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PURPOSE/OBJECTIVES: To review the history of thalidomide, examine fears emanating from its renewed usage, and discuss the nurse's critical role in patient education. DATA SOURCES: Published articles, abstracts, books, and clinical experience. DATA SYNTHESIS: In the early 1960s, the teratogenic effects of thalidomide became widely known. The words thalidomide and birth defects became permanently linked as a result of pregnant women who used thalidomide as a sedative, thus giving birth to children with horrific birth defects. As researchers look at novel properties of drugs and new indications in the oncologic setting, thalidomide has made a comeback, particularly in the treatment of multiple myeloma. Patient education is important to combat fear in using and prescribing thalidomide and is essential in preventing birth defects and other side effects associated with thalidomide use. CONCLUSIONS: Nurses are vital in the patient-education process, yet on extensive nursing literature search revealed limited publications regarding thalidomide. Nurses can prevent thalidomide-associated birth defects through comprehensive patient education and can assist patients in decreasing any anxiety related to potential and actual side effects. IMPLICATIONS FOR NURSING PRACTICE: With careful patient monitoring and comprehensive education of physicians, nurses, and patients, it is possible to reap the benefits of thalidomide and avoid the tragedy of misues. Nurses are in the forefront of education, and their expertise will empower patients to use thalidomide responsibly. [ABSTRACT FROM AUTHOR]

Abstract Background As a model organism in biomedicine, the rhesus macaque (Macaca mulatta) is the most widely used nonhuman primate. Although a draft genome sequence was completed in 2007, there has been no systematic genome-wide comparison of genetic variation of this species to humans. Comparative analysis of functional and nonfunctional diversity in this highly abundant and adaptable non-human primate could inform its use as a model for human biology, and could reveal how variation in population history and size alters patterns and levels of sequence variation in primates. Results We sequenced the mRNA transcriptome and H3K4me3-marked DNA regions in hippocampus from 14 humans and 14 rhesus macaques. Using equivalent methodology and sampling spaces, we identified 462,802 macaque SNPs, most of which were novel and disproportionately located in the functionally important genomic regions we had targeted in the sequencing. At least one SNP was identified in each of 16,797 annotated macaque genes. Accuracy of macaque SNP identification was conservatively estimated to be >90%. Comparative analyses using SNPs equivalently identified in the two species revealed that rhesus macaque has approximately three times higher SNP density and average nucleotide diversity as compared to the human. Based on this level of diversity, the effective population size of the rhesus macaque is approximately 80,000 which contrasts with an effective population size of less than 10,000 for humans. Across five categories of genomic regions, intergenic regions had the highest SNP density and average nucleotide diversity and CDS (coding sequences) the lowest, in both humans and macaques. Although there are more coding SNPs (cSNPs) per individual in macaques than in humans, the ratio of dN/dS is significantly lower in the macaque. Furthermore, the number of damaging nonsynonymous cSNPs (have damaging effects on protein functions from PolyPhen-2 prediction) in the macaque is more closely equivalent to that of the human. Conclusions This large panel of newly identified macaque SNPs enriched for functionally significant regions considerably expands our knowledge of genetic variation in the rhesus macaque. Comparative analysis reveals that this widespread, highly adaptable species is approximately three times as diverse as the human but more closely equivalent in damaging variation.

Abstract Background The objectives of this study were to characterize the satisfaction of Pediatric Infectious Diseases fellows with their training and to understand how opinions about training have changed over time. Methods Anonymous survey studies were conducted with questions designed to include areas related to the 6 ACGME core competencies. Surveys for current fellows were distributed by fellowship directors, while surveys for graduates were mailed to all individuals with Pediatric Infectious Diseases certification. Results Response rates for current fellows and graduates were 50% and 52%, respectively. Most fellows (98%) and graduates (92%) perceived their overall training favorably. Training in most clinical care areas was rated favorably, however both groups perceived relative deficiencies in several areas. Current fellows rated their training in other competency areas (e.g., systems-based practice, research, and ethics) more favorably when compared to past graduates. Recent graduates perceived their training more favorably in many of these areas compared to past graduates. Conclusions Pediatric Infectious Diseases fellowship training is well regarded by the majority of current and past trainees. Views of current fellows reflect improved satisfaction with training in a variety of competency areas. Persistent deficiencies in clinical training likely reflect active barriers to education. Additional study is warranted to validate perceived deficiencies and to establish consensus on the importance of these areas to infectious diseases training.

Abstract Background We have used a genetical genomic approach, in conjunction with phenotypic analysis of alcohol consumption, to identify candidate genes that predispose to varying levels of alcohol intake by HXB/BXH recombinant inbred rat strains. In addition, in two populations of humans, we assessed genetic polymorphisms associated with alcohol consumption using a custom genotyping array for 1,350 single nucleotide polymorphisms (SNPs). Our goal was to ascertain whether our approach, which relies on statistical and informatics techniques, and non-human animal models of alcohol drinking behavior, could inform interpretation of genetic association studies with human populations. Results In the HXB/BXH recombinant inbred (RI) rats, correlation analysis of brain gene expression levels with alcohol consumption in a two-bottle choice paradigm, and filtering based on behavioral and gene expression quantitative trait locus (QTL) analyses, generated a list of candidate genes. A literature-based, functional analysis of the interactions of the products of these candidate genes defined pathways linked to presynaptic GABA release, activation of dopamine neurons, and postsynaptic GABA receptor trafficking, in brain regions including the hypothalamus, ventral tegmentum and amygdala. The analysis also implicated energy metabolism and caloric intake control as potential influences on alcohol consumption by the recombinant inbred rats. In the human populations, polymorphisms in genes associated with GABA synthesis and GABA receptors, as well as genes related to dopaminergic transmission, were associated with alcohol consumption. Conclusion Our results emphasize the importance of the signaling pathways identified using the non-human animal models, rather than single gene products, in identifying factors responsible for complex traits such as alcohol consumption. The results suggest cross-species similarities in pathways that influence predisposition to consume alcohol by rats and humans. The importance of a well-defined phenotype is also illustrated. Our results also suggest that different genetic factors predispose alcohol dependence versus the phenotype of alcohol consumption.

Abstract Background We previously demonstrated that chronic pulmonary infection with Cryptococcus neoformans results in enhanced allergic inflammation and airway hyperreactivity in a rat model. Because the cell wall of C. neoformans consists of chitin, and since acidic mammalian chitinase (AMCase) has recently been implicated as a novel mediator of asthma, we sought to determine whether such infection induces chitinase activity and expression of AMCase in the rat. Methods We utilized a previously-established model of chronic C. neoformans pulmonary infection in the rat to analyze the activity, expression and localization of AMCase. Results Our studies indicate that intratracheal inoculation of C. neoformans induces chitinase activity within the lung and bronchoalveolar lavage fluid of infected rats. Chitinase activity is also elicited by pulmonary infection with other fungi (e.g. C. albicans), but not by the inoculation of dead organisms. Enhanced chitinase activity reflects increased AMCase expression by airway epithelial cells and alveolar macrophages. Systemic cryptococcosis is not associated with increased pulmonary chitinase activity or AMCase expression. Conclusion Our findings indicate a possible link between respiratory fungal infections, including C. neoformans, and asthma through the induction of AMCase.

Abstract Background Because excessive reduction in activities after back injury may impair recovery, it is important to understand and address the factors contributing to the variability in motor responses to pain. The current dominant theory is the "fear-avoidance model", in which the some patients' heightened fears of further injury cause them to avoid movement. We propose that in addition to psychological factors, neurochemical variants in the circuits controlling movement and their modification by pain may contribute to this variability. A systematic search of the motor research literature and genetic databases yielded a prioritized list of polymorphic motor control candidate genes. We demonstrate an analytic method that we applied to 14 of these genes in 290 patients with acute sciatica, whose reduction in movement was estimated by items from the Roland-Morris Disability Questionnaire. Results We genotyped a total of 121 single nucleotide polymorphisms (SNPs) in 14 of these genes, which code for the dopamine D2 receptor, GTP cyclohydrolase I, glycine receptor α1 subunit, GABA-A receptor α2 subunit, GABA-A receptor β1 subunit, α-adrenergic 1C, 2A, and 2C receptors, serotonin 1A and 2A receptors, cannabinoid CB-1 receptor, M1 muscarinic receptor, and the tyrosine hydroxylase, and tachykinin precursor-1 molecules. No SNP showed a significant association with the movement score after a Bonferroni correction for the 14 genes tested. Haplotype analysis of one of the blocks in the GABA-A receptor β1 subunit showed that a haplotype of 11% frequency was associated with less limitation of movement at a nominal significance level value (p = 0.0025) almost strong enough to correct for testing 22 haplotype blocks. Conclusion If confirmed, the current results may suggest that a common haplotype in the GABA-A β1 subunit acts like an "endogenous muscle relaxant" in an individual with subacute sciatica. Similar methods might be applied a larger set of genes in animal models and human laboratory and clinical studies to understand the causes and prevention of pain-related reduction in movement.

