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Pulmonary antibody-mediated rejection (AMR) consensus criteria categorize AMR by diagnostic certainty. This study aims to define the clinical features and associated outcomes of these recently defined AMR categories.Adjudication committees reviewed clinical data of 335 lung transplant recipients to define clinical or subclinical AMR based on the presence of allograft dysfunction, and the primary endpoints, time from transplant to allograft failure, a composite endpoint of chronic lung allograft dysfunction and/or death. Clinical AMR was subcategorized based on diagnostic certainty as definite, probable or possible AMR if 4, 3, or 2 characteristic features were present, respectively. Allograft injury was assessed via plasma donor-derived cell-free DNA (ddcfDNA). Risk of allograft failure and allograft injury was compared for AMR categories using regression models.Over the 38.5 months follow-up, 28.7% of subjects developed clinical AMR (n = 96), 18.5% developed subclinical AMR (n = 62) or 58.3% were no AMR (n = 177). Clinical AMR showed higher risk of allograft failure and ddcfDNA levels compared to subclinical or no AMR. Clinical AMR included definite/probable (n = 21) or possible AMR (n = 75). These subcategories showed similar clinical characteristics, ddcfDNA levels, and risk of allograft failure. However, definite/probable AMR showed greater measures of AMR severity, including degree of allograft dysfunction and risk of death compared to possible AMR.Clinical AMR showed greater risk of allograft failure than subclinical AMR or no AMR. Subcategorization of clinical AMR based on diagnostic certainty correlated with AMR severity and risk of death, but not with the risk of allograft failure.

Many lung transplants fail due to chronic lung allograft dysfunction (CLAD). We recently showed that transbronchial biopsies (TBBs) from CLAD patients manifest severe parenchymal injury and dedifferentiation, distinct from time-dependent changes. The present study explored time-selective and CLAD-selective transcripts in mucosal biopsies from the third bronchial bifurcation (3BMBs), compared to those in TBBs.We used genome-wide microarray measurements in 324 3BMBs to identify CLAD-selective changes as well as time-dependent changes and develop a CLAD classifier. CLAD-selective transcripts were identified with linear models for microarray data (limma) and were used to build an ensemble of 12 classifiers to predict CLAD. Hazard models and random forests were then used to predict the risk of graft loss using the CLAD classifier, transcript sets associated with rejection, injury, and time.T cell-mediated rejection and donor-specific antibody were increased in CLAD 3BMBs but most had no rejection. Like TBBs, 3BMBs showed a time-dependent increase in transcripts expressed in inflammatory cells that was not associated with CLAD or survival. Also like TBBs, the CLAD-selective transcripts in 3BMBs reflected severe parenchymal injury and dedifferentiation, not inflammation or rejection. While 3BMBs and TBBs did not overlap in their top 20 CLAD-selective transcripts, many CLAD-selective transcripts were significantly increased in both for example LOXL1, an enzyme controlling matrix remodeling. In Cox models for one-year survival, the 3BMB CLAD-selective transcripts and CLAD classifier predicted graft loss and correlated with CLAD stage. Many 3BMB CLAD-selective transcripts were also increased by injury in kidney transplants and correlated with decreased kidney survival, including LOXL1.Mucosal and transbronchial biopsies from CLAD patients reveal a diffuse molecular injury and dedifferentiation state that impacts prognosis and correlates with the physiologic disturbances. CLAD state in lung transplants shares features with failing kidney transplants, indicating elements shared by the injury responses of distressed organs.

Transplanted lungs suffer worse outcomes than other organ transplants with many developing chronic lung allograft dysfunction (CLAD), diagnosed by physiologic changes. Histology of transbronchial biopsies (TBB) yields little insight, and the molecular basis of CLAD is not defined. We hypothesized that gene expression in TBBs would reveal the nature of CLAD and distinguish CLAD from changes due simply to time posttransplant. Whole-genome mRNA profiling was performed with microarrays in 498 prospectively collected TBBs from the INTERLUNG study, 90 diagnosed as CLAD. Time was associated with increased expression of inflammation genes e.g. CD1E and immunoglobulins. After correcting for time, CLAD manifested not as inflammation but as parenchymal response-to-wounding, with increased expression of genes such as HIF1A, SERPINE2, and IGF1 that are increased in many injury and disease states and cancers, associated with development, angiogenesis, and epithelial response-to-wounding in pathway analysis. Fibrillar collagen genes were increased in CLAD, indicating matrix changes, and normal transcripts were decreased - dedifferentiation. Gene-based classifiers predicted CLAD with AUC 0.70 (no time-correction) and 0.87 (time-corrected). CLAD related gene sets and classifiers were strongly prognostic for graft failure and correlated with CLAD stage. Thus, in TBBs molecular changes indicate that CLAD primarily reflects severe parenchymal injury-induced changes and dedifferentiation.

