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Background: This was a single-center pilot study to determine the safety and efficacy of transplanting lungs from hepatitis B virus (HBV) nucleic acid positive (NAT+) donors to HBV vaccinated (sAb+) candidates. We report our study experience, including barriers to utilizing NAT+ donors., Methods: Primary candidate eligibility criteria included: HBV sAb+, < 70 years old, not on mechanical support, no liver fibrosis, normal esophageal motility, and cPRA < 60. Only brain-dead donors with no marginal characteristics or concurrent hepatitis C virus (HCV) were accepted. Recipients of HBV NAT+ organs would receive intravenous hepatitis B immunoglobulin as well as appropriate HBV antiviral therapy., Results: A total of 155 patients were screened for eligibility. Most (64.5%) were excluded because they were HBV sAb negative. Of the 25 eligible sAb+ candidates, 13 enrolled, and 6 were listed for HBV NAT+ organs. There were 16 donor offers, all of which were rejected because of quality or concurrent donor HCV infection. No other centers utilized these organs., Conclusions: Reduced enrollment related to strict eligibility criteria, few HBV immune candidates, and stringent requirements on HBV NAT+ donors were limiting factors. Further studies are needed to assess the safety and efficacy of HBV NAT+ donor lung transplants., (© 2025 Wiley Periodicals LLC.)

Background: Anterior cruciate ligament reconstruction (ACLR) is a commonly performed orthopaedic procedure. As the number of ACLRs continues to increase in incidence, understanding the variability and drivers of cost to the health care system may help target cost-saving measures., Purposes: To examine the variability in overall 90-day reimbursements (amount paid for health care services) for ACLR using a national, multi-insurance, administrative database and to assess factors associated with variability., Study Design: Cross-sectional study., Methods: Using the M151 PearlDiver data set (data from 2010 to April 30, 2021), the authors identified the 90-day total reimbursements in patients who underwent ACLR. Patient age, sex, and comorbidity burden; insurance type; inpatient versus outpatient surgery status; and 90-day postoperative adverse events were determined and were correlated with overall reimbursements using multivariable logistic regression., Results: A total of 249,484 patients who underwent ACLR during the study period were identified. The mean patient age was 31.6 ± 13.58 years, 50.3% were female, the mean Elixhauser Comorbidity Index (ECI) was 1.4 ± 1.8, and procedures were performed on an outpatient basis for 245,507 patients (98.4%). Insurance type was commercial for 220,284 patients (88.3%), Medicaid for 17,660 (7.1%), and Medicare for 3500 (1.4%). The mean overall 90-day reimbursement was $4281.91 ± $4982.61 (median [interquartile range], $3032 [$1681-5142]), and the total reimbursement for the patient cohort was $1,049,250,747. On multivariable linear regression, the variables independently associated with the greatest changes in overall reimbursement were (in decreasing order) hospital readmission (+$17,675.23), adverse events (+$1554.14), inpatient procedure (+$1246.51), and emergency department visits (+$784.06). Lesser but significant associations were found with greater ECI (+$252.30) and female sex (+$101.01). Decreased overall reimbursement was associated with older age (-$12.19) and Medicare (-$883.48)/Medicaid (-$493.18) relative to commercial insurance., Conclusion: In the current study, large variability was found in overall ACLR reimbursement/cost within the health care system. Hospital admissions (inpatient surgery and readmission) and adverse events were associated with the greatest increase in costs and emphasize the need to optimize these metrics above and beyond patient experience., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: S.J.H. received grant support from the Jane Danowski Weiss Family Foundation Fund at Yale University School of Medicine. M.M.D. received grant support from the Richard K. Gershon, M.D. Fund at Yale University School of Medicine. E.S. has received education payments from Gotham Surgical. M.J.M. has received consulting fees and nonconsulting fees from Smith+Nephew. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2024.)