Abstract Background The risk of schizophrenia is thought to be higher in population isolates that have recently been exposed to major and accelerated cultural change, accompanied by ensuing socio-environmental stressors/triggers, than in dominant, mainstream societies. We investigated the prevalence and phenomenology of schizophrenia in 329 females and 253 males of a Southwestern American Indian tribe, and in 194 females and 137 males of a Plains American Indian tribe. These tribal groups were evaluated as part of a broader program of gene-environment investigations of alcoholism and other psychiatric disorders. Methods Semi-structured psychiatric interviews were conducted to allow diagnoses utilizing standardized psychiatric diagnostic criteria, and to limit cultural biases. Study participants were recruited from the community on the basis of membership in pedigrees, and not by convenience. After independent raters evaluated the interviews blindly, DSM-III-R diagnoses were assigned by a consensus of experts well-versed in the local cultures. Results Five of the 582 Southwestern American Indian respondents (prevalence = 8.6 per 1000), and one of the 331 interviewed Plains American Indians (prevalence = 3.02 per 1000) had a lifetime diagnosis of schizophrenia. The lifetime prevalence rates of schizophrenia within these two distinct American Indian tribal groups is consistent with lifetime expectancy rates reported for the general United States population and most isolate and homogeneous populations for which prevalence rates of schizophrenia are available. While we were unable to factor in the potential modifying effect that mortality rates of schizophrenia-suffering tribal members may have had on the overall tribal rates, the incidence of schizophrenia among the living was well within the normative range. Conclusion The occurrence of schizophrenia among members of these two tribal population groups is consistent with prevalence rates reported for population isolates and in the general population. Vulnerabilities to early onset alcohol and drug use disorders do not lend convincing support to a diathesis-stressor model with these stressors, commonly reported with these tribes. Nearly one-fifth of the respondents reported experiencing psychotic-like symptoms, reaffirming the need to examine sociocultural factors actively before making positive diagnoses of psychosis or schizophrenia.

Abstract Background Pain patients are often depressed and anxious, and benefit less from psychotropic drugs than pain-free patients. We hypothesize that this partial resistance is due to the unique neurochemical contribution to mood by afferent pain projections through the spino-parabrachial-hypothalamic-amygdalar systems and their projections to other mood-mediating systems. New psychotropic drugs for pain patients might target molecules in such brain systems. We propose a method to prioritize molecular targets by studying polymorphic genes in cohorts of patients undergoing surgical procedures associated with a variable pain relief response. We seek molecules that show a significant statistical interaction between (1) the amount of surgical pain relief, and (2) the alleles of the gene, on depression and anxiety during the first postoperative year. Results We collected DNA from 280 patients with sciatica due to a lumbar disc herniation, 162 treated surgically and 118 non-surgically, who had been followed for 10 years in the Maine Lumbar Spine Study, a large, prospective, observational study. In patients whose pain was reduced >25% by surgery, symptoms of depression and anxiety, assessed with the SF-36 Mental Health Scale, improved briskly at the first postoperative measurement. In patients with little or no surgical pain reduction, mood scores stayed about the same on average. There was large inter-individual variability at each level of residual pain. Polymorphisms in three pre-specified pain-mood candidate genes, catechol-O-methyl transferase (COMT), serotonin transporter, and brain-derived neurotrophic factor (BDNF) were not associated with late postoperative mood or with a pain-gene interaction on mood. Although the sample size did not provide enough power to persuasively search through a larger number of genes, an exploratory survey of 25 other genes provides illustrations of pain-gene interactions on postoperative mood – the mu opioid receptor for short-term effects of acute sciatica on mood, and the galanin-2 receptor for effects of unrelieved post-discectomy pain on mood one year after surgery. Conclusion Genomic analysis of longitudinal studies of pain, depression, and anxiety in patients undergoing pain-relieving surgery may help to identify molecules through which pain alters mood. Detection of alleles with modest-sized effects will require larger cohorts.

This study argues that value assessment conducted from a societal perspective should rely on the Generalized Cost-Effectiveness Analysis (GCEA) framework proposed herein. Recently developed value assessment inventories - such as the Second Panel on Cost-Effectiveness's "impact inventory" and International Society of Pharmacoeconomics Outcomes Research (ISPOR) "value flower" - aimed to more comprehensively capture the benefits and costs of new health technologies from a societal perspective. Nevertheless, application of broader value elements in practice has been limited in part because quantifying these elements can be complex, but also because there have been numerous methodological advances since these value inventories have been released (e.g. generalized and risk-adjusted cost effectiveness). To facilitate estimation of treatment value from a societal perspective, this paper provides an updated value inventory - called the GCEA value flower - and a user guide for implementing GCEA for health economics researchers and practitioners. GCEA considers 15 broader value elements across four categories: (i) uncertainty, (ii) dynamics, (iii) beneficiary, and (iv) additional value components. The uncertainty category incorporates patient risk preferences into value assessment. The dynamics category petals account for the evolution of real-world treatment value (e.g. option value) and includes drug pricing trends (e.g. future genericization). The beneficiary category accounts for the fact health technologies can benefit others (e.g. caregivers) and also that society may care to whom health benefits accrue (e.g. equity). Finally, GCEA incorporates additional broader sources of value (e.g. community spillovers, productivity losses). This GCEA user guide aims to facilitate both the estimation of each of these value elements and the incorporation of these values into health technology assessment when conducted from a societal perspective., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

Objective: To determine if cancer patients experience variability in incidence or management of emergency general surgery (EGS) conditions compared to non-cancer patients., Background: The true frequency, and natural history of EGS conditions among cancer patients has not been characterized., Methods: We utilized SEER-Medicare data from January 2006-December 2015 to compare patients with breast, prostate, and lung cancer to a non-cancer cohort. Patients were followed from date of cancer diagnosis, or an index date for non-cancer patients, to the development of an EGS condition, death or last follow up. We assessed the cumulative incidence of EGS conditions over time, and fit multivariable Cox proportional hazards models to evaluate the impact of time-dependent surgical intervention on mortality., Results: We identified 322,756 patients with breast (N=82,147), lung (N=128,618), and prostate cancer (N=111,991) and 210,429 non-cancer patients.. Cancer patients had a higher incidence of an EGS condition within the first year after diagnosis (4.8% vs. 3.2%), with lung (6.8%) and breast cancer (4.0%) showing consistent rends. Cancer patients were less likely to undergo surgery for (13% vs. 14%, P=0.005), though this varied by cancer type and EGS conditions. Patients with breast (HR 1.27, 95%CI 1.17-1.39) and lung cancer (HR 3.27, 95%CI 3.07-3.48) were more likely to die within 30-days of an EGS diagnosis., Conclusions: Cancer patients experience a higher incidence of EGS conditions within the first year following diagnosis, but are less likely to undergo surgery. Future research is needed to explore the interplay between EGS conditions, their management, and receipt of intended oncologic therapy, and resulting outcomes., Competing Interests: Conflicts of Interest: ACW reports consulting payment from HistoSonics and institutional clinical trial support from Ipsen. JSJ, SML, DAG, SMM, ELV, KSP have no real or apparent conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Neurodevelopmental mechanisms are increasingly implicated in bipolar disorder (BD), highlighting the importance of their study in young persons. Neuroimaging studies have demonstrated a central role for frontotemporal corticolimbic brain systems that subserve processing and regulation of emotions, and processing of reward in adults with BD. As adolescence and young adulthood (AYA) is a time when fully syndromal BD often emerges, and when these brain systems undergo dynamic maturational changes, the AYA epoch is implicated as a critical period in the neurodevelopment of BD. Functional magnetic resonance imaging (fMRI) studies can be especially informative in identifying the functional neuroanatomy in adolescents and young adults with BD (BD AYA ) and at high risk for BD (HR-BD AYA ) that is related to acute mood states and trait vulnerability to the disorder. The identification of early emerging brain differences, trait- and state-based, can contribute to the elucidation of the developmental neuropathophysiology of BD, and to the generation of treatment and prevention targets. In this critical review, fMRI studies of BD AYA and HR-BD AYA are discussed, and a preliminary neurodevelopmental model is presented based on a convergence of literature that suggests early emerging dysfunction in subcortical (e.g., amygdalar, striatal, thalamic) and caudal and ventral cortical regions, especially ventral prefrontal cortex (vPFC) and insula, and connections among them, persisting as trait-related features. More rostral and dorsal cortical alterations, and bilaterality progress later, with lateralization, and direction of functional imaging findings differing by mood state. Altered functioning of these brain regions, and regions they are strongly connected to, are implicated in the range of symptoms seen in BD, such as the insula in interoception, precentral gyrus in motor changes, and prefrontal cortex in cognition. Current limitations, and outlook on the future use of neuroimaging evidence to inform interventions and prevent the onset of mood episodes in BD AYA , are outlined., (© 2024. The Author(s).)

Background: The majority of non-metastatic breast cancer patients in sub-Saharan Africa are recommended to have mastectomy. The impact of mastectomy on a predominantly young African patient population requires evaluation. The BREAST-Q is a validated patient-reported outcome measure of quality-of-life following breast surgery that has been translated into 30 languages-none in Africa. This study aimed to translate and assess the psychometric properties of the mastectomy module of the BREAST-Q for use in Nigeria., Methods: The BREAST-Q mastectomy module was translated from English to Yoruba and its psychometric properties assessed using best practice guidelines. Translation was performed in 4 steps: forward translation (x2), back translation, back translation review, and cognitive interviews with post-mastectomy patients. The translated BREAST-Q instrument was administered to post-mastectomy patients (n = 21) alongside the EORTC-QLQ BR23 to evaluate construct validity. Test-retest reliability was evaluated using intraclass correlation coefficients (ICC); surveys were re-administered 4 weeks apart., Results: The translation process identified English phrases not amenable to direct translation, including "emotionally healthy" and descriptions of pain ("nagging," "throbbing," "sharp"). Translations were amended to reflect local context and question intent. During cognitive interviews, patients provided suggestions to simplify complex phrases, e.g. "discomfort in your breast area.". Internal consistency within scales was over 0.70 for psychosocial wellbeing (α = 0.84-0.87), sexual wellbeing (α = 0.98-0.99), physical wellbeing in chest (α = 0.84-0.86), and satisfaction with care (α = 0.89-0.93). ICC for test-retest reliability was moderate (0.46-0.63)., Conclusions: The Yoruba version of the BREAST-Q mastectomy module presents a unique opportunity to adequately capture the experiences of Nigerian women post mastectomy. This instrument is being used in a pilot study of Nigerian patients to identify targets for intervention to improve the patient experience and compliance with breast cancer surgery., (© 2024. The Author(s).)