Background Prior studies demonstrate that donor-derived cell-free DNA (dd-cfDNA) in lung transplant recipients may serve as a marker of allograft injury for detecting allograft rejection and infection. Clinical interpretation of dd-cfDNA requires understanding its biological variation in stable lung transplant patients in order to identify abnormal results suggesting underlying allograft dysfunction. This study establishes the biological variation and reference change values (RCV) of dd-cfDNA in stable lung transplant recipients using an analytically validated assay with an established analytic coefficient of variation (CVA). Methods The AlloSure® assay, a targeted, sequencing-based approach, was used to measure plasma dd-cfDNA in a cohort of lung transplant patients at 4 centers that used dd-cfDNA to monitor for allograft dysfunction in preference to surveillance transbronchial biopsy. Patients with stable allograft function and ≥3 dd-cfDNA samples were included. Intraindividual coefficient of variation (CVI), interindividual CV (CVG), index of individuality (II) and the RCV were calculated. Results Thirty-five patients with a combined 124 dd-cfDNA samples were included in the final analysis. The median dd-cfDNA was 0.31% (interquartile range 0.18%-0.68%), the 97.5th percentile and 95th percentile were 1.3% and 1.0%, respectively. In 30 stable patients with an average of 3.7 tests, the CVI was 25%, CVG 53%, II 0.47, and RCV 70%. Conclusion In stable lung transplant patients, fluctuations in dd-cfDNA levels of up to 70% or levels less than 1% are within normal biological variation. With further validation, these thresholds may be incorporated into surveillance monitoring algorithms to identify potentially abnormal results indicating allograft dysfunction.

Background: Older adults with mild cognitive impairment (MCI) receive fewer guideline-concordant treatments for multiple health conditions than those with normal cognition. Reasons for this disparity are unclear. Objective: To better understand this disparity, we describe physician understanding and experience with patient MCI, particularly physician identification of MCI, ability to distinguish between MCI and dementia, and perspectives on education and training in MCI and dementia. Methods: As part of a mixed-methods study assessing the influence of patient MCI on physician recommendations for acute myocardial infraction and stroke treatments, we conducted a descriptive qualitative study using semi-structured interviews of physicians from three specialties. Key question topics included participants’ identification of MCI, impressions of MCI and dementia awareness within their practice specialty, and perspectives on training and education in MCI. Results: The study included 22 physicians (8 cardiologists, 7 neurologists, and 7 internists). We identified two primary themes: There is 1) a lack of adequate understanding of the distinction between MCI and dementia; and 2) variation in physician approaches to identifying whether an older adult has MCI. Conclusion: These findings suggest that physicians have a poor understanding of MCI. Our results suggest that interventions that improve physician knowledge of MCI are needed.

Antimicrobial stewardship programs (ASPs) have made immense strides in optimizing antibiotic, antifungal, and antiviral use in clinical settings. However, although ASPs are required institutionally by regulatory agencies in the United States and Canada, they are not mandated for transplant centers or programs specifically. Despite the fact that solid organ transplant recipients in particular are at increased risk of infections from multidrug-resistant organisms, due to host and donor factors and immunosuppressive therapy, there currently are little rigorous data regarding stewardship practices in solid organ transplant populations, and thus, no transplant-specific requirements currently exist. Further complicating matters, transplant patients have a wide range of variability regarding their susceptibility to infection, as factors such as surgery of transplant, intensity of immunosuppression, and presence of drains or catheters in situ may modify the risk of infection. As such, it is not feasible to have a “one-size-fits-all” style of stewardship for this patient population. The objective of this white paper is to identify opportunities, risk factors, and ASP strategies that should be assessed with solid organ transplant recipients to optimize antimicrobial use, while producing an overall improvement in patient outcomes. We hope it may serve as a springboard for development of future guidance and identification of research opportunities.

Introduction Limited evidence exists on the effect of isavuconazonium sulfate and posaconazole delayed release tablets on tacrolimus dose-to-concentration ratios in lung transplant recipients. Project Aims The purpose of this evaluation was to assess the impact of novel triazoles on tacrolimus dose-to-concentration ratios. Design This retrospective review included lung transplant recipient ≥18 years of age from January 1, 2017 to October 1, 2020 who received either posaconazole delayed release tablets or isavuconazonium sulfate for. A paired analysis evaluated outcomes pre-triazole and post-triazole initiation. Results Forty-one patients met evaluation criteria for inclusion. A total of 34 of 41 patients received posaconazole delayed release tablets. Of these patients, 22 of 34 were transitioned from previous triazole to posaconazole delayed release tablets and experienced a 47% reduction in tacrolimus dose-to-concentration ratio. Twelve patients were newly initiated on posaconazole delayed release tablets and experienced a 50% reduction in tacrolimus dose-to-concentration ratios. Although not statistically significant, a 30% reduction in tacrolimus dose-to-concentration ratio was observed when transitioning to isavuconazonium sulfate from previous triazole therapy. Conclusion Limited data exists to provide guidance on tacrolimus dose adjustments with initiation and conversion of novel triazoles, however, this evaluation provides more knowledge on the drug interaction with novel triazoles and tacrolimus.

