Faculty Bibliography

BACKGROUND:Belatacept may impair humoral immunity, impacting the effectiveness of SARS-CoV-2 mRNA vaccines in transplant recipients. We investigated immunogenicity after SARS-CoV-2 mRNA vaccines in kidney transplant recipients who are and are not taking belatacept. METHODS:Participants were recruited between December 9, 2020, and April 1, 2021. Blood samples were collected after dose 1 and dose 2 (D1, D2) and analyzed using either an anti-SARS-CoV-2 enzyme immunoassay against the S1 domain of the SARS-CoV-2 spike protein or immunoassay against the receptor-binding domain of the SARS-CoV-2 spike protein. Stabilized inverse probability of treatment weights was used to compare immunogenicity, and a weighted logistics regression was used to calculate fold change of positive response. RESULTS:Among the 609 participants studied, 24 (4%) were taking belatacept. After dose 1, 0/24 (0%) belatacept patients had detectable antibodies, compared with 77 of 568 (14%) among the equivalent nonbelatacept population (P = 0.06). After dose 2, 1/19 (5%) belatacept patients had detectable antibodies, compared with 190/381 (50%) among the equivalent nonbelatacept population (P < 0.001). Belatacept use was associated with 16.7-fold lower odds of having a positive post-D2 titer result (P < 0.01). CONCLUSIONS:Additional measures need to be explored to protect kidney transplant recipients taking belatacept. Best safety practices should be continued despite vaccination among this population.

BACKGROUND:With stressors of dialysis prekidney transplantation (KT) and restoration of kidney function post-KT, it is likely that KT recipients experience a decline in functional status while on the waitlist and improvements post-KT. METHODS:We leveraged 224 832 KT recipients from the national registry (SRTR, February 1990-May 2019) with measured Karnofsky Performance Status (KPS, 0%-100%) at listing, KT admission, and post-KT. We quantified the change in KPS from listing to KT using generalized linear models. We described post-KT KPS trajectories using adjusted mixed-effects models and tested whether those trajectories differed by age, sex, race, and diabetes status using a Wald test among all KT recipients. We then quantified risk adverse post-KT outcomes (mortality and all-cause graft loss [ACGL]) by preoperative KPS and time-varying KPS. RESULTS:Mean KPS declined from listing (83.7%) to admission (78.9%) (mean = 4.76%, 95% confidence interval [CI]: -4.82, -4.70). After adjustment, mean KPS improved post-KT (slope = 0.89%/y, 95% CI: 0.87, 0.91); younger, female, non-Black, and diabetic recipients experienced greater post-KT improvements (Pinteractions < 0.001). Lower KPS (per 10% decrease) at admission was associated with greater mortality (adjusted hazard ratio [aHR] = 1.11, 95% CI: 1.10, 1.11) and ACGL (aHR = 1.08, 95% CI: 1.08, 1.09) risk. Lower post-KT KPS (per 10% decrease; time-varying) were more strongly associated with mortality (aHR = 1.93, 95% CI: 1.92, 1.94) and ACGL (aHR = 1.84, 95% CI: 1.83, 1.85). CONCLUSIONS:Functional status declines pre-KT and improves post-KT in the national registry. Despite post-KT improvements, poorer functional status at KT and post-KT are associated with greater mortality and ACGL risk. Because of its dynamic nature, clinicians should repeatedly screen for lower functional status pre-KT to refer vulnerable patients to prehabilitation in hopes of reducing risk of adverse post-KT outcomes.

BACKGROUND:The novel coronavirus 2019 (COVID-19) pandemic has transformed health care. With the need to limit COVID-19 exposures, telemedicine has become an increasingly important format for clinical care. Compared with other fields, neuro-ophthalmology faces unique challenges, given its dependence on physical examination signs that are difficult to elicit outside the office setting. As such, it is imperative to understand both patient and provider experiences to continue to adapt the technology and tailor its application. The purpose of this study is to analyze both neuro-ophthalmology physician and patient satisfaction with virtual health visits during the time of the COVID-19 pandemic. METHODS:Across three institutions (NYU Langone Health, Indiana University Health, and Columbia University Medical Center), telemedicine surveys were administered to 159 patients. Neuro-ophthalmologists completed 157 surveys; each of these were linked to a single patient visit. Patient surveys consisted of 5 questions regarding visit preparation, satisfaction, challenges, and comfort. The physician survey included 4 questions that focused on ability to gather specific clinical information by history and examination. RESULTS:Among 159 patients, 104 (65.4%) reported that they were satisfied with the visit, and 149 (93.7%) indicated that they were comfortable asking questions. Sixty-eight (73.9%) patients found the instructions provided before the visit easy to understand. Potential areas for improvement noted by patients included more detailed preparation instructions and better technology (phone positioning, Internet connection, and software). More than 87% (137/157) of neuro-ophthalmologists surveyed reported having performed an examination that provided enough information for medical decision-making. Some areas of the neuro-ophthalmologic examination were reported to be easy to conduct (range of eye movements, visual acuity, Amsler grids, Ishihara color plates, and pupillary examination). Other components were more difficult (saccades, red desaturation, visual fields, convergence, oscillations, ocular alignment, and smooth pursuit); some were especially challenging (vestibulo-ocular reflex [VOR], VOR suppression, and optokinetic nystagmus). Clinicians noted that virtual health visits were limited by patient preparation, inability to perform certain parts of the examination (funduscopy and pupils), and technological issues. CONCLUSIONS:Among virtual neuro-ophthalmology visits evaluated, most offer patients with appointments that satisfy their needs. Most physicians in this cohort obtained adequate clinical information for decision-making. Even better technology and instructions may help improve aspects of virtual health visits.