Background: The study is aimed to identify brain functional connectomes predictive of depressed and elevated mood symptomatology in individuals with bipolar disorder (BD) using the machine learning approach Connectome-based Predictive Modeling (CPM)., Methods: Functional magnetic resonance imaging data were obtained from 81 adults with BD while they performed an emotion processing task. CPM with 5000 permutations of leave-one-out cross-validation was applied to identify functional connectomes predictive of depressed and elevated mood symptom scores on the Hamilton Depression and Young Mania rating scales. The predictive ability of the identified connectomes was tested in an independent sample of 43 adults with BD., Results: CPM predicted the severity of depressed [concordance between actual and predicted values ( r = 0.23, p perm (permutation test) = 0.031) and elevated ( r = 0.27, p perm = 0.01) mood. Functional connectivity of left dorsolateral prefrontal cortex and supplementary motor area nodes, with inter- and intra-hemispheric connections to other anterior and posterior cortical, limbic, motor, and cerebellar regions, predicted depressed mood severity. Connectivity of left fusiform and right visual association area nodes with inter- and intra-hemispheric connections to the motor, insular, limbic, and posterior cortices predicted elevated mood severity. These networks were predictive of mood symptomatology in the independent sample ( r ⩾ 0.45, p = 0.002)., Conclusions: This study identified distributed functional connectomes predictive of depressed and elevated mood severity in BD. Connectomes subserving emotional, cognitive, and psychomotor control predicted depressed mood severity, while those subserving emotional and social perceptual functions predicted elevated mood severity. Identification of these connectome networks may help inform the development of targeted treatments for mood symptoms.

Background: Older adults with bipolar disorder (BD) have received little study, although they often have severe symptoms, treatment resistance and high suicide risk. Furthermore, a subset develops cognitive dysfunction for unknown reasons., Methods: Here, cortical thickness and subcortical gray matter volume were compared across individuals ages 40-79y: 103 with BD ("later-onset" at ages ≥25y, n = 21; "early-onset" < 25y, n = 82) and healthy controls (HCs, n = 98)., Results: Overall, those with BD showed lower prefrontal, cingulate, sensorimotor, parahippocampal, insula, temporal, parietal, and occipital cortical thickness (Cohen's d: 0.4 to 0.8) and hippocampal, amygdalar, thalamic, and striatal gray matter volume (d: 0.6 to 0.8). Later-onset BD showed negative relationships between age and parahippocampal, insular, temporal, parietal, and occipital cortical thickness, and hippocampal, thalamic and striatal volume (r: -0.7 to -0.4). Suicide attempt history was associated with lower dorsolateral prefrontal cortical thickness (d = 0.5)., Limitations: The study used a cross-sectional design and the sample of those with a later-onset of BD was relatively modest., Conclusions: Results support widespread gray matter decreases in older adults with BD, and also suggest a separable later-onset phenotype characterized by age-related gray matter reductions in regions subserving cognitive, emotional and perceptual processes. Moreover, the results are the first to demonstrate structural brain differences associated with a history of suicide attempts in older adults with BD., Competing Interests: Conflict of Interest GSA serves on the advisory board of Eisai, and of Janssen, and serves on the Speakers Bureaus of Otsuka, Allergan, and Lundbeck. HPB has consulted to the Milken Institute. All other authors have no competing interests to declare., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Markers to differentiate depressions of bipolar disorder (BD-Dep) from depressions of major depressive disorder (MDD-Dep), and for more targeted treatments, are critically needed to decrease current high rates of misdiagnosis that can lead to ineffective or potentially deleterious treatments. Distinguishing, and specifically treating the depressions, during the adolescent/young adult epoch is especially important to decrease illness progression and improve prognosis, and suicide, as it is the epoch when suicide thoughts and behaviors often emerge. With differences in functional connectivity patterns reported when BD-Dep and MDD-Dep have been studied separately, this study used a graph theory approach aimed to identify functional connectivity differences in their direct comparison., Methods: Functional magnetic resonance imaging whole-brain functional connectivity (Intrinsic Connectivity Distribution, ICD) measures were compared across adolescents/young adults with BD-Dep (n = 28), MDD-Dep (n = 20) and HC (n = 111). Follow-up seed-based connectivity was conducted on regions of significant ICD differences. Relationships with demographic and clinical measures were assessed., Results: Compared to the HC group, both the BD-Dep and MDD-Dep groups exhibited left-sided frontal, insular, and medial temporal ICD increases. The BD-Dep group had additional right-sided ICD increases in frontal, basal ganglia, and fusiform areas. In seed-based analyses, the BD-Dep group exhibited increased interhemispheric functional connectivity between frontal areas not seen in the MDD-Dep group., Limitations: Modest sample size; medications not studied systematically., Conclusions: This study supports bilateral and interhemispheric functional dysconnectivity as features of BD-Dep that may differentiate it from MDD-Dep in adolescents/young adults and serve as a target for early diagnosis and treatment strategies., Competing Interests: Conflict of interest Dr. Blumberg consulted for the Milken institute. All other authors report no financial relationships with commercial interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: To reduce suicide in females with mood disorders, it is critical to understand brain substrates underlying their vulnerability to future suicidal ideation and behaviors (SIBs) in adolescence and young adulthood. In an international collaboration, grey and white matter structure was investigated in adolescent and young adult females with future suicidal behaviors ( f SB) and ideation ( f SI), and without SIBs ( f nonSIB)., Methods: Structural ( n = 91) and diffusion-weighted ( n = 88) magnetic resonance imaging scans at baseline and SIB measures at follow-up on average two years later (standard deviation, SD = 1 year) were assessed in 92 females [age(SD) = 16.1(2.6) years] with bipolar disorder (BD, 28.3%) or major depressive disorder (MDD, 71.7%). One-way analyses of covariance comparing baseline regional grey matter cortical surface area, thickness, subcortical grey volumes, or white matter tensor-based fractional anisotropy across f SB ( n = 40, 43.5%), f SI ( n = 33, 35.9%) and f nonSIB ( n = 19, 20.6%) groups were followed by pairwise comparisons in significant regions ( p < 0.05)., Results: Compared to f nonSIBs, f SIs and f SBs showed significant decreases in cortical thickness of right inferior frontal gyrus pars orbitalis and middle temporal gyrus, f SIs of left inferior frontal gyrus, pars orbitalis. F SIs and f SBs showed lower fractional anisotropy in left uncinate fasciculus and corona radiata, and f SBs in right uncinate and superior fronto-occipital fasciculi., Conclusions: The study provides preliminary evidence of grey and white matter alterations in brain regions subserving emotional and behavioral regulation and perceptual processing in adolescent and young adult females with mood disorders with, versus without, future SIBs. Findings suggest potential targets to prevent SIBs in female adolescents and young adults., Competing Interests: CONFLICTS OF INTEREST Hilary P. Blumberg received an honorarium for a talk at Aetna. The remaining authors have declared that they have no competing or potential conflicts of interest.