Patients with connective tissue disease (CTD) present unique surgical, perioperative, operative, and postoperative challenges related to the often underlying severe pulmonary hypertension and right ventricular dysfunction. The International Society for Heart and Lung Transplantation-supported consensus document on lung transplantation in patients with CTD standardization addresses the surgical challenges and relevant cardiac involvement in the perioperative, operative, and postoperative management in patients with CTD.

To describe the sonographic findings of endometrial intraepithelial neoplasia (EIN), a precursor of endometrial cancer.Cases were found by word search of pathology database 1/2013 to 6/2019. One hundred and seventy-eight patients with ultrasound1 year prior to biopsy were included. Medical records were searched for patient data. Two radiologists blindly classified images. Differences of opinion were decided by clinical report. Univariate and multivariate analyses were performed.Median time between ultrasound and first sampling procedure was 49 days. Median age was 55 (range 28-85) years. Endometrial thickness ranged from 2 to 90 mm. Mean endometrial thickness was 13 ± 6 mm in the noncancer group and 16 ± 11 mm in the cancer group (P = .02). The endometrium was almost always heterogeneous 175/178 (98%). Cysts were almost always multiple (89/109, 82%) and1 mm (72/109, 66%). Masses were most often5 mm (56/105, 55%) and ill-defined (41/105, 39%). Vascularity was present in 93/178 examinations (52%) and always associated with cysts and/or mass. There were 92 cancers, 25 with invasion (including 4 with tumor extension into adenomyosis). In 47 cases, the endometrial-myometrial interface was graded as ill-defined, 39 of whom had hysterectomy. There was macroscopic cancer in 11, microscopic cancer in 4, and invasive carcinoma in 12 patients (P for invasive cancer versus other outcomes = .02). Depth of invasion was 5-95%, with 6 cancers50%. Multivariate analysis showed thickness, polyps, and type of bleeding as the best set of independent variables for cancer (area under the receiver operating characteristic (ROC) curve [AUC] = .75). Replacing type of bleeding with age or menopausal status had AUC of .73 and .74, respectively.EIN has a variety of sonographic appearances with thickened endometrium with cysts and masses being common. Ill-definition of the endometrial-myometrial interface is a poor prognostic finding when seen in the absence of adenomyosis.

Background: Meta-analyses of individuals’ cognitive data are increasing to investigate the biomedical, lifestyle, and sociocultural factors that influence cognitive decline and dementia risk. Pre-statistical harmonization of cognitive instruments is a critical methodological step for accurate cognitive data harmonization, yet specific approaches for this process are unclear. Objective: To describe pre-statistical harmonization of cognitive instruments for an individual-level meta-analysis in the blood pressure and cognition (BP COG) study. Methods: We identified cognitive instruments from six cohorts (the Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, Coronary Artery Risk Development in Young Adults study, Framingham Offspring Study, Multi-Ethnic Study of Atherosclerosis, and Northern Manhattan Study) and conducted an extensive review of each item’s administration and scoring procedures, and score distributions. Results: We included 153 cognitive instrument items from 34 instruments across the six cohorts. Of these items, 42%were common across ≥2 cohorts. 86%of common items showed differences across cohorts. We found administration, scoring, and coding differences for seemingly equivalent items. These differences corresponded to variability across cohorts in score distributions and ranges. We performed data augmentation to adjust for differences. Conclusion: Cross-cohort administration, scoring, and procedural differences for cognitive instruments are frequent and need to be assessed to address potential impact on meta-analyses and cognitive data interpretation. Detecting and accounting for these differences is critical for accurate attributions of cognitive health across cohort studies.

Objectives: We compared the concurrent validity of the Montreal Cognitive Assessment (MoCA) with other cognitive screening instruments among Mexican Americans (MA) and non-Hispanic whites (NHW). Methods: In a community-based study in Nueces county, Texas (5/2/18-2/26/20), participants 65+ with MoCA ≤25 completed the Harmonized Cognitive Assessment Protocol. Regressions examined associations between MoCA and: 1) Mini Mental State Examination (MMSE); 2) abbreviated Community Screening Interview for Dementia (CSI-D); 3) Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Results: MA (n = 229) and NHW (n = 81) differed by education but not age or sex. MoCA and cognitive performance associations (MMSE, CSI-D-Respondent) did not differ between MA and NHW (p’s > .16). MoCA and informant rating associations (IQCODE, CSI-D-Informant) were stronger in NHW than MA (NHW R2 = 0.39 and 0.38, respectively; MA R2 = 0.30 and 0.28, respectively). Discussion: Our findings suggest non-equivalence across cognitive screening instruments among MAs and NHWs.

