Faculty Bibliography

INTRODUCTION:With 116 000 people waiting for transplants and 8000 patients dying annually on waiting lists, the United States has a considerable organ shortage. An insufficient number of Americans have registered to become organ donors when obtaining driver's licenses or ID cards. Across states, there is considerable variability in organ donor registration rates as well as driver's license applications. METHODS:The purpose of this project was to describe the variability in the phrasing of the organ donor registration question by state bureaus of motor vehicles as well as other application questions that might influence this decision. In particular, the frequency of states employing empirically supported messages to increase donor registrations was ascertained. The content and phrasing of 46 different driver's license applications was coded in regard to seeking organ donor registrations. FINDINGS:No states used the empirically supported strategies of reciprocity, descriptive norms, or loss/gain framing from the interdisciplinary field of behavioral economics. Twelve states used injunctive norms to signify social approval for organ donation. Many state applications had lengthy organ donation sections and health questions that could discourage donor registrations. DISCUSSION:There is an extremely low use of empirically supported messages to increase organ donation registrations in driver's license applications in the United States. Opportunities exist for thoughtful consideration of the wording of driver's license applications. States interested in exploring ways to increase donations could undertake controlled variation of applications to test the effects of message framing on registration rates.

Background: The full-thickness resection device (FTRD)was recently introduced in the US and has made endoscopic resection of difficult lesions and those with deep wall origin/infiltration possible using non-exposure resection technique. Although initial studies were promising, outcome results of FTRD in the literature are scarce.
Aim(s): To study the feasibility, effciacy, and safety of FTRD for the resection of colonic lesions.
Method(s): Patients who underwent endoscopic full-thickness resection (EFTR)using the FTRD for lower GI lesions at 24 U.S. tertiary-care centers between 10/17 and 10/18 were included in this retrospective study. Outcomes were technical success (defined as en-block resection)and R0 histologic margin. Chi square test was used to assess the association between lesion type, size, and location with the two outcomes.
Result(s): A total of 79 patients (mean age 65 yr, 39.2% F)underwent resection of colonic lesions using the FTRD. The most common indication was difficult adenoma (defined as non-lifting, recurrent, residual or involving appendiceal orifice/diverticular opening)in 48 (60.8 %)patients, followed by adenocarcinoma in 17 (21.5%), and sub-epithelial lesions in 10 (12.7 %). Lesion location was in the proximal colon in 46 (58.2%)patients, followed by distal colon in 17 (21.5%), and rectum in 16 (20.3%). Mean pre-resection lesion diameter and total procedure time were 15.3 +/- 6.5 mm and 63 +/-32 min, respectively. Majority of patients underwent MAC sedation and received no prophylactic antibiotics. Most patients, 72.2%, were discharged post-procedurally. Technical success was achieved in 67 (84.8 %)patients. For the 12 patients with technical failure, 5 underwent hot snare resection, 2 endoscopic submucosal dissection, 1 was managed surgically, while 4 had no further interventions. R0 resection was achieved in 88.9% of patients. A total of 9 (11.4%)adverse events occurred. Mild, moderate, and severe AE had a frequency of 6 (7.6%), 1 (1.3%), and 2 (2.5%), respectively. Most common AE was FTRD mechanical failure in 5 cases (6.3%), with one leading to perforation requiring surgery (severe event). Bleeding was reported in 3 cases (3.8%), with one case requiring endoscopic intervention 2-days post-procedure. One patient, despite being on pre and post procedure antibiotics, developed appendicitis 10-days post-procedure and was managed surgically (severe event). Technical success and R0 resection were not significantly associated with lesion type, size, or location.
Conclusion(s): Results from this first U.S multicenter study suggest that EFTR is a feasible, safe, and effective technique for EFTR of difficult colonic lesions. Surgical management can be avoid in the vast majority of cases. Although adverse events are not uncommon, severe complications are rare. [Figure presented][Figure presented]
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It is unclear if impairments in social functioning and peer relationships significantly differ across common developmental conditions such as attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), conduct disorder (CD), and associated callous-unemotional traits (CU traits). The current study explored sex differences and symptoms of parent- and teacher-reported psychopathology on peer relationships and prosocial behaviour in a sample of 147 referred children and adolescents (aged 5-17 years; 120 m). The results showed that increases in parent-reported ADHD Inattentive symptoms and teacher-reported ADHD Hyperactive-Impulsive symptoms, CD, ODD, and CU traits were significantly associated with peer relationship problems across sex. At the same time, teacher-reported symptoms of ODD and both parent- and teacher-reported CU traits were related to difficulties with prosocial behaviour, for both boys and girls, with sex explaining additional variance. Overall, our findings show a differential association of the most common disruptive behaviours to deficits in peer relationships and prosocial behaviour. Moreover, they highlight that different perspectives of behaviour from parents and teachers should be taken into account when assessing social outcomes in disruptive behaviours. Given the questionable separation of conduct problem-related constructs, our findings not only point out the different contribution of those aspects in explaining peer relationships and prosocial behaviour, but furthermore the variance from different informants about those aspects of conduct problems.

