CD group. Critically, the majority of youths with CD (~56%) did not demonstrate any meaningful neuropsychological deficit, and only a very small proportion showed pervasive deficits across all three domains (~1%). Further analyses indicate that established DSM-5 subtypes of CD are not tightly linked to neurocognitive deficits in one particular emotion domain over another (i.e., emotion recognition deficits in CD+LPE vs. emotion regulation deficits in CD-LPE). Conclusions: Findings from this large-scale data set suggest substantial neuropsychological diversity in emotion processing in the CD population and, consequently, only a subgroup of youths with CD are likely to benefit from additional behavioral interventions specifically targeting emotion processing mechanisms.