Background and Purpose: We determined the association between hospital factors, performance on transient ischemic attack (TIA) process measures, and 90-day ischemic stroke incidence. Methods: Longitudinal analysis of retrospectively obtained data on 9168 veterans ≥18 years with TIA presenting to the emergency department or inpatient unit at 69 Veterans Affairs hospitals with ≥10 eligible patients per year in fiscal years 2015 to 2018. Process measures were high/moderate potency statin within 7 days of discharge, antithrombotic by day 2, and hypertension control ( Results: During the 4-year study period, hospitals significantly increased statin use (adjusted odds ratio [aOR] per 1-year increase, 1.24 [95% CI, 1.17–1.32]; P P =0.44) nor antithrombotic use ( P =0.82) improved over time. Hospitals that admitted a higher proportion of TIA patients versus emergency department discharge had significantly greater use of statins (aOR per 10-percentage point increase in the proportion of TIA patients admitted, 1.09 [1.03–1.16]; P =0.003) and antithrombotics (aOR per 10-percentage point increase in TIA patients admitted, 1.14 [1.06–1.23]; P P =0.008 and aOR per 10-patient decrease in volume, 1.09 [1.01–1.16]; P =0.02). Higher emergency physician staffing was associated with lower 90-day stroke incidence (aOR per 1 full-time physician increase, 0.96 [0.92–0.99]; P =0.02) but other hospital factors were not. Conclusions: Hospitals admitting higher percentages of TIA patients and having higher emergency physician staffing have greater performance on select guideline-concordant process measures for TIA. Higher emergency physician staffing was associated with improved outcomes 90 days after TIA.

Mexican Americans (MA) are more likely to have cognitive impairment and dementia (CID), be diagnosed at an earlier age and live with CID longer, compared to non-Hispanic Whites (NHW). While studies have examined unmet needs of individuals with CID and their caregivers, few have focused on MA populations in the U.S. This paper examines the needs of community-residing individuals with CID and their caregivers in Nueces County, Texas, a county with one of the largest MA populations in the U.S., while exploring ethnic differences in needs identified.Using concept mapping, a mixed-method approach, qualitative input on perceived needs by informal caregivers and health professionals was collected. Participants then sorted and rated perceived needs. Using this information, multidimensional scaling and cluster analyses were conducted to map the relationship between perceived needs and determine their importance and priority.Five clusters were derived for caregivers and four for the health professionals. Themes across both caregivers and health professionals highlighted the need for specialized and team-based medical care, caregiver support and training, along with socio-economic and physical needs that help with day-to-day care of individuals with CID. Among caregivers, MA rated financial resources as more important and of higher priority compared to NHW. The health professionals' perspectives were aligned with those of all caregivers.By understanding the needs of caregivers and individuals with CID, we can help families deal with this disease and let caregivers thrive. This is especially important for minority populations like MAs.

Since the beginning of the lesbian, gay, bisexual, transgender, and queer (LGBTQ) rights movement, LGBTQ community centers have been on the front lines of mental health care for sexual and gender minorities (SGMs) across the United States. However, little is known about what types of mental health services LGBTQ community centers currently offer and their anticipated future needs, including training in and delivery of evidence-based practice.Sixty executive directors and chief executive officers of LGBTQ community centers across the United States completed a survey regarding their centers' current treatment capacity, format, and type as well as perceived future needs. Survey items were supplemented with qualitative questions about perceived barriers to and facilitators of strengthening the capacity of mental health services.Center directors perceived a high need for mental health care in their communities and strove to meet that need despite constrained resources. About half of the centers (52%) reported having fewer than five mental health staff; still, most reported providing support groups (98%) and individual psychotherapy (85%). Most centers (88%) reported providing general evidence-based care, such as cognitive-behavioral therapy (62%), and all reported high support for their staff to receive training in more specific types of evidence-based, LGBTQ-affirmative care.LGBTQ community centers continue to play an important role in supporting the mental health of SGMs. The centers also offer a significant opportunity to lead the way in addressing the substantial unmet mental health needs still facing this population by implementing evidence-based, LGBTQ-affirmative practice through efficient and cost-effective service delivery.