Manual skills such as reaching, grasping, and exploring objects appear months earlier in infancy than locomotor skills such as walking. To what extent do infants incorporate an old skill (manual actions on objects) into the development of a new skill (walking)? We video recorded 64 sessions of infants during free play in a laboratory playroom. Infants' age (12.7-19.5 months), walking experience (0.5-10.3 months), and walking proficiency (speed, step length, etc.) varied widely. We found that the earlier developing skills of holding and exploring objects are immediately incorporated into the later developing skill of walking. Although holding incurred a reliable cost to infants' gait patterns, holding and exploring objects in hand were relatively common activities, and did not change with development. Moreover, holding objects was equally common in standing and walking. However, infants did not interact with objects indiscriminately: Object exploration was more frequent while standing than walking, and infants selectively chose lighter objects to carry and explore. Findings suggest that the earlier appearance of some skills may serve to motivate and enrich later appearing skills.

Background: In Western countries, most patients with early gastric cancer (EGC)are still being treated with gastrectomy. Endoscopic submucosal dissection (ESD)is a widely accepted treatment option for EGC in Asia and has become increasingly performed in the West. To date, outcomes data on gastric ESD in the Western settings have been limited to small, single-center studies, with a lack of data coming from North America.
Aim(s): To evaluate gastric ESD outcomes across various centers in North America.
Method(s): This was a retrospective analysis of prospectively collected data on consecutive patients with gastric epithelial neoplasia who underwent ESD between 1/2008 to 10/2018 at 19 centers. Primary end point was the rate of en bloc resection. Secondary outcomes included: (1)rate of complete (R0)and curative resection, (2)adverse event rates, and (3)rates of recurrence and gastric cancer-related death.
Result(s): Of 253 patients who were referred for gastric ESD, ESD was not technically feasible in 6 cases (1 due to deeply invasive cancer and 5 due to severe submucosal fibrosis from prior endoscopic resection). In 247 patients (mean age 69 yrs; 56% male; 50% Caucasian), including 143 (58%)adenomas, 67 (27%)EGC, and 28 (11%)neuroendocrine tumors (NET), ESD was attempted. Median procedure time was 90 min (IQR 55 - 124). In 38% of cases, ESD was performed in an outpatient setting. En-bloc resection rates for all lesions, EGCs, adenomas, and NETs were 92%, 94%, 89%, and 90%, respectively. R0 resection rates for all lesions, EGC, adenomas, and NET were 81%, 76%, 87%, and 70%, respectively. Curative resection according to Japanese criteria was achieved in 76% (16/21)of EGCs fulfilling the standard criteria and 69% (25/36)of EGCs fulfilling the expanded criteria. Intraprocedural perforation occurred in 8%(n=21). Of these, all but two cases were treated successfully with endoscopic therapy. Two cases (0.8%)required surgery due to perforation, and both occurred during the early phase of the learning curve. Delayed bleeding occurred in 8 cases (3%). No delayed perforation or procedure-related deaths were observed. In the EGC cohort, local recurrence was observed in 4 cases (11%)and all were following non-curative resection. In the gastric adenoma group, there were 5 (6.7%)local recurrences after ESD (1.8% after R0 resection vs 44% after non-R0 resection, p=0.001). After a median follow-up of about 12 months post-operatively, no metastatic recurrences or gastric cancer-related deaths were observed.
Conclusion(s): This large multicenter study demonstrated high rates of en bloc and R0 resections of gastric neoplasia in North America, comparable to that of Eastern centers. We recommend ESD as treatment of choice for gastric neoplasia including lesions fulfilling standard and expanded criteria for EGC. [Figure presented][Figure presented]
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In the last 15 years, there has been a marked increase in the number of available stimulant formulations with the emphasis on long-acting formulations, and the introduction of several novel delivery systems such as orally dissolving tablets, chewable tablets, extended-release liquid formulations, transdermal patches, and novel "beaded" technology. All of these formulations involve changes to the pharmaceutical delivery systems of the two existing compounds most commonly employed to treat attention-deficit/hyperactivity disorder (ADHD), amphetamine (AMP) and methylphenidate (MPH). In addition to these new formulations, our knowledge about the individual differences in response has advanced and contributes to a more nuanced approach to treatment. The clinician can now make increasingly informed choices about these formulations and more effectively individualize treatment in a way that had not been possible before. In the absence of reliable biomarkers that can predict individualized response to ADHD treatment, clinical knowledge about differences in MPH and AMP pharmacodynamics, pharmacokinetics, and metabolism can be utilized to personalize treatment and optimize response. Different properties of these new formulations (delivery modality, onset of action, duration of response, safety, and tolerability) will most likely weigh heavily into the clinician's choice of formulation. To manage the broad range of options that are now available, clinicians should familiarize themselves in each of these categories for both stimulant compounds. This review is meant to serve as an update and a guide to newer stimulant formulations and includes a brief review of ADHD and stimulant properties.

