An Incidental Finding of Pulmonary Cement Embolism Four Weeks After Vertebroplasty in a 50-Year-Old Man with Multiple Myeloma.

BACKGROUND Vertebroplasty is a minimally invasive radiological procedure that involves injection of cement to stabilize the fractured vertebra. It has also been increasingly used to relieve pain in patients with bone-incorporated malignancies. The most frequently encountered complication of this procedure is inadvertent cement leakage, which has the potential to embolize. This report presents an incidental finding of cement embolism during fluoroscopy for a peripherally inserted central catheter (PICC) line 4 weeks after vertebroplasty in a 50-year-old man with multiple myeloma. CASE REPORT Our report details the case of a 50-year-old man who presented for progressive sciatic nerve pain and was found on imaging to have an L3 fracture, spinal stenosis, lumbar spinal spondylosis, and diffusely decreased bone density, eventually diagnosed with multiple myeloma. For symptomatic relief and vertebrae stabilization, he underwent a CT-guided fluoroscopic vertebroplasty procedure. Four weeks later, during fluoroscopy for a PICC, he was incidentally found to have radiopaque opacities within the pulmonary arteries. He was diagnosed with a pulmonary embolism due to transvertebral cement leakage from his vertebroplasty. Given the central nature of his embolism, he was treated with anticoagulation and closely monitored. Throughout the treatment period, he remained asymptomatic with normal vital signs and NT-brain natriuretic peptide. CONCLUSIONS This report highlights the association between vertebroplasty and pulmonary cement embolism (PCE), the potential for late detection upon chest imaging even weeks after vertebroplasty, and suggests that some patients with PCE may need therapeutic anticoagulation.

Deep phenotypic analysis of psychiatric features in genetically defined cohorts: application to XYY syndrome.

BACKGROUND: Recurrent gene dosage disorders impart substantial risk for psychopathology. Yet, understanding that risk is hampered by complex presentations that challenge classical diagnostic systems. Here, we present a suite of generalizable analytic approaches for parsing this clinical complexity, which we illustrate through application to XYY syndrome. METHOD: We gathered high-dimensional measures of psychopathology in 64 XYY individuals and 60 XY controls, plus additional interviewer-based diagnostic data in the XYY group. We provide the first comprehensive diagnostic description of psychiatric morbidity in XYY syndrome and show how diagnostic morbidity relates to functioning, subthreshold symptoms, and ascertainment bias. We then map behavioral vulnerabilities and resilience across 67 behavioral dimensions before borrowing techniques from network science to resolve the mesoscale architecture of these dimensions and links to observable functional outcomes. RESULTS: Carriage of an extra Y-chromosome increases risk for diverse psychiatric diagnoses, with clinically impactful subthreshold symptomatology. Highest rates are seen for neurodevelopmental and affective disorders. A lower bound of < 25% of carriers are free of any diagnosis. Dimensional analysis of 67 scales details the profile of psychopathology in XYY, which survives control for ascertainment bias, specifies attentional and social domains as the most impacted, and refutes stigmatizing historical associations between XYY and violence. Network modeling compresses all measured symptom scales into 8 modules with dissociable links to cognitive ability, adaptive function, and caregiver strain. Hub modules offer efficient proxies for the full symptom network. CONCLUSIONS: This study parses the complex behavioral phenotype of XYY syndrome by applying new and generalizable analytic approaches for analysis of deep-phenotypic psychiatric data in neurogenetic disorders.

Comparison of Anxiety and Depression Symptoms in Concussed and Nonconcussed Adolescents.