We examined the longitudinal association between blood pressure (BP) and stroke incidence in young and middle-aged adults. BP measured during 9 examinations of the CARDIA study (Coronary Artery Risk Development in Young Adults) from 1985-1986 to 2015-2016 was used to classify participants (n=5079) according to the 2017 Hypertension Clinical Practice Guidelines. We used the highest BP obtained through the third examination (1990–1991) to define baseline BP categories; time-dependent categories (accounting for change in BP over time) were determined incorporating follow-up measurements. BP groups at ages 30 and 40 years were also defined. Stroke events were adjudicated until 2018. Mean age at baseline was 29.8 years. Stroke occurred in 100 participants. Stroke incidence (per 100 000 person-years) was higher ( P

ImportanceCerebral small vessel disease (SVD) causes a quarter of strokes and is the most common pathology underlying vascular cognitive impairment and dementia. An important step to developing new treatments is better trial methodology. Disease mechanisms in SVD differ from other stroke etiologies; therefore, treatments need to be evaluated in cohorts in which SVD has been well characterized. Furthermore, SVD itself can be caused by a number of different pathologies, the most common of which are arteriosclerosis and cerebral amyloid angiopathy. To date, there have been few sufficiently powered high-quality randomized clinical trials in SVD, and inconsistent trial methodology has made interpretation of some findings difficult.ObservationsTo address these issues and develop guidelines for optimizing design of clinical trials in SVD, the Framework for Clinical Trials in Cerebral Small Vessel Disease (FINESSE) was created under the auspices of the International Society of Vascular Behavioral and Cognitive Disorders. Experts in relevant aspects of SVD trial methodology were convened, and a structured Delphi consensus process was used to develop recommendations. Areas in which recommendations were developed included optimal choice of study populations, choice of clinical end points, use of brain imaging as a surrogate outcome measure, use of circulating biomarkers for participant selection and as surrogate markers, novel trial designs, and prioritization of therapeutic agents using genetic data via Mendelian randomization.Conclusions and RelevanceThe FINESSE provides recommendations for trial design in SVD for which there are currently few effective treatments. However, new insights into understanding disease pathogenesis, particularly from recent genetic studies, provide novel pathways that could be therapeutically targeted. In addition, whether other currently available cardiovascular interventions are specifically effective in SVD, as opposed to other subtypes of stroke, remains uncertain. FINESSE provides a framework for design of trials examining such therapeutic approaches.

Patients undergoing evaluation for solid organ transplantation (SOT) often have a history of malignancy. Although the cancer has been treated in these patients, the benefits of transplantation need to be balanced against the risk of tumor recurrence, especially in the setting of immunosuppression. Prior guidelines of when to transplant patients with a prior treated malignancy do not take in to account current staging, disease biology, or advances in cancer treatments. To develop contemporary recommendations, the American Society of Transplantation held a consensus workshop to perform a comprehensive review of current literature regarding cancer therapies, cancer stage-specific prognosis, the kinetics of cancer recurrence, and the limited data on the effects of immunosuppression on cancer-specific outcomes. This document contains prognosis based on contemporary treatment and transplant recommendations for breast, colorectal, anal, urological, gynecological, and nonsmall cell lung cancers. This conference and consensus documents aim to provide recommendations to assist in the evaluation of patients for SOT given a history of a pretransplant malignancy.

Patients undergoing evaluation for solid organ transplantation (SOT) frequently have a history of malignancy. Only patients with treated cancer are considered for SOT but the benefits of transplantation need to be balanced against the risk of tumor recurrence, taking into consideration the potential effects of immunosuppression. Prior guidelines on timing to transplant in patients with a prior treated malignancy do not account for current staging, disease biology, or advances in cancer treatments. To update these recommendations, the American Society of Transplantation (AST) facilitated a consensus workshop to comprehensively review contemporary literature regarding cancer therapies, cancer stage specific prognosis, the kinetics of cancer recurrence, as well as the limited data on the effects of immunosuppression on cancer-specific outcomes. This document contains prognosis, treatment, and transplant recommendations for melanoma and hematological malignancies. Given the limited data regarding the risk of cancer recurrence in transplant recipients, the goal of the AST-sponsored conference and the consensus documents produced are to provide expert opinion recommendations that help in the evaluation of patients with a history of a pretransplant malignancy for transplant candidacy.