BACKGROUND:Caregivers of children with primary immunodeficiency disorders (PIDs) experience significant psychological distress during their child's hematopoietic cell transplantation (HCT) process. OBJECTIVES:This study aims to understand caregiver challenges and identify areas for health care system-level improvements to enhance caregiver well-being. METHODS:In this mixed-methods study caregivers of children with PIDs were contacted in August to November 2017 through online and electronic mailing lists of rare disease consortiums and foundations. Caregivers were invited to participate in an online survey assessing sociodemographic variables, the child's medical characteristics, psychosocial support use, and the World Health Organization-5 Well-Being Index. Open-ended questions about health care system improvements were included. Descriptive statistics and linear multivariate regression analyses were conducted. A modified content analysis method was used to code responses and identify emergent themes. RESULTS:Among the 80 caregiver respondents, caregivers had a median age of 34 years (range, 23-62 years) and were predominantly female, white, and married with male children given a diagnosis of severe combined immune deficiency. In the adjusted regression model lower caregiver well-being was significantly associated with lower household income and medical complications. Challenges during HCT include maintaining relationships with partners and the child's healthy sibling or siblings, managing self-care, and coping with feelings of uncertainty. Caregivers suggested several organizational-level solutions to enhance psychosocial support, including respite services, online connections to other PID caregivers, and bedside mental health services. CONCLUSIONS:Certain high-risk subpopulations of caregivers might need more targeted psychosocial support to reduce the long-term effect of the HCT experience on their well-being. Caregivers suggested several organizational-level solutions for provision of this support.

Identify correlates of nicotine dependence [lifetime (l) and ongoing (o)] in adults with attention-deficit/hyperactivity disorder (ADHD) in childhood. We conducted a 33-year prospective follow-up of boys (mean age 8) with combined type ADHD (n = 135/207, 65% original sample). Correlates of nicotine dependence in adulthood were selected from characteristics obtained in childhood and adolescence. Among selected childhood features, only immature behavior was significantly related to nicotine dependence (OR(o) = 0.29, p = 0.02), indexing decreased risk. In contrast, several adolescent variables significantly correlated (p < 0.01) with nicotine dependence at mean age 41, including alcohol substance use disorder (SUD, OR(l) = 4.97), non-alcohol SUD (OR(o) = 4.33/OR(l) = 10.93), parental antisocial personality disorder (OR(l) = 4.42), parental SUD (OR(l) = 3.58), dropped out of school (OR(l) = 2.29), impulsivity (OR(o) = 1.53/OR(l) = 1.59), hyperactivity (OR(o) = 1.38), and number of antisocial behaviors (OR(o) = 1.10/OR(l) = 1.14). Results highlight the role of adolescent psychopathology in the development of nicotine dependence, motivating prospective longitudinal efforts to better define the developmental trajectories of risk and protection.