Objective: To examine genomic correlates of conversion to resection (CTR and overall survival (OS) in patients with initially unresectable colorectal liver metastasis (IU-CRLM) treated with combination systemic and hepatic artery infusion (HAI) chemotherapy., Background: In patients presenting with IU-CRLM, combination systemic and HAI chemotherapy enables CTR with associated long-term OS in a subset of patients. Genomic correlates of CTR and OS in IU-CRLM have not been previously explored., Methods: Specimens from IU-CRLM patients receiving systemic/HAI chemotherapy (2003-2017) were submitted for next-generation sequencing. Fisher Exact test assessed associations with CTR, and Kaplan-Meier/Cox methods assessed associations with OS from HAI initiation., Results: Of 128 IU-CRLM patients, 51 (40%) underwent CTR at median 6 months (range: 3-35) from HAI initiation. CTR and persistently unresectable cohorts differed significantly in preoperative systemic chemotherapy exposure, node-positive primary status, and size of largest liver metastasis. Median and 5-year OS was 66 months and 51%. CTR was associated with prolonged survival (time-dependent HR 0.23,95% CI: 0.12-0.46, P < 0.001). The most frequently altered genes were APC (81%), TP53 (77%), and KRAS (37%). Oncogenic mutations in SOX9 and BRAF were associated with CTR. BRAF mutations, any RAS pathway alterations, and co-altered RAS/RAF-TP53 mutations wereassociated with worse survival. Classification and regression tree analysis defined prognostically relevant clusters of genomic risk to reveal co-altered RAS/RAF-TP53 as the highest risk subgroup. Co-altered RAS/RAF-TP53 remained independently associated with worse survival (HR 2.52, 95% CI: 1.37-4.64, P = 0.003) after controlling for CTR, number of liver metastases, and preoperative extrahepatic disease., Conclusions: Distinct genomic profiles are associated with CTR and survival in patients with IU-CRLM treated with HAI/systemic chemotherapy. Presence of SOX9, BRAF , and co-altered RAS/RAF- TP53 mutations are promising biomarkers that, when validated in larger datasets, may impact treatment of IU-CRLM patients., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Despite curative hepatectomy, most colorectal liver metastasis (CRLM) patients relapse locally within 2 years. Genomic predictors for hepatic recurrence are poorly understood. This study was designed to identify genomic signatures for recurrence in resected CRLM patients treated with adjuvant hepatic artery infusion (HAI) and/or systemic (SYS) chemotherapy., Methods: Patients undergoing curative hepatectomy and adjuvant HAI+SYS or SYS between January 2000 and October 2017 with next-generation sequencing data were catalogued. Gene and signaling-level alterations were checked for association with time to any (AR), liver (LR), and extrahepatic recurrence (ER) by using Kaplan-Meier analysis., Results: Of 172 receiving HAI+SYS, 100 patients recurred, with 69 LR and 83 ER. Five- and ten-year LR-free rates were 57% (95% confidence interval [CI] 48-65%) and 51% (95% CI 41-60%), respectively. Five- and 10-year ER-free, rates were 51% (95% CI 43-58%) and 45% (95% CI 36-54%), respectively. More ER was observed with tumors harboring altered KRAS (38% [95% CI 25-50%] vs. 63% [95% CI 53-71%], p-adj = 0.003) and RAS/RAF (36% [95% CI 25-48%] vs. 66% [95% CI 56-74%], p-adj < 0.001) than wild-type. Co-altered RAS/RAF-TP53 was associated with worse AR (26% [95% CI 14-40%] vs. 48% [95% CI 39-57%], p-unadj < 0.001), ER (30% [95% CI 17-45%] vs. 62% [95% CI 53-70%], p-unadj < 0.001), and LR rate (40% [95% CI 24-57%] vs. 70% [95% CI 60-77%], p-unadj = 0.002). On multivariable analysis, controlling for clinical risk score, ablation, margin status, and primary T-stage, co-altered RAS/RAF-TP53 was associated with increased risk for AR (HR = 2.14, 95% CI 1.38-3.31, p-unadj < 0.001), LR (HR = 1.79, 95% CI 1.06-3.02, p-unadj = 0.029), and ER (HR = 2.81, 95% CI 1.78-4.44, p-unadj < 0.001)., Conclusions: Altered KRAS, RAS/RAF, and RAS/RAF-TP53 associated with earlier local and distant recurrence in resected CRLM patients receiving adjuvant HAI+SYS. Co-altered RAS/RAF-TP53 was a novel predictor of LR warranting investigation of whether genomic cooperativity is associated with this relapsing phenotype. Systemic therapies tailored to high-risk tumor biology are needed to reduce distant relapse after hepatectomy., (© 2022. Society of Surgical Oncology.)

Background: There is limited information about the long-term outcomes and patterns of progression in patients who have unresectable, liver-confined hepatocellular carcinoma (HCC) with complete response (CR) to transarterial embolization and do not undergo resection or transplantation (LT)., Methods: A retrospective review analyzed participants in a randomized trial comparing hepatic artery embolization (HAE) and drug-eluting bead transarterial chemoembolization (DEB-TACE) with doxorubicin who had CR according to modified response evaluation criteria in solid tumors (mRECIST). The overall survival (OS), incidence and patterns of progression, and factors associated with progression were assessed., Results: Of the 101 patients in the trial, 37 with CR were included in this study. This cohort had 17 patients treated with HAE (46 %), and 20 patients managed with DEB-TACE (54 %). The median age was 67 years (range, 42-82 years). Most of the cohort were male (86.5 %) and Caucasian (78 %). The median pre-treatment Model for End-Stage Liver Disease (MELD) score was 10, and 70 % of the cohort had Barcelona Clinic Liver Cancer (BCLC) stage B or C. The median follow-up period was 49 months (95 % confidence interval [CI], 9-108 months), and the median OS was 25 months (95 % CI, 18.9-30.9 months). The 3- and 5-year survival rates were respectively 31 % (95 % CI, 16.7-45.9 %) and 18 % (95 % CI, 6.8-32.1 %). The 1- and 2-year cumulative incidences of progression were respectively 76 % (95 % CI, 57.7-86.8 %) and 92 % (95 % CI, 74.5-97.6 %). The most common first site of progression was the previously treated hepatic site or local site (32 %, 12/37). The 3-year cumulative incidence of progression was 65 % (95 % CI, 46.4-78.4 %) for the local site., Conclusion: Patients with advanced-stage HCC and CR to embolization do not have durable responses and experience inevitable disease progression. Most patients with progression have liver-confined disease and should be evaluated for additional consolidative treatments., (© 2022. Society of Surgical Oncology.)

Bipolar disorder (BD) and exposure to childhood maltreatment (CM), which is present at high rates in BD, are both associated with hippocampus and prefrontal cortex structural alterations thought to contribute to clinical features. Gender-related differences are implicated in BD for CM exposure, brain structure and clinical features. However, relationships among these factors in BD are understudied. This study aimed to investigate associations among gender, CM, hippocampus and prefrontal gray matter structure and clinical features in BD. Childhood trauma questionnaire, structured clinical assessments and 3 Tesla structural magnetic resonance imaging were obtained for 236 adults (18-63 years, 32.0 ± 12.6): 119 with BD (58.8% women) and 117 healthy controls (HCs, 50.4% women). Women with BD reported higher CM severity than men with BD and HCs (B=-14.34, 95% confidence intervals (CI)[-22.71,-5.97], p<.001). CM and gender showed a significant interaction for left hippocampus (B=-7.41, 95% CI[-14.10,-0.71], p<.05); CM severity was negatively associated with left hippocampus only in women with BD. In women with BD, CM was associated with post-traumatic stress disorder comorbidity (B = 25.68, 95% CI[15.11,36.25], p<.001). In men with BD, CM severity was associated with lower left frontal pole (B=-0.71, 95% CI[-1.14,-0.28], p<.05) and right superior frontal (B=-17.78, 95% CI[-30.66,-4.90], p<.05) surface area; the latter related to earlier age of first mood symptoms (B = 33.97, 95% CI[7.61, 60.33], p<.05). Findings support gender-related effects of CM on frontotemporal structure and clinical features of BD. The findings bring novel perspectives for gendered pathophysiological models of effects of CM in BD., Competing Interests: Declaration of Competing Interest Dr. Lippard receives funding for a Janssen-sponsored study through University of Texas-Austin. Dr. Blumberg received an honorarium for a talk at Aetna. All other authors declare that they have no conflicts of interest., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Prenatal exposure to testosterone is implicated in the etiology of autism spectrum disorder (ASD). Hypertensive disorders of pregnancy and polycystic ovary syndrome are associated with both hyperandrogenism and increased risk for ASD. We examined whether increased maternal testosterone mediates the relationship between these hyperandrogenic disorders (HDs) during pregnancy and child communication and social skills. Maternal plasma was collected during the second trimester and parent-report measures of child communication and social skills were obtained at 4.5-6.5 years of age from 270 participants enrolled in the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b). Our retrospective frequency-matched cohort study design identified 58 mothers with one or both of the HDs and 58 matched controls. Women diagnosed with an HD who carried a female had higher testosterone levels compared to those carrying a male ( t (56) = -2.70, p = 0.01). Compared to females controls, females born to women with an HD had significantly higher scores on the Social Communication Questionnaire ( t (114) = -2.82, p =0.01). Maternal testosterone partially mediated the relationship between a diagnosis of an HD and SCQ scores among females. These findings point to sex-specific associations of two HDs - hypertensive disorders of pregnancy and polycystic ovary syndrome - on child communication and social skills and a mediating effect of maternal testosterone during pregnancy. Further research is needed to understand placental-mediated effects of maternal testosterone on child brain development and neurodevelopmental outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Firestein, Romeo, Winstead, Goldman, Grobman, Haas, Parry, Reddy, Silver, Wapner and Champagne.)