BACKGROUND We previously developed molecular assessment systems for lung transplant transbronchial biopsies (TBBs) with high surfactant and bronchial mucosal biopsies, identifying T-cell‒mediated rejection (TCMR) on the basis of the expression of rejection-associated transcripts, but the relationship of rejection to graft loss is unknown. This study aimed to develop molecular assessments for TBBs and mucosal biopsies and to establish the impact of molecular TCMR on graft survival. METHODS We used microarrays and machine learning to assign TCMR scores to an expanded cohort of 457 TBBs (367 high surfactant plus 90 low surfactant) and 314 mucosal biopsies. We tested the score agreement between TBB–TBB, mucosal–mucosal, and TBB–mucosal biopsy pairs in the same patient. We also assessed the association of molecular TCMR scores with graft loss (death or retransplantation) and compared it with the prognostic associations for histology and donor-specific antibodies. RESULTS The molecular TCMR scores assigned in all the TBBs performed similarly to those in high-surfactant TBBs, indicating that variation in alveolation in TBBs does not prevent the detection of TCMR. Mucosal biopsy pieces showed less piece-to-piece variation than TBBs. TCMR scores in TBBs agreed with those in mucosal biopsies. In both TBBs and mucosal biopsies, molecular TCMR was associated with graft loss, whereas histologic rejection and donor-specific antibodies were not. CONCLUSIONS Molecular TCMR can be detected in TBBs regardless of surfactant and in mucosal biopsies, which show less variability in the sampled tissue than TBBs. On the basis of these findings, molecular TCMR appears to be an important predictor of the risk of future graft failure. Trial registration ClinicalTrials.gov NCT02812290.

Systemic racism is a public health crisis. Systemic racism and racial/ethnic injustice produce racial/ethnic disparities in health care and health. Substantial racial/ethnic disparities in stroke care and health exist and result predominantly from unequal treatment. This special report aims to summarize selected interventions to reduce racial/ethnic disparities in stroke prevention and treatment. It reviews the social determinants of health and the determinants of racial/ethnic disparities in care. It provides a focused summary of selected interventions aimed at reducing stroke risk factors, increasing awareness of stroke symptoms, and improving access to care for stroke because these interventions hold the promise of reducing racial/ethnic disparities in stroke death rates. It also discusses knowledge gaps and future directions.

Waridibo E Allison,1 Ada Rubin,2 Trisha V Melhado,1 Aro Choi,1 Deborah A Levine2 1University of Texas Health Science Center San Antonio, Department of Medicine, Division of Infectious Disease, San Antonio, TX, USA; 2New York University, Ronald O. Perelman Department of Emergency Services, New York, NY, USACorrespondence: Waridibo E AllisonDepartment of Medicine, Division of Infectious Disease, University of Texas Health Science Center San Antonio, 7703 Floyd Curl Drive, Mail Code 7881, San Antonio, TX 78229, USATel +1 210 567 0939Fax +1 210 567 4670Email allisonw@uthscsa.eduPurpose: Cervical, oropharyngeal and anogenital cancers are vaccine-preventable diseases, but human papillomavirus (HPV) vaccination coverage in the US remains poor overall with regional variations in vaccination rates. We explore the acceptability by adolescents and their parents of HPV vaccination and text message reminders in the non-traditional setting of the emergency department (ED).Patients and Methods: The modified validated Carolina HPV Attitudes and Beliefs Scale (CHIAS) survey was administered at two urban EDs to adolescents aged 13– 18 years and their parents. Demographic information was collected for each participating adolescent. Recruitment occurred with consecutive eligible participants on the ED census list approached within 4-hour blocks from 8am to 8pm.Results: Ninety-six adolescents completed the survey. The mean adolescent and parental knowledge scores were 63% (SD=29.7) and 60% (SD=22.1), respectively. The higher the HPV knowledge score among both adolescents and parents, the more likely they were to accept HPV vaccine in ED. Among the 10 cases where the parents disagreed to the HPV vaccine and the adolescents agreed to the HPV vaccine, the mean knowledge score among parents disagreeing was 47 compared to 62 among the remaining parents (p=0.04). Sixty-sevenpercent of adolescents and 68% of parents were agreeable to the adolescent receiving vaccination in the ED (kappa = 0.24). Seventy-fivepercent of adolescents and 71% of parents reported being agreeable to receiving text reminders for HPV vaccines (kappa = 0.20). Adolescent agreement with receiving a text message reminder corresponded with an increased willingness to be vaccinated (OR=3.21, 95% CI=1.07– 9.57, p-value=0.0368). Sexually active adolescents were older (mean age, 17 years) than those who reported no sexual activity (mean age, 15 years) (p< 0.0001).Conclusion: Increased knowledge about HPV influences vaccine acceptance. Parents and adolescents may disagree in accepting HPV vaccination. A majority of adolescents and their parents were agreeable to receiving HPV vaccination in the ED and subsequent text message reminders. The ED should be explored further as a non-traditional healthcare setting for HPV vaccination of adolescents.Keywords: adolescent, vaccination, vaccine, prevention, public health