IMPORTANCE:The National Pediatric Readiness Project is a US initiative to improve emergency department (ED) readiness to care for acutely ill and injured children. However, it is unclear whether high ED pediatric readiness is associated with improved survival in US trauma centers. OBJECTIVE:To evaluate the association between ED pediatric readiness, in-hospital mortality, and in-hospital complications among injured children presenting to US trauma centers. DESIGN, SETTING, AND PARTICIPANTS:A retrospective cohort study of 832 EDs in US trauma centers in 50 states and the District of Columbia was conducted using data from January 1, 2012, through December 31, 2017. Injured children younger than 18 years who were admitted, transferred, or with injury-related death in a participating trauma center were included in the analysis. Subgroups included children with an Injury Severity Score (ISS) of 16 or above, indicating overall seriously injured (accounting for all injuries); any Abbreviated Injury Scale (AIS) score of 3 or above, indicating at least 1 serious injury; a head AIS score of 3 or above, indicating serious brain injury; and need for early use of critical resources. EXPOSURES:Emergency department pediatric readiness for the initial ED visit, measured through the weighted Pediatric Readiness Score (range, 0-100) from the 2013 National Pediatric Readiness Project ED pediatric readiness assessment. MAIN OUTCOMES AND MEASURES:In-hospital mortality, with a secondary composite outcome of in-hospital mortality or complication. For the primary measurement tools used, the possible range of the AIS is 0 to 6, with 3 or higher indicating a serious injury; the possible range of the ISS is 0 to 75, with 16 or higher indicating serious overall injury. The weighted Pediatric Readiness Score examines and scores 6 domains; in this study, the lowest quartile included scores of 29 to 62 and the highest quartile included scores of 93 to 100. RESULTS:There were 372 004 injured children (239 273 [64.3%] boys; median age, 10 years [interquartile range, 4-15 years]), including 5700 (1.5%) who died in-hospital and 5018 (1.3%) who developed in-hospital complications. Subgroups included 50 440 children (13.6%) with an ISS of 16 or higher, 124 507 (33.5%) with any AIS score of 3 or higher, 57 368 (15.4%) with a head AIS score of 3 or higher, and 32 671 (8.8%) requiring early use of critical resources. Compared with EDs in the lowest weighted Pediatric Readiness Score quartile, children cared for in the highest ED quartile had lower in-hospital mortality (adjusted odds ratio [aOR], 0.58; 95% CI, 0.45-0.75), but not fewer complications (aOR for the composite outcome 0.88; 95% CI, 0.74-1.04). These findings were consistent across subgroups, strata, and multiple sensitivity analyses. If all children cared for in the lowest-readiness quartiles (1-3) were treated in an ED in the highest quartile of readiness, an additional 126 lives (95% CI, 97-154 lives) might be saved each year in these trauma centers. CONCLUSIONS AND RELEVANCE:In this cohort study, injured children treated in high-readiness EDs had lower mortality compared with similar children in low-readiness EDs, but not fewer complications. These findings support national efforts to increase ED pediatric readiness in US trauma centers that care for children.