Transition to circular economy for lithium-ion batteries used in electric vehicles requires integrating multiple stages of the value cycle. However, strategies aimed at extending the lifetime of batteries are not yet sufficiently considered within the European battery industry, particularly regarding repurposing. Using second-life lithium-ion batteries (SLBs) before subsequent recycling can offer several advantages, such as the development of sustainable business models, the reduction of emissions, and alignment with UN Sustainable Development Goals 7, 12, and 13. Using expert and problem-centred interviews along with an exploratory workshop, this study guides stakeholders in the battery sector by illustrating the necessary changes for a more holistic circular economy. Moreover, an extended political, economic, social, technological, environmental, legal, and additionally safety-related (PESSTEL) analysis approach is carried out, which has not yet been used in this context. In this process, barriers, as well as necessary institutional framework conditions and organisational requirements for a successful market entry of SLB applications are investigated. Among others, key barriers relate to the competition with first-life applications and safety concerns. SLBs require high manual labour costs for repurposing, along with expenses for expired warranties and re-certifications. Ownership structures in traditional business models often result in SLBs and their corresponding usage data staying under the control of the manufacturers. Market viability, however, requires a level playing field for both first-life and second-life operators as well as circular battery and data-sharing business models. Gathering data on the ageing performance and performing improved safety testing according to test protocols facilitates the reliable assessment of SLBs., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: The natural history of primary sclerosing cholangitis (PSC) among African Americans (AA) is not well understood., Methods: Transplant-free survival and hepatic decompensation-free survival were assessed using a retrospective research registry from 16 centers throughout North America. Patients with PSC alive without liver transplantation after 2008 were included. Diagnostic delay was defined from the first abnormal liver test to the first abnormal cholangiogram/liver biopsy. Socioeconomic status was imputed by the Zip code., Results: Among 850 patients, 661 (77.8%) were non-Hispanic Whites (NHWs), and 85 (10.0%) were AA. There were no significant differences by race in age at diagnosis, sex, or PSC type. Inflammatory bowel disease was more common in NHWs (75.8% vs. 51.8% p=0.0001). The baseline (median, IQR) Amsterdam-Oxford Model score was lower in NHWs (14.3, 13.4-15.2 vs. 15.1, 14.1-15.7, p=0.002), but Mayo risk score (0.03, -0.8 to 1.1 vs. 0.02, -0.7 to 1.0, p=0.83), Model for End-stage Liver Disease (5.9, 2.8-10.7 vs. 6.4, 2.6-10.4, p=0.95), and cirrhosis (27.4% vs. 27.1%, p=0.95) did not differ. Race was not associated with hepatic decompensation, and after adjusting for clinical variables, neither race nor socioeconomic status was associated with transplant-free survival. Variables independently associated with death/liver transplant (HR, 95% CI) included age at diagnosis (1.04, 1.02-1.06, p<0.0001), total bilirubin (1.06, 1.04-1.08, p<0.0001), and albumin (0.44, 0.33-0.61, p<0.0001). AA race did not affect the performance of prognostic models., Conclusions: AA patients with PSC have a lower rate of inflammatory bowel disease but similar progression to hepatic decompensation and liver transplant/death compared to NHWs., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Purpose: The murine oxygen-induced retinopathy (OIR) model is one of the most widely used animal models of ischemic retinopathy, mimicking hallmark pathophysiology of initial vaso-obliteration (VO) resulting in ischemia that drives neovascularization (NV). In addition to NV and VO, human ischemic retinopathies, including retinopathy of prematurity (ROP), are characterized by increased vascular tortuosity. Vascular tortuosity is an indicator of disease severity, need to treat, and treatment response in ROP. Current literature investigating novel therapeutics in the OIR model often report their effects on NV and VO, and measurements of vascular tortuosity are less commonly performed. No standardized quantification of vascular tortuosity exists to date despite this metric's relevance to human disease. This proof-of-concept study aimed to apply a previously published semi-automated computer-based image analysis approach (iROP-Assist) to develop a new tool to quantify vascular tortuosity in mouse models., Design: Experimental study., Subjects: C57BL/6J mice subjected to the OIR model., Methods: In a pilot study, vasculature was manually segmented on flat-mount images of OIR and normoxic (NOX) mice retinas and segmentations were analyzed with iROP-Assist to quantify vascular tortuosity metrics. In a large cohort of age-matched (postnatal day 12 [P12], P17, P25) NOX and OIR mice retinas, NV, VO, and vascular tortuosity were quantified and compared. In a third experiment, vascular tortuosity in OIR mice retinas was quantified on P17 following intravitreal injection with anti-VEGF (aflibercept) or Immunoglobulin G isotype control on P12., Main Outcome Measures: Vascular tortuosity., Results: Cumulative tortuosity index was the best metric produced by iROP-Assist for discriminating between OIR mice and NOX controls. Increased vascular tortuosity correlated with disease activity in OIR. Treatment of OIR mice with aflibercept rescued vascular tortuosity., Conclusions: Vascular tortuosity is a quantifiable feature of the OIR model that correlates with disease severity and may be quickly and accurately quantified using the iROP-Assist algorithm., Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (© 2023 by the American Academy of Ophthalmology.)