BACKGROUND: Few studies have examined psychiatric symptoms during the acute phase following a concussion in adolescents. Thus, this study compares anxiety and depression in acutely concussed and nonconcussed adolescents. HYPOTHESIS: Acutely concussed adolescents will report greater anxiety and depressive symptoms compared with nonconcussed adolescents. STUDY DESIGN: Prospective cohort study. LEVEL OF EVIDENCE: Level 3. METHODS: Data were collected from 282 adolescents (111 concussed within 28 days of injury, 171 nonconcussed), 13 to 18 years of age, who completed Patient-Reported Outcome Measurement Information System (PROMIS) Anxiety and Depressive Symptoms measures. We calculated average T-scores for anxiety and depression across both groups and compared the proportion of those who scored above normal limits. Finally, we calculated risk ratios for anxiety and depression scores above normal limits. RESULTS: Average T-scores for anxiety did not differ in concussed versus nonconcussed adolescents (mean: 45.9 [SD 10.84] vs 45.2 [8.1], respectively, P = 0.54), whereas average T-scores for depression were significantly higher in concussed versus nonconcussed adolescents (46.0 [10.88] vs 42.8 [8.48], respectively, P < 0.01). The proportion of concussed adolescents above normal limits for depression was greater than nonconcussed adolescents (32.4% vs 20.5%, respectively, P = 0.02). Post hoc sensitivity analyses excluding those with a history of anxiety or depression demonstrated a 1.45 (95% CI, 0.97, 2.01) and 1.56 (95% CI, 0.95, 2.56) increased risk of an above-normal anxiety and depression score for concussed compared with nonconcussed adolescents, respectively, although both were nonsignificant. CONCLUSION: Although we found few significant differences between the 2 groups, the results highlight that many concussed adolescents met the threshold for above-average symptoms on the depression and anxiety PROMIS measures. CLINICAL RELEVANCE: In adolescents, there is increased risk for psychiatric sequalae in the acute period after a concussion. As such, we suggest that clinicians consider incorporating depression screening when caring for adolescents after a concussion.

Curriculum Development by Design Thinking: Analyzing a Program for Social Determinants of Health Screening by Pre-Clerkship Medical Students.

PROBLEM: Health systems science (HSS) curricula in medical schools facilitate an understanding of social determinants of health (SDOH) and their impact on health outcomes. After implementation of an experiential, patient-centered program based around SDOH screening, however, our medical college noted poor student receptivity and engagement. In order to improve the program, we chose a design thinking approach based on the perceived value of actively engaging learners in the design of education. The role of design thinking in curricular quality improvement, however, remains unclear. INTERVENTION: We sought to determine if a current educational model for SDOH screening could be improved by reforming the curriculum using a design thinking workshop involving student and faculty stakeholders. CONTEXT: The current study is a retrospective analysis of first-year medical student, end-of-year evaluations of the Clinical Experience (CE) program at the Sidney Kimmel Medical College before (2018-19) and after (2019-20) implementation of the design thinking workshop and subsequent curriculum changes. IMPACT: Overall positive results significantly increased across all survey questions after the curricular intervention (p < 0.01), indicating increased student satisfaction with the revised curriculum. LESSONS LEARNED: Few studies assess outcomes of design thinking-driven curricular changes. The current study of an SDOH screening program details the implementation of initiatives that originated from a design thinking sprint and assesses program evaluations following these curricular changes. Most of the well-received curricular changes concerned improvements in student training, patient screening and follow-up, and the leveraging of existing technology. The study reinforces the importance of co-creation among stakeholders when redesigning medical curricula.

Virtual Community Health Workers: Approaches to Patient Outreach During the COVID-19 Pandemic.

BACKGROUND: Prior to the COVID-19 pandemic, community health workers (CHWs) in our health system screened patients in-person for social determinants of health and connected them to community resources. However, when our CHWs were required to work remotely from home due to the pandemic, the best platform to optimize contacting these patients was unknown. This study sought to evaluate the effectiveness of three outgoing phone call approaches (*67, Google Voice®, and Doximity Dialer®) in successfully contacting patients. METHODS: We performed a retrospective analysis comparing reach rates across the three outgoing call approaches. RESULTS: Reach rates were highest when Doximity Dialer was used (64.0%, 95% CI: 58.8-69.0) compared with *67 (40.8%, 95% CI: 30.8-51.6) or Google Voice (53.2%, 95% CI: 48.4-57.8) in this analysis of 1,144 outreach calls. CONCLUSION: Due to higher reach rates, we recommend Doximity Dialer for phone-based outreach to patients. Additional research to improve the efficacy of remote outreach is warranted.

Modeling familial predictors of proband outcomes in neurogenetic disorders: initial application in XYY syndrome.