Diagnosing lung transplant rejection currently depends on histologic assessment of transbronchial biopsies (TBB) with limited reproducibility and considerable risk of complications. Mucosal biopsies are safer but not histologically interpretable. Microarray-based diagnostic systems for TBBs and other transplants suggest such systems could assess mucosal biopsies as well. We studied 243 mucosal biopsies from the third bronchial bifurcation (3BMBs) collected from seven centers and classified them using unsupervised machine learning algorithms. Using the expression of a set of rejection-associated transcripts annotated in kidneys and validated in hearts and lung transplant TBBs, the algorithms identified and scored major rejection and injury-related phenotypes in 3BMBs without need for labeled training data. No rejection or injury, rejection, late inflammation, and recent injury phenotypes were thus scored in new 3BMBs. The rejection phenotype correlated with IFNG-inducible transcripts, the hallmarks of rejection. Progressive atrophy-related changes reflected by the late inflammation phenotype in 3BMBs suggest widespread time-dependent airway deterioration, which was especially pronounced after two years posttransplant. Thus molecular assessment of 3BMBs can detect rejection in a previously unusable biopsy format with potential utility in patients with severe lung dysfunction where TBB is not possible and provide unique insights into airway deterioration. ClinicalTrials.gov NCT02812290.

MRI plays an important role as a secondary test or problem-solving modality in the evaluation of adnexal lesions depicted at US. MRI has increased specificity compared with US, decreasing the number of false-positive diagnoses for malignancy and thereby avoiding unnecessary or over-extensive surgery in patients with benign lesions or borderline tumors, while women with possible malignancies can be expeditiously referred for oncologic surgical evaluation. The Ovarian-Adnexal Reporting and Data System (O-RADS) MRI Committee is an international collaborative effort formed under the direction of the American College of Radiology and includes a diverse group of experts on adnexal imaging and management who developed the O-RADS MRI risk stratification system. This scoring system assigns a probability of malignancy based on the MRI features of an adnexal lesion and provides information to facilitate optimal patient management. The widespread implementation of a codified reporting system will lead to improved interpretation agreement and standardized communication between radiologists and referring physicians. In addition, it will allow for high-quality multi-institutional collaborations—an important unmet need that has hampered the performance of high-quality research in this area in the past. This article provides guidelines on using the O-RADS MRI risk stratification system in clinical practice, as well as in the educational and research settings. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Levine in this issue.

Background Reach Out is a factorial trial studying multicomponent behavioral interventions to reduce blood pressure in hypertensive emergency department patients. The original study protocol was published in June 2020. Here, we describe the updated protocol, including a supplemental study, Reach Out Cognition. Reach Out Cognition is a remote study that will assess the acceptability, feasibility, and satisfaction of digital, self-administered cognitive assessments and Bluetooth-enabled, self-measured blood pressure monitoring in the Reach Out population. We will also estimate the prevalence of mild cognitive impairment in Reach Out participants. Methods Reach Out Cognition includes remote enrollment and follow-up assessments. Reach Out Cognition extends Reach Out data collection past the current 12 months to 15 and 18 months. Participants will be Reach Out participants who complete their 12-month outcome assessments and opt to continue in the cohort study. Participants will continue to receive the Reach Out intervention, consisting of (1) daily healthy behavior text messaging and (2) weekly self-measured blood pressure monitoring. Blood pressure will be measured using Bluetooth-enabled self-measured blood pressure monitoring devices, and cognition will be measured using digital self-administered cognitive assessments at 12, 15, and 18 months. Discussion Reach Out Cognition will explore the potential of remote, digital, self-administered assessments of blood pressure and cognition among predominantly working-age Black Americans. Reach Out Cognition will inform future clinical trials and clinical remote monitoring of blood pressure and cognition that may lead to new approaches to treating and reducing hypertension and cognitive disparities. Trial registration ClinicalTrials.gov NCT03422718. The record was first available to the public on January 30, 2018, prior to the enrollment of patients on March 25, 2019.

OBJECTIVES To evaluate the growth rate of benign ovarian cystadenomas and the degree of variability in ultrasound measurements. METHODS Two independent retrospective cohorts of women found to have benign cystadenomas at surgery were identified. To assess growth rate, ultrasounds on women in a community-based health system were reviewed and the growth rate was determined based on the maximum reported size dimension using a mixed effect model. To assess measurement variability, two radiologists independently measured presurgical adnexal imaging findings for women in a tertiary care referral setting. Interobserver, intra-observer, and intermodality (cine clip versus still images) variability in measurements was determined using correlation coefficients (CC) and Bland-Altman analysis, with the proportion of measurements varying by more than 1 cm calculated. RESULTS For growth rate assessment, 405 women with 1412 ultrasound examinations were identified. The median growth rate was 0.65 cm/year with mucinous cystadenomas growing faster at 0.83 cm/year compared to 0.51 cm/year for serous cystadenomas (median test P