Objective: Prospective evaluation of 2 clinical-molecular models in patients with unknown pathology who underwent endoscopic ultrasound with fine-needle aspiration (EUS-FNA) for a cystic lesion of the pancreas., Summary of Background Data: Preoperative prediction of histologic subtype (mucinous vs nonmucinous) and grade of dysplasia in patients with pancreatic cystic neoplasms is challenging. Our group has previously published 2 clinical-molecular nomograms for intraductal papillary mucinous neoplasms (IPMN) that incorporated both clinical/radiographic features and cyst fluid protein markers (sFASL, CA72-4, MMP9, IL-4)., Methods: This multiinstitutional study enrolled patients who underwent EUS-FNA for a cystic lesion of the pancreas. Treatment recommendations regarding resection were based on standard clinical, radiographic, and endoscopic features. Predicted probabilities of high-risk IPMN (high-grade dysplasia/invasive cancer) were calculated using the previously developed clinical-molecular nomograms., Results: Cyst fluid was obtained from 100 patients who underwent diagnostic EUS-FNA. Within this group there were 35 patients who underwent resection, and 65 were monitored radiographically. Within the group that underwent resection, 26 had low-risk IPMN or benign non-IPMN lesions, and 9 had high-risk IPMN. Within the surveillance group, no patient progressed to resection or developed cancer after a median follow-up of 12months (range: 0.5-38). Using the clinical/radiographic nomogram alone, 2 out of 9 patients with high-risk IPMN had a predicted probability >0.5. In the clinical-molecular models, 6 of 9 patients in model 1, and 6 of 9 in model 2, had scores >0.5., Conclusions: This prospective study of patients with unknown cyst pathology further demonstrates the importance of cyst fluid protein analysis in the preoperative identification of patients with high-risk IPMN. Longer follow-up is necessary to determine if this model will be useful in clinical practice., Competing Interests: The authors report no conflicts of interest, (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Precise planning and evaluation of the fibula bone are necessary if immediate endosseous implant placement is considered. Limited information is available on the anatomical dimensions or density of fibula used in mandibular reconstructions. This study aimed to describe the morphology and dimensions of the fibula used to reconstruct segmental mandibular defects and contrast the findings with the native mandible., Methods: A retrospective analysis was performed of patients who underwent segmental mandibulectomy reconstructed with osteocutaneous fibula flaps and had at least one postoperative computed tomography scan. Fibula cross sectional dimensions and densities were evaluated with three-dimensional software. Radiographic measurements were obtained from the contralateral mandible medial to the first molar for comparison., Results: Four hundred seventy-seven fibula cross sections from 159 segments were evaluated. Cross-sectional oval, quadrilateral, triangular, and pentagonal shapes differed significantly in proportion (p < 0.001). Thirty-eight percent of segments (95 percent CI, 30 to 46 percent) had differences in cross-section height greater than 1 mm (p < 0.001). Between segments within the same patient, the median height difference was 1.58 mm (range, 0.14 to 6 mm). The superior cortex density was significantly higher for the fibula than the native mandible; however, the medullary space density was significantly lower (p < 0.001)., Conclusions: The current study comprises the most comprehensive description of fibula morphology in mandibular reconstructions and highlights the significant variability that exists. The findings provide justification for the added time and cost of computer-aided design and computer-aided manufacturing in centers interested in performing immediate dental implant placement, as the technology provides the necessary precision and accuracy., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Objectives: Identifying hubs of brain dysfunction in adolescents and young adults with Bipolar I Disorder (BD AYA ) could provide targets for early detection, prevention, and treatment. Previous neuroimaging studies across mood states of BD AYA are scarce and often examined limited brain regions potentially prohibiting detection of other important regions. We used a data-driven whole-brain Intrinsic Connectivity Distribution (ICD) approach to investigate dysconnectivity hubs across mood states in BD AYA ., Methods: Functional magnetic resonance imaging whole-brain ICD data were investigated for differences across four groups: BD AYA -depressed (n = 22), BD AYA -euthymic (n = 45), BD AYA -elevated (n = 24), and healthy controls (HC, n = 111). Clusters of ICD differences were assessed for regional dysconnectivity and mood symptom relationships. Analyses were also performed for BD AYA overall (vs. HC) ICD differences persisting across mood states., Results: ICD was higher in the BD AYA- depressed group than other groups in bilateral ventral/rostral/dorsal prefrontal cortex (PFC) and right lenticular nucleus (LN) (p corrected  <0.05). In BD AYA -depressed, functional connectivity (FC) was increased between these regions with their contralateral homologues and PFC-medial temporal FC was more negative (p < 0.005). PFC-related findings correlated with depression scores (p < 0.05). The overall BD AYA group showed ICD increases in more ventral left PFC and right cerebellum, present across euthymia and acute mood states., Conclusions: This ICD approach supports a PFC hub of inter- and intra-hemispheric frontotemporal dysconnectivity in BD AYA with potential trait features and disturbances of higher magnitude during depression. Hubs were also revealed in LN and cerebellum, less common foci of BD research. The hubs are potential targets for early interventions to detect, prevent, and treat BD., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Elevated aggression and impulsivity are implicated in Bipolar Disorder (BD); however, relationships between these behavioral constructs have not been clarified, which can lead to misconceptions with negative consequences including stigma and adverse outcomes including suicide. The study aimed to clarify brain-based distinctions between the two constructs and their associations to risk factors, symptoms and suicide thoughts and behaviors., Methods: Self-rated Brown-Goodwin Aggression (BGA) and Barratt Impulsiveness Scale (BIS) scores were compared between adults with BD (n = 38, 74% female) and healthy controls (HC, n = 29, 64% female). Relationships were examined between BGA and BIS with childhood trauma questionnaire (CTQ), mood, comorbidities, and magnetic resonance imaging gray matter volume (GMV) assessments., Results: In BD, BGA and BIS total scores were both elevated and associated with childhood maltreatment (CM), particularly emotional CM, depression, substance use disorders (SUDs) and suicide attempts (SAs). BGA scores were increased by items corresponding to dysregulation of emotional and social behavior and associated with elevated mood states and suicide ideation and GMV decreases in bilateral orbitofrontal cortex and left posterior insula brain regions, previously associated with these behaviors and clinical features. BIS motor impulsiveness scores were associated with GMV decreases in anterior cingulate cortex implicated in mood and behavioral dyscontrol., Limitations: modest sample size, self-reports CONCLUSIONS: The findings suggest separable brain-based domains of dysfunction in BD of motor impulsiveness versus emotionally dysregulated feelings that are primarily self-directed. Both domains are associated with suicide behavior and modifiable risk factors of CM, depression and SUDs that could be targeted for prevention., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Fetal exposure to testosterone may contribute to vulnerability for autism spectrum disorder (ASD). It is hypothesized that placental aromatase prevents fetal exposure to maternal testosterone, however, this pathway and the implications for child neurodevelopment have not been fully explored. We examined the relationships between prenatal maternal testosterone and estradiol at 19.2 ± 1.3 weeks, cord blood testosterone and estradiol at birth, placental aromatase mRNA expression, and neurodevelopment using the Social Communication Questionnaire (SCQ), the Behavioral Assessment System for Children, 3rd Edition (BASC-3), and the Empathizing Quotient for Children (EQ-C) at 4.5-6.5 years of age in a sample of 270 Nulliparous-Mothers-to-be (nuMoM2b) study participants. Maternal testosterone levels were positively associated with SCQ scores, but the association was not significant after adjusting for maternal age at delivery, nor was there a significant interaction with sex. Maternal estradiol levels were negatively associated with BASC-3 Clinical Probability scores among males (n = 139). We report a significant interaction effect of cord blood testosterone and fetal sex on both total SCQ scores and t-scores on the Developmental Social Disorders subscale. Placental aromatase was not associated with any neurodevelopmental or hormone measure, but under conditions of low placental aromatase expression, high maternal testosterone was positively associated with SCQ scores in males (n = 46). No other associations between hormone levels and neurodevelopment were significant. Our findings provide a foundation for further investigation of the mechanisms through which maternal sex hormones and placental steroidogenesis may affect fetal hormone production and neurobehavior., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: Nivolumab + ipilimumab (nivo + ipi) is highly efficacious but has high toxicity. Standard treatment in advanced melanoma is four doses of nivo + ipi followed by nivo alone. Whether four doses of nivo + ipi are needed is unclear., Methods: The Adaptively Dosed ImmunoTherapy Trial (ADAPT-IT) study (NCT03122522) is a multicenter, single-arm phase II clinical trial. Patients received two doses of nivo (1 mg/kg) + ipi (3 mg/kg) followed by a computed tomography scan at week 6. Patients without new lesions or index lesion tumor growth of > 4% had protocol-defined early favorable antitumor effect (FATE) and ceased nivo + ipi, transitioning to nivo monotherapy. Patients without FATE at week 6 received the standard third and fourth doses of nivo + ipi followed by nivo monotherapy. The primary end point was response rate by RECIST 1.1 at week 12. Secondary end points included additional efficacy assessments and safety., Results: Sixty patients were enrolled; 41 patients (68%) had FATE at week 6 and met criteria for stopping nivo + ipi. Best overall response rates by RECIST at week 12 or any time afterward were 48% (95% CI, 35 to 62) and 58% (95% CI, 45 to 71), respectively. With a median follow-up of 25 months, the estimated 18-month progression-free survival and overall survival are 52% and 80%, respectively. Fifty seven percent of patients had grade 3-5 treatment-related toxicity., Conclusion: The efficacy and toxicity of standard four dose nivo + ipi induction therapy in melanoma is likely driven by the first two doses. An interim computed tomography scan after two doses guided cessation of combination dosing and identified almost all responders. Longer follow-up and further study are needed to fully understand the implications of a shortened induction course of nivo + ipi., Competing Interests: Michael A. PostowConsulting or Advisory Role: Bristol Myers Squibb, Novartis, Array BioPharma, NewLink Genetics, Incyte, Merck, Eisai, PfizerResearch Funding: Bristol Myers Squibb (Inst), Novartis (Inst), Array BioPharma (Inst), Infinity Pharmaceuticals (Inst), Regenix (Inst), Merck (Inst), AstraZeneca/MedImmune (Inst) Debra A. GoldmanEmployment: RegeneronStock and Other Ownership Interests: Johnson & Johnson Alexander N. ShoushtariConsulting or Advisory Role: Immunocore, Bristol Myers SquibbResearching Funding: Immunocore, Bristol Myers Squibb, Xcovery, Polaris, Novartis (Inst), Pfizer (Inst)Patents, Royalties, Other Intellectual Property: UpToDate Allison Betof WarnerHonoraria: LG ChemConsulting or Advisory Role: Nanbiotix, Iovance Biotherapeutics, Novartis, Shanghai Jo’Ann Medical Technology, BluePath Solutions, PfizerResearch Funding: Leap Therapeutics Margaret K. CallahanEmployment: Bristol-Myers Squibb (I), Celgene (I), Kleo Pharmaceuticals (I), Bristol-Myers Squibb (I)Consulting or Advisory Role: AstraZeneca, Moderna Therapeutics, Merck, ImmunocoreResearching Funding: Bristol Myers Squibb (Inst)Other Relationship: Clinical Care Options, Potomac Center for Medical Education Omar EtonSpeakers’ Bureau: MerckResearching Funding: Bristol Myers Squibb (Inst) Suresh G. NairStock and Other Ownership Interests: Moderna Therapeutics, Novavax, Biotech, Gilead SciencsResearch Funding: Bristol-Myers Squibb, Merck, Nektar (Inst) Katherine S. PanageasStock and Other Ownership Interests: AstraZeneca, Pfizer, Sunesis Pharmaceuticals Jedd D. WolchokStock and Other Ownership Interests: Tizona Therapeutics, Inc, Adaptive Biotechnologies, Imvaq Therapeutics, Beigene, Linnaeus Therapeutics, Arsenal IO, Geogiamune, LLC, Maverick Therapeutics, Apricity Therapeutics, Trieza TherapeuticsConsulting or Advisory Role: Bristol-Myers Squibb, Merck, Sellas Life Sciences, Lilly, Tizona Therapeutics, Inc,, Amgen, Chugai Pharma, Adaptive Biotechnologies, Ascentage Pharma, PsiOxus Therapeutics, F-Start Biotechnology, Surface Biotechnology, Apricity Therapeutics, PsiOxus Therapeutics, F-Star Biotechnology, Surface Oncology, Apricity Therapeutics, PsiOxus Therapeutics, Astellas Pharma, Recepta Biopharma, Arsenal IO, Boehringer Ingelheim, AstraZeneca, Daiichi Sankyo,Inc, Dragonfly Therapeutics, Geogiamune, Kyowa Kirin Pharmaceutical, Maverick Therapeutics, Werewolf Therapeutics, Trishula Therapeutics, Idera, Imvq Therapeutics, Biscara TherapeuticsResearch Funding: Bristol Myers Squibb (Inst), Genentech/Roche (Inst), Merck Sharp & Dohme (Inst)Patents, Royalties, Other Intellectual Property: I am a co-inventor on an issued patent for DNA vaccines for treatment for cancer in companion animals, I am a co-inventor on a patent for use of oncolytic Newcaste Disease virus, I am a co-inventor and receive royalties for a blood test for monitoring myeloid derived suppressor cells. I am co-inventor and receive royalties for a petent for immune modulating antibododies. I am a co-inventor on a patent for CAR+ T cells targeting differentiation antigens as means to treat cancer. I am a co-inventor on a patent for Anti-CD40 agonist mAb fused to Monophosphory Lipid A (MPL) for cancer therapy, Alphavirus Replicon Particles Expressing TRP2, Engineered Vaccinia Viruses for Cancer Immunotherapy, Recombinant Poxviruses for Cancer Immunotherapy Paul B. ChapmanConsulting or Advisory Role: Merck, Pfizer, Black Diamond TherapeuticsResearch Funding: Pfizer, NCI (Inst), GenentechNo other potential conflicts of interest were reported.