BACKGROUND: Disorders of gene dosage can significantly increase risk for psychopathology, but outcomes vary greatly amongst carriers of any given chromosomal aneuploidy or sub-chromosomal copy number variation (CNV). One potential path to advance precision medicine for neurogenetic disorders is modeling penetrance in probands relative to observed phenotypes in their non-carrier relatives. Here, we seek to advance this general analytic framework by developing new methods in application to XYY syndrome-a sex chromosome aneuploidy that is known to increase risk for psychopathology. METHODS: We analyzed a range of cognitive and behavioral domains in XYY probands and their non-carrier family members (n = 58 families), including general cognitive ability (FSIQ), as well as continuous measures of traits related to autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Proband and relative scores were compared using covariance, regression and cluster analysis. Comparisons were made both within and across traits. RESULTS: Proband scores were shifted away from family scores with effect sizes varying between 0.9 and 2.4 across traits. Only FSIQ and vocabulary scores showed a significant positive correlation between probands and their non-carrier relatives across families (R2 ~ 0.4). Variability in family FSIQ also cross-predicted variability in proband ASD trait severity. Cluster analysis across all trait-relative pairings revealed that variability in parental psychopathology was more weakly coupled to their XYY versus their euploid offspring. CONCLUSIONS: We present a suite of generalizable methods for modeling variable penetrance in aneuploidy and CNV carriers using family data. These methods update estimates of phenotypic penetrance for XYY and suggest that the predictive utility of family data is likely to vary for different traits and different gene dosage disorders. TRIAL REGISTRATIONS: ClinicalTrials.gov NCT00001246 , "89-M-0006: Brain Imaging of Childhood Onset Psychiatric Disorders, Endocrine Disorders and Healthy Controls." Date of registry: 01 October 1989.

Sex-biased trajectories of amygdalo-hippocampal morphology change over human development.

The amygdala and hippocampus are two adjacent allocortical structures implicated in sex-biased and developmentally-emergent psychopathology. However, the spatiotemporal dynamics of amygdalo-hippocampal development remain poorly understood in healthy humans. The current study defined trajectories of volume and shape change for the amygdala and hippocampus by applying a multi-atlas segmentation pipeline (MAGeT-Brain) and semi-parametric mixed-effects spline modeling to 1,529 longitudinally-acquired structural MRI brain scans from a large, single-center cohort of 792 youth (403 males, 389 females) between the ages of 5 and 25 years old. We found that amygdala and hippocampus volumes both follow curvilinear and sexually dimorphic growth trajectories. These sex-biases were particularly striking in the amygdala: males showed a significantly later and slower adolescent deceleration in volume expansion (at age 20 years) than females (age 13 years). Shape analysis localized significant hot-spots of sex-biased anatomical development in sub-regional territories overlying rostral and caudal extremes of the CA1/2 in the hippocampus, and the centromedial nuclear group of the amygdala. In both sexes, principal components analysis revealed close integration of amygdala and hippocampus shape change along two main topographically-organized axes - low vs. high areal expansion, and early vs. late growth deceleration. These results (i) bring greater resolution to our spatiotemporal understanding of amygdalo-hippocampal development in healthy males and females, and (ii) uncover focal sex-differences in the structural maturation of the brain components that may contribute to differences in behavior and psychopathology that emerge during adolescence.

Allometric Analysis Detects Brain Size-Independent Effects of Sex and Sex Chromosome Complement on Human Cerebellar Organization.