Importance:Early evidence shows a decrease in the number of US births during the COVID-19 pandemic, yet few studies have examined individual-level factors associated with pregnancy intention changes, especially among diverse study populations or in areas highly affected by COVID-19 in the US. Objective:To study changes in pregnancy intention following the outbreak of the COVID-19 pandemic and identify factors possibly associated with these changes. Design, Setting, and Participants:A cross-sectional, population-based study was conducted among women who were currently pregnant or had delivered a live infant and responded to a survey emailed to 2603 women (n = 1560). Women who were mothers of young children enrolled in the prospective New York University Children's Health and Environment Study birth cohort were included; women who were not currently pregnant or recently postpartum were excluded. Exposures:Demographic, COVID-19-related, stress-related, and financial/occupational factors were assessed via a survey administered from April 20 to August 31, 2020. Main Outcomes and Measures:Pregnancy intentions before the COVID-19 pandemic and change in pregnancy intentions following the outbreak. Results:Of the 2603 women who were sent the survey, 1560 (59.9%) who were currently pregnant or had delivered a live infant responded, and 1179 women (75.6%) answered the pregnancy intention questions. Mean (SD) age was 32.2 (5.6) years. Following the outbreak, 30 of 61 (49.2%) women who had been actively trying to become pregnant had ceased trying, 71 of 191 (37.2%) women who had been planning to become pregnant were no longer planning, and 42 of 927 (4.5%) women who were neither planning nor trying were newly considering pregnancy. Among those who ceased trying, fewer than half (13 [43.3%]) thought they would resume after the pandemic. Of those pre-COVID-19 planners/triers who stopped considering or attempting pregnancy, a greater proportion had lower educational levels, although the difference was not statistically significant on multivariable analysis (odds ratio [OR], 2.14; 95% CI, 0.92-4.96). The same was true for those with higher stress levels (OR, 1.09; 95% CI, 0.99-1.20) and those with greater financial insecurity (OR, 1.37; 95% CI, 0.97-1.92. Those who stopped considering or attempting pregnancy were more likely to respond to the questionnaire during the peak of the outbreak (OR, 2.04; 95% CI, 1.01-4.11). Of those pre-COVID-19 nonplanners/nontriers who reported newly thinking about becoming pregnant, a smaller proportion responded during the peak, although the finding was not statistically significant on multivariable analysis (OR, 0.52; 95% CI, 0.26-1.03). Likewise, fewer respondents who were financially insecure reported newly considering pregnancy, although the finding was not statistically significant (OR, 0.69; 95% CI, 0.46-1.03). They were significantly less likely to be of Hispanic ethnicity (OR, 0.27; 955 CI, 0.10-0.71) and more likely to have fewer children in the home (OR, 0.62; 95% CI, 0.40-0.98) or self-report a COVID-19 diagnosis (OR, 2.70; 95% CI, 1.31-5.55). Conclusions and Relevance:In this cross-sectional study of 1179 women who were mothers of young children in New York City, increased stress and financial insecurity owing to the COVID-19 pandemic paralleled a reduction in pregnancy intention in the early months of the pandemic, potentially exacerbating long-term decreases in the fertility rate.

BACKGROUND:Prolactin is synthesized in the ovaries and may play a role in ovarian cancer etiology. One prior prospective study observed a suggestive positive association between prolactin levels and risk of ovarian cancer. METHODS:We conducted a pooled case-control study of 703 cases and 864 matched controls nested within five prospective cohorts. We used unconditional logistic regression to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI) for the association between prolactin and ovarian cancer risk. We examined heterogeneity by menopausal status at blood collection, body mass index (BMI), age, and histotype. RESULTS:Among women with known menopausal status, we observed a positive trend in the association between prolactin and ovarian cancer risk (ptrend=0.045; OR, quartile 4 vs. 1=1.34; 95% CI=0.97-1.85), but no significant association was observed for premenopausal or postmenopausal women individually (corresponding OR=1.38; 95%CI=0.74-2.58; ptrend=0.32 and OR=1.41; 95% CI=0.93-2.13; ptrend=0.08, respectively; pheterogeneity=0.91). In stratified analyses, we observed a positive association between prolactin and risk for women with BMI {greater than or equal to}25 kg/m2, but not BMI <25 kg/m2 (corresponding OR=2.68; 95% CI=1.56-4.59; ptrend<0.01 and OR=0.90; 95% CI=0.58-1.40; ptrend=0.98, respectively; pheterogeneity<0.01). Associations did not vary by age, postmenopausal hormone therapy use, histotype, or time between blood draw and diagnosis. CONCLUSIONS:We found a trend between higher prolactin levels and increased ovarian cancer risk, especially among women with a BMI >=25 kg/m2. IMPACT/CONCLUSIONS:This work supports a previous study linking higher prolactin with ovarian carcinogenesis in a high adiposity setting. Future work is needed to understand the mechanism underlying this association.