Purpose: Preoperative radiographic differentiation of mucinous cystic neoplasms (MCN) and simple cysts (SLC) of the liver is challenging. Previous data have demonstrated that the finding of septations arising from the cyst wall without indentation on cross-sectional imaging is associated with MCN. We aim to assess whether this radiographic feature is diagnostic of MCN., Methods: A prospectively maintained database was queried for patients with a preoperative diagnosis of a cystic liver lesion who subsequently underwent operative intervention. The feature of septations without indentation of the cyst wall was evaluated on cross-sectional imaging obtained within 3 months of operation. Imaging was independently evaluated by three radiologists blinded to pathology and interobserver agreement was compared to assess the diagnostic accuracy of this feature as well as the overall likelihood of the lesion representing a MCN., Results: There were 95 patients who met inclusion criteria; 80 (84%) had SLC on pathology, while 15 (16%) had MCN. Presence of septa without indentation of cyst wall had high sensitivity (range 80-87%), but low specificity (range 48-66%). Interobserver percent agreement (PA) was 51% [κ = 0.35 (95% CI 0.22-0.47)]. Sensitivity among the three radiologists ranged between 20 and 80% and specificity between 71 and 91% for the likelihood of the lesion representing MCN versus SLC, with an area under the curve (AUC) of 0.67-0.79; however, interobserver agreement was fair [κ = 0.40 (95% CI 0.25-0.55), PA = 67%]., Conclusion: The presence of septations without indentation of cyst wall demonstrates adequate sensitivity to differentiate MCN and SLC. However, there is variability for detection of this feature and therefore, it alone is of limited clinical value., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Patients with locally advanced pancreatic adenocarcinoma (PDAC) receive induction chemotherapy with or without radiation, with the goal of R0 resection and improving survival. Herein, we evaluate the outcomes of patients who presented with Stage III PDAC and received induction FOLFIRINOX., Methods: An institutional database was queried for consecutive patients who received induction FOLFIRINOX for locally unresectable PDAC between 2010 and 2016. Clinical and radiographic parameters were assessed pre- and posttreatment, and clinical outcomes were evaluated., Results: There were 200 patients who met the inclusion criteria. The median number of cycles of FOLFIRINOX was 8, 70% (n = 140) received radiation, and 18% (n = 36) underwent resection. Median overall survival (OS) in resected patients was 36 months (95% confidence interval [CI]: 24-56), and this group had improved OS compared to patients that did not undergo resection (hazard ratio (95% CI): 0.41 (0.26-0.64), p < 0.001). Patients (n = 112) who did not progress on induction therapy but remained unresectable had a median OS of 23.9 months (95% CI: 21.1-25.4)., Conclusion: Nearly 20% of patients with locally advanced PDAC responded sufficiently to induction FOLFIRINOX to undergo resection, which was associated with improved OS compared to patients that did not undergo resection. Patients with stable disease who remain unresectable represent a group of patients with locally advanced PDAC who may benefit from optimization of additional nonoperative treatment., (© 2021 Wiley Periodicals LLC.)

Brain targets to lower the high risk of suicide in Bipolar Disorder (BD) are needed. Neuroimaging studies employing analyses dependent on regional assumptions could miss hubs of dysfunction critical to the pathophysiology of suicide behaviors and their prevention. This study applied intrinsic connectivity distribution (ICD), a whole brain graph-theoretical approach, to identify hubs of functional connectivity (FC) disturbances associated with suicide attempts in BD. ICD, from functional magnetic resonance imaging data acquired while performing a task involving implicit emotion regulation processes important in BD and suicide behaviors, was compared across 40 adults with BD with prior suicide attempts (SAs), 49 with BD with no prior attempts (NSAs) and 51 healthy volunteers (HVs). Areas of significant group differences were used as seeds to identify regional FC differences and explore associations with suicide risk-related measures. ICD was significantly lower in SAs than in NSAs and HVs in bilateral ventromedial prefrontal cortex (vmPFC) and right anterior insula (RaIns). Seed connectivity revealed altered FC from vmPFC to bilateral anteromedial orbitofrontal cortex, left ventrolateral PFC (vlPFC) and cerebellum, and from RaIns to right vlPFC and temporopolar cortices. VmPFC and RaIns ICD were negatively associated with suicidal ideation severity, and vmPFC ICD with hopelessness and attempt lethality severity. The findings suggest that SAs with BD have vmPFC and RaIns hubs of dysfunction associated with altered FC to other ventral frontal, temporopolar and cerebellar cortices, and with suicidal ideation, hopelessness, and attempt lethality. These hubs may be targets for novel therapeutics to reduce suicide risk in BD., (© 2021. The Author(s).)