The cerebellum is a large hindbrain structure that is increasingly recognized for its contribution to diverse domains of cognitive and affective processing in human health and disease. Although several of these domains are sex biased, our fundamental understanding of cerebellar sex differences-including their spatial distribution, potential biological determinants, and independence from brain volume variation-lags far behind that for the cerebrum. Here, we harness automated neuroimaging methods for cerebellar morphometrics in 417 individuals to (1) localize normative male-female differences in raw cerebellar volume, (2) compare these to sex chromosome effects estimated across five rare sex (X/Y) chromosome aneuploidy (SCA) syndromes, and (3) clarify brain size-independent effects of sex and SCA on cerebellar anatomy using a generalizable allometric approach that considers scaling relationships between regional cerebellar volume and brain volume in health. The integration of these approaches shows that (1) sex and SCA effects on raw cerebellar volume are large and distributed, but regionally heterogeneous, (2) human cerebellar volume scales with brain volume in a highly nonlinear and regionally heterogeneous fashion that departs from documented patterns of cerebellar scaling in phylogeny, and (3) cerebellar organization is modified in a brain size-independent manner by sex (relative expansion of total cerebellum, flocculus, and Crus II-lobule VIIIB volumes in males) and SCA (contraction of total cerebellar, lobule IV, and Crus I volumes with additional X- or Y-chromosomes; X-specific contraction of Crus II-lobule VIIIB). Our methods and results clarify the shifts in human cerebellar organization that accompany interwoven variations in sex, sex chromosome complement, and brain size.SIGNIFICANCE STATEMENT Cerebellar systems are implicated in diverse domains of sex-biased behavior and pathology, but we lack a basic understanding of how sex differences in the human cerebellum are distributed and determined. We leverage a rare neuroimaging dataset to deconvolve the interwoven effects of sex, sex chromosome complement, and brain size on human cerebellar organization. We reveal topographically variegated scaling relationships between regional cerebellar volume and brain size in humans, which (1) are distinct from those observed in phylogeny, (2) invalidate a traditional neuroimaging method for brain volume correction, and (3) allow more valid and accurate resolution of which cerebellar subcomponents are sensitive to sex and sex chromosome complement. These findings advance understanding of cerebellar organization in health and sex chromosome aneuploidy.

Influences of Brain Size, Sex, and Sex Chromosome Complement on the Architecture of Human Cortical Folding.

Gyrification is a fundamental property of the human cortex that is increasingly studied by basic and clinical neuroscience. However, it remains unclear if and how the global architecture of cortical folding varies with 3 interwoven sources of anatomical variation: brain size, sex, and sex chromosome dosage (SCD). Here, for 375 individuals spanning 7 karyotype groups (XX, XY, XXX, XYY, XXY, XXYY, XXXXY), we use structural neuroimaging to measure a global sulcation index (SI, total sulcal/cortical hull area) and both determinants of sulcal area: total sulcal length and mean sulcal depth. We detail large and patterned effects of sex and SCD across all folding metrics, but show that these effects are in fact largely consistent with the normative scaling of cortical folding in health: larger human brains have disproportionately high SI due to a relative expansion of sulcal area versus hull area, which arises because disproportionate sulcal lengthening overcomes a lack of proportionate sulcal deepening. Accounting for these normative allometries reveals 1) brain size-independent sulcal lengthening in males versus females, and 2) insensitivity of overall folding architecture to SCD. Our methodology and findings provide a novel context for future studies of human cortical folding in health and disease.

Callous-Unemotional Traits Trajectories Interact with Earlier Conduct Problems and Executive Control to Predict Violence and Substance Use Among High Risk Male Adolescents.

Callous-unemotional (CU) traits, conduct problems (CP), and deficits in executive control are all linked to the development of more severe antisocial behavior, including violence and substance use. Though previous research has examined the impact of these factors on antisocial outcomes, little work has examined trajectories of CU traits across adolescence and how these trajectories predict greater antisocial behavior in adulthood. Moreover, no study has assessed how severity of early CP and executive control may exacerbate these pathways and increase risk for later violence and substance use. The current study (a) identified trajectories of CU traits among a large, high-risk sample of adolescent males, (b) examined the relationship between CU traits trajectories and future violence and substance use, and (c) examined whether early CP and executive control moderated the effects of a high CU traits trajectory membership and high CP on violence and substance use. Results indicated that: (a) CU traits could be grouped into three stable trajectories across adolescence, (b) the 'high' CU traits trajectory, particularly in the presence of 'elevated' CP, was related to higher violence and substance use, over and above a variety of environmental risk factors, and (c) the effects the 'high' CU traits trajectory on both violence and substance and in the presence of 'elevated' CP was stronger among youth with high executive control. These findings highlight the utility of identifying subgroups of youth who differ on trajectories of CU traits for understanding the development and maintenance of severe antisocial behavior.