As a marker of underlying lung allograft injury, donor-derived cell-free DNA (dd-cfDNA) may be used to identify episodes of acute allograft injury in lung transplant recipients. We investigated the utility of dd-cfDNA to monitor subjects at risk of acute rejection or infection in routine clinical practice.This multicenter, retrospective cohort study collected data from lung transplant recipients within 3 years of transplant at 4 centers between March 24, 2020 and September 1, 2020. During this period, as part of routine care during the COVID-19 pandemic, these centers implemented a home-based surveillance program using plasma dd-cfDNA in preference to surveillance bronchoscopy. Dd-cfDNA was used to detect acute lung allograft dysfunction (ALAD) - a composite endpoint of acute rejection and infection. dd-cfDNA levels in patients with ALAD were compared to stable patients. The performance characteristics of dd-cfDNA ≥ 1.0% to detect ALAD were estimated.A total of 175 patients underwent 380 dd-cfDNA measurements, of which 290 were for routine surveillance purposes. dd-cfDNA was higher in patients with ALAD than stable patients (Median (IQR) 1.7% (0.63, 3.1) vs 0.35% (0.22, 0.79), p0.001). As an indication of underlying ALAD during surveillance testing, the estimated sensitivity of dd-cfDNA ≥1% was 73.9%, specificity of 87.7%, positive predictive value of 43.4% and negative predictive value of 96.5%.dd-cfDNA identified acute lung allograft dysfunction in asymptomatic lung transplant patients that may not have been identified by using a clinically indicated biopsy strategy alone. dd-cfDNA1.0% may be useful in ruling out acute rejection and infection, supporting its use as a potential noninvasive marker for surveillance monitoring.

Objective We present a blueprint for the reallocation of pediatric emergency resources in response to the COVID-19 pandemic. Methods New York-Presbyterian Hospital - Weill Cornell Medical Center is an urban, quaternary, academic medical center, a level 1 trauma center, and a regional burn center located in New York City. The novel coronavirus (COVID-19) pandemic created a unique challenge for pediatric emergency medicine. As the crisis heightened for adult patients, pediatric emergency services experienced a significant decline in volume and acuity. Results We offer guidelines to modify physical space, clinical services, staffing models, and the importance of steady leadership. Pediatric emergency space was converted to adult COVID-19 beds, necessitating the repurposing of nonclinical areas for pediatric patients. Efficient clinical pathways were created in collaboration with medical and surgical subspecialists for expedited emergency care of children. We transitioned staffing models to meet the changing clinical demands of the emergency department by both reallocation of pediatric emergency medicine providers to telemedicine and by expanding their clinical care to adult patients. Concentrated communication and receptiveness by hospital and department leadership were fundamental to address the dynamic state of the pandemic and ensure provider wellness. Conclusions Modification of physical space, clinical services, staffing models, and the importance of steady leadership enabled us to maintain outstanding clinical care for pediatric patients while maximizing capacity and service for adult COVID-19 patients in the emergency department.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is a major limitation in the long-term survival of lung transplant recipients (LTRs). However, the risk factors in the development of BOS remain undetermined. We conducted an international cohort study of LTRs to assess whether Aspergillus colonization with large or small conidia is a risk factor for the development of BOS.METHODS: Consecutive LTRs from January 2005 to December 2008 were evaluated. Rates of BOS and associated risk factors were recorded at 4 years. International Society of Heart and Lung Transplantation criteria were used to define fungal and other infections. A Cox proportional-hazards-model was constructed to assess the association between Aspergillus colonization and the development of BOS controlling for confounders.RESULTS: A total of 747 LTRs were included. The cumulative incidence of BOS at 4 years after transplant was 33% (250 of 747). Additionally, 22% of LTRs experienced Aspergillus colonization after transplantation. Aspergillus colonization with either large (hazard ratio [HR] = 0.6, 95% confidence interval [CI] = 0.3-1.2, p = 0.12) or small conidia (HR = 0.9, 95% CI = 0.6-1.4, p = 0.74) was not associated with the development of BOS. Factors associated with increased risk of development of BOS were the male gender (HR = 1.4, 95% CI = 1.1-1.8, p = 0.02) and episodes of acute rejection (1-2 episodes, HR = 1.5, 95% CI = 1.1-2.1, p = 0.014; 3-4 episodes, HR = 1.6, 95% CI = 1.0-2.6, p = 0.036; >4 episodes, HR = 2.2, 95% CI = 1.1-4.3, p = 0.02), whereas tacrolimus use was associated with reduced risk of BOS (HR = 0.6, 95% CI = 0.5-0.9, p = 0.007).CONCLUSIONS: We conclude from this large multicenter cohort of lung transplant patients, that Aspergillus colonization with large or small conidia did not show an association with the development of BOS.