Hepatitis C in children is on the rise due to perinatal transmission from infected mothers, and high-risk practices in adolescents and young adults. Prevalence remains underestimated because children at high risk are often not screened. Treatment has evolved over the past decade with the advent of new drugs, and global elimination is now possible. Direct-acting antiviral combinations are safe and effective, with sustained viral suppression rate >90%, and Food and Drug Administration-approved for children ≥3 years old. Although challenging, efficient screening and treatment of chronic hepatitis C virus early is cost-effective and reduces burden of disease and its complications., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To evaluate the influence of consensus guidelines on the management of intraductal papillary mucinous neoplasms (IPMN) and the subsequent changes in pathologic outcomes., Background: Over time, multiple guidelines have been developed to identify high-risk IPMN. We hypothesized that the development and implementation of guidelines should have increased the percentage of resected IPMN with high-risk disease., Methods: Memorial Sloan-Kettering (MSK), Johns Hopkins (JH), and Massachusetts General Hospital (MGH) databases were queried for resected IPMN (2000-2015). Patients were categorized into main-duct (MD-IPMN) versus branch-duct (BD-IPMN). Guideline-specific radiographic/endoscopic features were recorded. High-risk disease was defined as high-grade dysplasia/carcinoma. Fisher's exact test was used to detect differences between institutions. Logistic regression evaluated differences between time-points [preguidelines (pre-GL, before 2006), Sendai (SCG, 2006-2012), Fukuoka (FCG, after 2012)]., Results: The study included 1210 patients. The percentage of BD-IPMN with ≥1 high-risk radiographic feature differed between centers (MSK 69%, JH 60%, MGH 45%; P < 0.001). In MD-IPMN cohort, the presence of radiographic features such as solid component and main pancreatic duct diameter ≥10 mm also differed (solid component: MSK 38%, JH 30%, MGH 18%; P < 0.001; duct ≥10 mm: MSK 49%, JH 32%, MGH 44%; P < 0.001). The percentage of high-risk disease on pathology, however, was similar between institutions (BD-IPMN: P = 0.36, MD-IPMN: P = 0.48). During the study period, the percentage of BD-IPMN resected with ≥1 high-risk feature increased (52% pre-GL vs 67% FCG; P = 0.005), whereas the percentage of high-risk disease decreased (pre-GL vs FCG: 30% vs 20%). For MD-IPMN, there was not a clear trend towards guideline adherence, and the rate of high-risk disease was similar over the time (pre-GL vs FCG: 69% vs 67%; P = 0.63)., Conclusion: Surgical management of IPMN based on radiographic criteria is variable between institutions, with similar percentages of high-risk disease. Over the 15-year study period, the rate of BD-IPMN resected with high-risk radiographic features increased; however, the rate of high-risk disease decreased. Better predictors are needed., Competing Interests: The authors declare no conflict of interests., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Social rhythm irregularities are associated with increased bipolar disorder symptoms and suicide risk. This study was the first to examine the feasibility and acceptability of a 12-week social rhythm therapy (SRT) delivered predominantly via telehealth (three in-person sessions, nine via video teleconferencing) to adolescents and young adults with bipolar disorder. The primary aim was to determine the feasibility and acceptability of SRT delivered predominantly via telehealth. Secondary aims were to explore the intervention's impacts on social rhythm regularity, mood symptoms, and suicide propensity., Methods: Thirteen adolescents and young adults with bipolar disorder received a modified SRT called Brain Emotion circuitry-targeted Self-Monitoring And Regulation Therapy for Daily Rhythms (BE-SMART-DR) administered mostly remotely, adjunctive to treatment as usual. Retention rates, client satisfaction, therapeutic alliance, and pre- to postintervention changes in social rhythm regularity, mood symptoms, and suicide propensity were assessed., Results: BE-SMART-DR was associated with high retention rates (77%), high mean±SD scores on the Client Satisfaction Questionnaire (29.4±2.7), and high participant global scores on the Working Alliance Inventory (231.3±8.1), indicative of strong therapeutic alliance. Secondary outcome measures on social rhythm irregularities, mood symptoms, and suicide propensity decreased from pre- to posttherapy. Increased social rhythm regularity was associated with reduced suicide propensity after analyses were controlled for reductions in mood symptoms., Conclusions: These preliminary results indicate that SRT delivered largely by telemedicine is feasible and acceptable. The intervention appeared to reduce mood symptoms, and suicide propensity independent of mood symptoms, among adolescents and young adults with bipolar disorder.

Objective: Recurrent genomic alterations in clear cell renal cell carcinoma (ccRCC) have been associated with treatment outcomes; however, current preoperative predictive models do not include known genetic predictors. We aimed to explore the value of common somatic mutations in the preoperative prediction of metastatic disease among patients treated for localized ccRCC., Materials and Methods: After obtaining institutional review board approval, data of 254 patients with localized ccRCC treated between 2005 and 2015 who underwent genetic sequencing was collected. The mutation status of VHL, PBRM1, SETD2, BAP1 and KDM5C were evaluated in the nephrectomy tumor specimen, which served as a proxy for biopsy mutation status. The Raj et al. preoperative nomogram was used to predict the 12-year metastatic free probability (MFP). The study outcome was MFP; the relationship between MFP and mutation status was evaluated with Cox-regression models adjusting for the preoperative nomogram variables (age, gender, incidental presentation, lymphadenopathy, necrosis, and size)., Results: The study cohort included 188 males (74%) and 66 females (26%) with a median age of 58 years. VHL mutations were present in 152/254 patients (60%), PBRM1 in 91/254 (36%), SETD2 in 32/254 (13%), BAP1 in 19/254 (8%), and KDM5C in 19/254 (8%). Median follow-up for survivors was 8.1 years. Estimated 12-year MFP was 70% (95% CI: 63%-75%). On univariable analysis SETD2 (HR: 3.30), BAP1 (HR: 2.44) and PBRM1 (HR: 1.78) were significantly associated with a higher risk of metastases. After adjusting for known preoperative predictors in the existing nomogram, SETD2 mutations remained associated with a higher rate of metastases after nephrectomy (HR: 2.09, 95% CI: 1.19-3.67, P = 0.011)., Conclusion: In the current exploratory analysis, SETD2 mutations were significant predictors of MFP among patients treated for localized ccRCC. Our findings support future studies evaluating genetic alterations in preoperative renal biopsy samples as potential predictors of treatment outcome., Competing Interests: Conflict of interest and disclosure Oguz Akin holds stock options and serves as a scientific advisor for Ezra AI, Inc., which is developing Artificial Intelligence algorithms and software unrelated to the research being reported., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Robotic-assisted minimally invasive esophagectomy (RAMIE) is a safe alternative to open esophagectomy (OE). However, differences in quality of life (QOL) after these procedures remain unclear. We previously reported short-term QOL outcomes after RAMIE and OE and describe here our results from 2 years of follow-up., Methods: We conducted a prospective, nonrandomized trial of patients with esophageal cancer undergoing transthoracic resection by RAMIE or OE at a single institution. The primary outcomes were patient-reported QOL, measured by the Functional Assessment of Cancer Therapy-Esophageal (FACT-E), and pain, measured by the Brief Pain Inventory (BPI). Generalized linear models were used to assess the relationship between QOL outcomes and surgery cohort. P values were adjusted (P-adj) within each model using the false discovery rate correction., Results: Esophagectomy was performed in 170 patients (106 OE and 64 RAMIE). The groups did not differ significantly by any measured clinicopathologic variables. After covariates were controlled for, FACT-E scores were higher in the RAMIE cohort than in the OE cohort (parameter estimate [PE], 6.13; P-adj = .051). RAMIE was associated with higher esophageal cancer subscale (PE, 2.72; P-adj = .022) and emotional well-being (PE, 1.25; P-adj = .016) scores. BPI pain severity scores were lower in the RAMIE cohort than in the OE cohort (PE, -0.56; P-adj = .005), but pain interference scores did not differ significantly between groups (P-adj = .11)., Conclusions: During 2 years of follow-up, RAMIE was associated with improved patient-reported QOL, including esophageal symptoms, emotional well-being, and decreased pain, compared with OE., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Neoadjuvant chemotherapy (NAC) is an integral component of T4 breast cancer (BCa) treatment. We compared response to NAC for T4 BCa in the U.S. and Nigeria to direct future interventions., Materials and Methods: Cross-sectional retrospective analysis included all patients with non-metastatic T4 BCa treated from 2010 to 2016 at Memorial Sloan Kettering Cancer Center (New York, New York) and Obafemi Awolowo University Teaching Hospitals Complex (Ile Ife, Nigeria). Pathologic complete response (pCR) and survival were compared and factors contributing to disparities evaluated., Results: Three hundred and eight patients met inclusion criteria: 157 (51%) in the U.S. and 151 (49%) in Nigeria. All U.S. patients received NAC and surgery compared with 93 (62%) Nigerian patients. Fifty-six out of ninety-three (60%) Nigerian patients completed their prescribed course of NAC. In Nigeria, older age and higher socioeconomic status were associated with treatment receipt. Fewer patients in Nigeria had immunohistochemistry performed (100% U.S. vs. 18% Nigeria). Of those with available receptor subtype, 18% (28/157) of U.S. patients were triple negative versus 39% (9/23) of Nigerian patients. Overall pCR was seen in 27% (42/155) of U.S. patients and 5% (4/76) of Nigerian patients. Five-year survival was significantly shorter in Nigeria versus the U.S. (61% vs. 72%). However, among the subset of patients who received multimodality therapy, including NAC and surgery with curative intent, 5-year survival (67% vs. 72%) and 5-year recurrence-free survival (48% vs. 61%) did not significantly differ between countries., Conclusion: Addressing health system, socioeconomic, and psychosocial barriers is necessary for administration of complete NAC to improve BCa outcomes in Nigeria., Implications for Practice: This cross-sectional retrospective analysis of patients with T4 breast cancer in Nigeria and the U.S. found a significant difference in pathologic complete response to neoadjuvant chemotherapy (5% Nigeria vs. 27% U.S.). Five-year survival was shorter in Nigeria, but in patients receiving multimodality treatment, including neoadjuvant chemotherapy and surgery with curative intent, 5-year overall and recurrence-free survival did not differ between countries. Capacity-building efforts in Nigeria should focus on access to pathology services to direct systemic therapy and promoting receipt of complete chemotherapy to improve outcomes., (© 2021 AlphaMed Press.)