Active-duty Army personnel can be exposed to traumatic warzone events and are at increased risk for developing post-traumatic stress disorder (PTSD) compared with the general population. PTSD is associated with high individual and societal costs, but identification of predictive markers to determine deployment readiness and risk mitigation strategies is not well understood. This prospective longitudinal naturalistic cohort study-the Fort Campbell Cohort study-examined the value of using a large multidimensional dataset collected from soldiers prior to deployment to Afghanistan for predicting post-deployment PTSD status. The dataset consisted of polygenic, epigenetic, metabolomic, endocrine, inflammatory and routine clinical lab markers, computerized neurocognitive testing, and symptom self-reports. The analysis was computed on active-duty Army personnel (N = 473) of the 101st Airborne at Fort Campbell, Kentucky. Machine-learning models predicted provisional PTSD diagnosis 90-180 days post deployment (random forest: AUC = 0.78, 95% CI = 0.67-0.89, sensitivity = 0.78, specificity = 0.71; SVM: AUC = 0.88, 95% CI = 0.78-0.98, sensitivity = 0.89, specificity = 0.79) and longitudinal PTSD symptom trajectories identified with latent growth mixture modeling (random forest: AUC = 0.85, 95% CI = 0.75-0.96, sensitivity = 0.88, specificity = 0.69; SVM: AUC = 0.87, 95% CI = 0.79-0.96, sensitivity = 0.80, specificity = 0.85). Among the highest-ranked predictive features were pre-deployment sleep quality, anxiety, depression, sustained attention, and cognitive flexibility. Blood-based biomarkers including metabolites, epigenomic, immune, inflammatory, and liver function markers complemented the most important predictors. The clinical prediction of post-deployment symptom trajectories and provisional PTSD diagnosis based on pre-deployment data achieved high discriminatory power. The predictive models may be used to determine deployment readiness and to determine novel pre-deployment interventions to mitigate the risk for deployment-related PTSD.

OBJECTIVE:To assess current practice patterns with respect to protocols used for incidental pancreatic cyst follow-up, management guidelines, and template reporting. METHODS:The Society of Abdominal Radiology Disease Focused Panel on intraductal pancreatic neoplasms distributed an anonymous 14-question survey to its members in June 2018 that focused on current utilization of incidental pancreatic cyst guidelines, protocols, and template reporting. RESULTS:Among the 1,390 e-mail invitations, 323 responded and 94.7% (306 of 323) completed all questions. Respondents were mainly radiologists (93.8%, 303 of 323) from academic institutions (74.7%, 227 of 304) in North America (93.7%, 286 of 305). Of respondents, 42.5% (136 of 320) preferred 2017 ACR recommendations, 17.8% (57 of 320) homegrown systems, 15.0% (48 of 320) Fukuoka guidelines, and 7.8% (25 of 320) American Gastroenterological Association guidelines. The majority (68.7%, 222 of 323) agreed or strongly agreed that developing a single international consensus recommendation for management was important, and most radiologists preferred to include them in reports (231 of 322, 71.7%); yet only half included recommendations in >75% of reports (161 of 321). Magnetic resonance cholangiopancreatography was the modality of choice for follow-up of <2.5 cm cysts. Intravenous contrast was routinely used by 69.7% (212 of 304). Standardized reporting templates were rarely used in practice (12.8% 39 of 306). CONCLUSIONS:Nearly 7 of 10 radiologists desire a unified international consensus recommendation for management of incidental cystic pancreatic lesions; ACR 2017 recommendations are most commonly used, followed by homegrown systems and Fukuoka guidelines. The majority of radiologists routinely use magnetic resonance cholangiopancreatography with intravenous contrast for follow-up of incidental cystic lesions, but template reporting is rarely used.

Physical activity and social support are associated with better outcomes after surviving acute myocardial infarction (AMI), and greater walkability has been associated with activity and support. We used data from the SILVER-AMI study (November 2014-June 2017), a longitudinal cohort of community-living adults ≥ 75 years hospitalized for AMI to assess associations of neighborhood walkability with health outcomes, and to assess whether physical activity and social support mediate this relationship, if it exists. We included data from 1345 participants who were not bedbound, were discharged home, and for whom we successfully linked walkability scores (from Walk Score®) for their home census block. Our primary outcome was hospital-free survival time (HFST) at six months after discharge; secondary outcomes included physical and mental health at six months, assessed using SF-12. Physical activity and social support were measured at baseline. Covariates included cognition, functioning, comorbidities, participation in rehabilitation or physical therapy, and demographics. We employed survival analysis to examine associations between walkability and HFST, before and after adjustment for covariates; we repeated analyses using linear regression with physical and mental health as outcomes. In adjusted models, walkability was not associated with physical health (ß = 0.010; 95% CI: -0.027, 0.047), mental health (ß = -0.08; 95% CI: -0.175, -0.013), or HFST (ß = 0.008; 95% CI: -0.023, 0.009). Social support was associated with mental health in adjusted models. Neighborhood walkability was not predictive of outcomes among older adults with existing coronary disease, suggesting that among older adults, mobility limitations may supercede neighborhood walkability.