Background: Factors associated with need for surgical intervention (SI)following endoscopic therapy for iatrogenic luminal perforations are not well known. We aim to identify predictors of need for SI amongst patients undergoing attempted endoscopic closure following iatrogenic luminal perforation.
Method(s): We conducted a retrospective review of iatrogenic perforations that underwent endoscopic closure attempts in 7 North American referral centers. Data was collected including patient demographics, index perforation procedure, attempted closure procedures and need for surgical repair. Univariate and multivariable logistic regression analyses were performed.
Result(s): A total of 144 iatrogenic perforation cases were reviewed. Only 22 patients (15.3%)required SI following endoscopic closure attempts. Perforations occurred after upper endoscopy (67), colonoscopy (35), surgical endoscopy (17), and ERCP (25)interventions as defined in Figure 1. Notably none of the surgical endoscopy cases required surgical intervention. The most common perforation locations included: duodenum (35; 24.3%), esophagus (32; 22.2%), colon (32; 22.2%), and stomach (20; 13.9%). Perforation was recognized during the index procedure in 128 patients (88.9%). Needle decompression was needed in 9 cases (6.3%). Twelve patients (8.3%)underwent more than one endoscopic closure session. Multiple endoscopic closure modalities were used in 24 cases (16.7%). Most common modalities used included: through-the-scope clips (TTS, 58; 40.3%), stents (42; 29.2%), over-the-scope clips (OTSC, 37; 25.7%), and endoscopic suturing (27; 18.8%). On univariate analysis, needle decompression was a significant predictor of need for SI (27.3% vs. 2.5%); while stent use (9.1% vs. 32.8%), technical (31.8% vs. 94.3%)and immediate clinical success (27.3% vs. 95.1%)were inversely associated (Table 1). On multivariable analysis, index colonoscopy-related perforation, needle decompression and need for multiple endoscopic closure modalities were significant predictors of need for SI; while use of TTS clips and immediate clinical success were inversely associated (Table 1). None of the other examined factors predicted the need for SI, outlined in Table 1.
Conclusion(s): The need for surgical intervention after attempted endoscopic closure of iatrogenic perforations is low. Needle decompression, index colonoscopy-related perforation, and use of multiple endoscopic closure modalities were predictors of need for surgical intervention. [Figure presented]Univariate and multivariable analyses of need for surgical intervention after attempted endoscopic closure of iatrogenic perforations
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Autofluorescence is the emission of light by naturally occurring tissue components on the absorption of incident light. Autofluorescence within the eye is associated with several disorders, such as Age-related Macular Degeneration (AMD) which is a leading cause of central vision loss. Its pathogenesis is incompletely understood, but endogenous fluorophores in retinal tissue might play a role. Hyperspectral fluorescence microscopy of ex-vivo retinal tissue can be used to determine the fluorescence emission spectra of these fluorophores. Comparisons of spectra in healthy and diseased tissues can provide important insights into the pathogenesis of AMD. However, the spectrum from each pixel of the hyperspectral image is a superposition of spectra from multiple overlapping tissue components. As spectra cannot be negative, there is a need for a non-negative blind source separation model to isolate individual spectra. We propose a tensor formulation by leveraging multiple excitation wavelengths to excite the tissue sample. Arranging images from different excitation wavelengths as a tensor, a non-negative tensor decomposition can be performed to recover a provably unique low-rank model with factors representing emission and excitation spectra of these materials and corresponding abundance maps of autofluorescent substances in the tissue sample. We iteratively impute missing values common in fluorescence measurements using Expectation-Maximization and use L₂ regularization to reduce ill-posedness. Further, we present a framework for performing group hypothesis testing on hyperspectral images, finding significant differences in spectra between AMD and control groups in the peripheral macula. In the absence of ground truth, i.e. molecular identification of fluorophores, we provide a rigorous validation of chosen methods on both synthetic and real images where fluorescence spectra are known. These methodologies can be applied to the study of other pathologies presenting autofluorescence that can be captured by hyperspectral imaging.