Background and Aim: Genetic alterations in intrahepatic cholangiocarcinoma (iCCA) are increasingly well characterized, but their impact on outcome and prognosis remains unknown., Approach and Results: This bi-institutional study of patients with confirmed iCCA (n = 412) used targeted next-generation sequencing of primary tumors to define associations among genetic alterations, clinicopathological variables, and outcome. The most common oncogenic alterations were isocitrate dehydrogenase 1 (IDH1; 20%), AT-rich interactive domain-containing protein 1A (20%), tumor protein P53 (TP53; 17%), cyclin-dependent kinase inhibitor 2A (CDKN2A; 15%), breast cancer 1-associated protein 1 (15%), FGFR2 (15%), polybromo 1 (12%), and KRAS (10%). IDH1/2 mutations (mut) were mutually exclusive with FGFR2 fusions, but neither was associated with outcome. For all patients, TP53 (P < 0.0001), KRAS (P = 0.0001), and CDKN2A (P < 0.0001) alterations predicted worse overall survival (OS). These high-risk alterations were enriched in advanced disease but adversely impacted survival across all stages, even when controlling for known correlates of outcome (multifocal disease, lymph node involvement, bile duct type, periductal infiltration). In resected patients (n = 209), TP53mut (HR, 1.82; 95% CI, 1.08-3.06; P = 0.03) and CDKN2A deletions (del; HR, 3.40; 95% CI, 1.95-5.94; P < 0.001) independently predicted shorter OS, as did high-risk clinical variables (multifocal liver disease [P < 0.001]; regional lymph node metastases [P < 0.001]), whereas KRASmut (HR, 1.69; 95% CI, 0.97-2.93; P = 0.06) trended toward statistical significance. The presence of both or neither high-risk clinical or genetic factors represented outcome extremes (median OS, 18.3 vs. 74.2 months; P < 0.001), with high-risk genetic alterations alone (median OS, 38.6 months; 95% CI, 28.8-73.5) or high-risk clinical variables alone (median OS, 37.0 months; 95% CI, 27.6-not available) associated with intermediate outcome. TP53mut, KRASmut, and CDKN2Adel similarly predicted worse outcome in patients with unresectable iCCA. CDKN2Adel tumors with high-risk clinical features were notable for limited survival and no benefit of resection over chemotherapy., Conclusions: TP53, KRAS, and CDKN2A alterations were independent prognostic factors in iCCA when controlling for clinical and pathologic variables, disease stage, and treatment. Because genetic profiling can be integrated into pretreatment therapeutic decision-making, combining clinical variables with targeted tumor sequencing may identify patient subgroups with poor outcome irrespective of treatment strategy., (© 2021 by the American Association for the Study of Liver Diseases.)

Background: Morbidity after hepatectomy remains a significant, potentially preventable, outcome. Understanding the pattern of complications and rescue pathways is critical for the development of targeted initiatives intended to salvage patients after operative morbidity., Study Design: Patients undergoing liver resection from 1991 to 2018 at a single institution were analyzed. Failure to rescue (FTR) was defined as percentage of deaths in patients with a complication within 30 days. Generalized estimating equations with log-link function assessed associations between clinical characteristics and major complications and between complications at fewer than 30 days and 30 to 90 days. Logistic regression assessed associations between complications and FTR., Results: A total of 6,191 patients and 6,668 operations were identified, of which 55.6% were performed for management of metastatic colorectal cancer. Major complications (grade ≥3) occurred in 20.2% of operations (1,346 of 6,668). Ninety-day mortality was 2.2%. The most common complication was intra-abdominal abscess at 9.0% (95% CI, 8.3% to 9.7%). Ten percent of patients with a complication at 30 days had another complication between 30 and 90 days compared with 2% without an early complication (odds ratio [OR] 5.09; 95% CI, 3.97 to 6.54; p < 0.001). FTR for liver failure, cardiac arrest, abscess, and hemorrhage was 36%, 56%, 3%, and 6%, respectively. Risk of 90-day mortality was higher in patients with liver failure (53% vs 2%; OR 61.42; 95% CI, 37.47 to 100.67; p < 0.001), cardiac arrest (69% vs 2%; OR 96.95; 95% CI, 33.23 to 283.80; p < 0.001), hemorrhage (11% vs 2%; OR 5.51; 95% CI, 2.59 to 11.73; p < 0.001), and abscess (7% vs 2%; OR 4.05; 95% CI, 2.76 to 5.94; p < 0.001) compared with those without these complications., Conclusions: Morbidity after hepatectomy is frequent despite low mortality. This study identifies targets for improvement in morbidity and failure to rescue after hepatectomy. Efforts to improve recognition and intervention for infections and early complications are needed to improve outcomes., (Copyright © 2021 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate predictors associated with post-treatment biopsy outcomes after stereotactic body radiotherapy (SBRT) for localized prostate cancer., Materials and Methods: 257 patients treated with prostate SBRT to dose levels of 32.5 Gy to >40 Gy in 5-6 fractions underwent a post-treatment biopsy performed approximately two years after treatment to evaluate local control status. 73 had% intermediate-risk disease (n = 187) and the remaining 17% (n = 43) and 10% (n = 27) had low-risk and high-risk disease, respectively., Results: The incidence of positive, negative, and treatment-effect post-treatment biopsies were 15.6%, 57.6%, and 26.8%, respectively. The incidence of a positive biopsy according to dose was 37.5% (n = 9/24), 21.4% (n = 6/28), 19.4% (n = 6/31), and 10.9% (n = 19/174) for 32.5 Gy, 35 Gy, 37.5 Gy, and >40 Gy, respectively. In a multivariable model, patients treated with SBRT doses of <40 Gy and those with unfavorable-intermediate-risk or high-risk disease had higher likelihood of a positive post-treatment biopsy. A positive post-SBRT biopsy was associated with a significantly higher likelihood of subsequent PSA relapse at five years (Positive biopsy: 57%, 95% CI: 29-77% compared to negative biopsy: 7%, 95% CI: 3-14%; p < 0.001)., Conclusion: Based on two-year post-SBRT biopsies, excellent tumor control was achieved when dose levels of 40 Gy or higher were used. Standard SBRT dose levels of 35-37.5 Gy were associated with a higher likelihood of a positive post-treatment biopsy. Two-year positive post-treatment biopsies pre-dated the development of PSA failure in the majority of patients., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: ROS1 fusions are oncogenic drivers in 1% to 3% of NSCLCs. The activity of immune checkpoint inhibitor (ICI) monotherapy or in combination with chemotherapy (chemotherapy with ICI [chemo-ICI]) in these tumors and their immunophenotype have not been systematically described., Methods: In this multi-institutional retrospective study, tumor programmed death-ligand 1 (PD-L1) expression and tumor mutational burden (TMB) were evaluated in patients with ROS1- rearranged NSCLC. Time-to-treatment discontinuation (TTD) and objective response rate (ORR) (Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1) were calculated for patients treated with ICI or chemo-ICI in the metastatic setting., Results: A total of 184 patients were identified. Among 146 assessable cases, PD-L1 expression was less than 1% in 60 (41%), 1% to 49% in 35 (24%), and greater than or equal to 50% in 51 tumors (35%). Of 100 (92%) TMB-assessable tumors, 92 had less than 10 mutations per megabase. TMB was significantly lower for ROS1- rearranged tumors (n = 97) compared with tumors with EGFR (n = 1250) or KRAS alterations (n = 1653) and all other NSCLC tumors (n = 2753) evaluated with Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (median TMB = 2.6 versus 3.5, 7.0, and 6.1 mutations per megabase, p < 0.001). Among patients treated with ICI, median TTD was 2.1 months (95% confidence interval [CI]: 1.0-4.2 mo; n = 28) and ORR 13% (2 of 16 RECIST-assessable; 95% CI: 2%-38%). Among patients treated with chemo-ICI, median TTD was 10 months (95% CI: 4.7-14.1 mo; n = 11) and ORR 83% (5 of 6 RECIST-assessable; 95% CI: 36%-100%). There was no difference in PD-L1 expression ( p  = 0.91) or TMB ( p  = 0.83) between responders and nonresponders., Conclusions: Most ROS1- rearranged NSCLCs have low PD-L1 expression and TMB. The activity of ICI in these tumors is modest. In contrast, chemo-ICI can achieve meaningful activity., (© 2021 The Authors.)

Purpose: Malignant bowel obstruction (MBO) is common in advanced GI cancer, and MBO management, including drainage percutaneous endoscopic gastrostomy (dPEG), is palliative. How patients understand the goals of dPEG and its impact on disease is inadequately understood in the literature. Therefore, we analyzed these issues in patients with GI cancer., Methods: Demographics, clinical variables, and patient outcomes were abstracted from the medical record. Illness understanding and future expectations were retrieved from palliative care notes. We described additional treatment and outcomes after dPEG and estimated overall survival (OS)., Results: From January 2015 to June 2017, 125 admitted patients with metastatic GI cancer underwent dPEG for MBO. Cancers were most commonly colorectal (34%) and pancreatic/ampullary (25%). During the dPEG admission, 32% (40 of 125) of patients had a palliative care consultation, and 22% (28 of 125) were asked about illness understanding and future expectations. All (28 of 28) reported good understanding of the advanced nature of their disease, but few were accurate about prognosis given their stage IV disease (10 of 28). Of the 117 (94%) discharged, 13% (15 of 117) received additional chemotherapy, which rarely prevented progression; half (63 of 117) had a do-not-resuscitate order; and most (101 of 117) were enrolled in hospice at death. Median time to death was 37 days (95% CI, 29 to 45 days); 6-month OS was 3.7% (95% CI, 1.2% to 8.4%)., Conclusion: dPEGs are placed close to end of life in patients with advanced GI cancer. A minority of patients receive additional chemotherapy post-dPEG. Many have adequate disease understanding, but chemotherapy benefit is low, and future expectations vary. This may be an opportunity for improved communication regarding palliative procedures in advanced cancer.