SHELTER is a trial of transplanting lungs from deceased donors with hepatitis C virus (HCV) infection into HCV-negative candidates (sponsor: Merck; NCT03724149). Few trials have reported outcomes using thoracic organs from HCV-RNA + donors and none have reported quality of life (QOL)., Methods: This study is a single-arm trial of 10 lung transplants at a single center. Patients were included who were between 18 and 67 y of age and waitlisted for lung-only transplant. Patients were excluded who had evidence of liver disease. Primary outcome was HCV cure (sustained virologic response 12 wk after completing antiviral therapy). Recipients longitudinally reported QOL using the validated RAND-36 instrument. We also applied advanced methods to match HCV-RNA + lung recipients to HCV-negative lung recipients in a 1:3 ratio at the same center., Results: Between November 2018 and November 2020, 18 patients were consented and opted-in for HCV-RNA + lung offers in the allocation system. After a median of 37 d (interquartile range [IQR], 6-373) from opt-in, 10 participants received double lung transplants. The median recipient age was 57 y (IQR, 44-67), and 7 recipients (70%) had chronic obstructive pulmonary disease. The median lung allocation score at transplant was 34.3 (IQR, 32.7-86.9). Posttransplant, 5 recipients developed primary graft dysfunction grade 3 on day 2 or 3, although none required extracorporeal membrane oxygenation. Nine patients received elbasvir/grazoprevir, whereas 1 patient received sofosbuvir/velpatasvir. All 10 patients were cured of HCV and survived to 1 y (versus 83% 1-y survival among matched comparators). No serious adverse events were found to be related to HCV or treatment. RAND-36 scores showed substantial improvement in physical QOL and some improvement in mental QOL. We also examined forced expiratory volume in 1 s-the most important lung function parameter after transplantation. We detected no clinically important differences in forced expiratory volume in 1 s between the HCV-RNA + lung recipients versus matched comparators., Conclusions: SHELTER adds important evidence regarding the safety of transplanting HCV-RNA + lungs into uninfected recipients and suggests QOL benefits., (Copyright © 2023 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

We present a case of cardiac sarcoidosis with persistent, focal fluorodeoxyglucose uptake at the left ventricular apical aneurysm concerning for ongoing active inflammatory injury, prompting aggressive immunosuppressive therapy. This case highlights the importance of understanding the various clinical entities that may resemble disease activity on fluorodeoxyglucose positron emission tomography/computed tomography imaging. ( Level of Difficulty: Intermediate. )., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

Background: Historically, many organs from deceased donors with hepatitis C virus (HCV) were discarded. The advent of highly curative direct-acting antiviral (DAA) therapies motivated transplant centers to conduct trials of transplanting HCV-viremic organs (nucleic acid amplification test positive) into HCV-negative recipients, followed by DAA treatment. However, the factors that influence candidates' decisions regarding acceptance of transplant with HCV-viremic organs are not well understood., Methods: To explore patient-level perceptions, influences, and experiences that inform candidate decision-making regarding transplant with organs from HCV-viremic donors, we conducted a qualitative semistructured interview study embedded within 3 clinical trials investigating the safety and efficacy of transplanting lungs and kidneys from HCV-viremic donors into HCV-negative recipients. The study was conducted from June 2019 to March 2021., Results: Among 44 HCV-negative patients listed for organ transplant who were approached for enrollment in the applicable clinical trial, 3 approaches to decision-making emerged: positivist, risk analyses, and instinctual response. Perceptions of risk contributed to conceptualizations of factors influencing decisions. Moreover, most participants relied on multiple decision-making approaches, either simultaneously or sequentially., Conclusions: Understanding how different decisional models influence patients' choices regarding transplant with organs from HCV-viremic donors may promote shared decision-making among transplant patients and providers., Competing Interests: P.P.R. and D.S.G. received investigator-initiated and collaborative grants from Merck, AbbVie, and Gilead to the University of Pennsylvania in support of trials of transplanting HCV-viremic organs into HCV-negative recipients followed by antiviral treatment. P.P.R., D.S.G., J.M.D., M.M.C., and C.B. received investigator-initiated grant funding from Merck to the University of Pennsylvania in support of a trial of transplanting HCV-viremic lungs into HCV-negative recipients followed by antiviral treatment. The other authors declare no conflicts of interest., (Copyright © 2022 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Background and Objective: To report the outcomes of topical difluprednate 0.05% use in the closure of full-thickness macular holes., Patients and Methods: Retrospective chart review of 4 patients with full-thickness macular holes who received difluprednate drops 4 times daily for a minimum of 12 weeks. Main outcome measures were macular hole status assessed with optical coherence tomography, visual acuity, intraocular pressure, and complications of treatment., Results: All patients had macular hole closure within 12 weeks of difluprednate exposure. Mean time to macular hole closure was 5 weeks (range, 2-12 weeks). Visual acuity improved with macular hole closure. Average baseline visual acuity was 20/42. Average visual acuity after macular hole closure was 20/26 (P = 0.14). Two patients experienced increased intraocular pressure with topical steroid use., Conclusion: Exposure to difluprednate in this cohort of patients with full-thickness macular holes was associated with reduced macular edema, macular hole closure, and visual improvement.

Introduction: The toy industry has grown substantially over time, with billions of dollars of toys sold each year in the United States alone. Even after safety considerations, injuries can result. This study examined toy-related fractures in the US Emergency Departments (ED)., Methods: The 1999 to 2018 National Electronic Injury Surveillance System from the US Consumer Product Safety Commission was examined data for fractures involving a toy-related injury. The incidence, trends, and anatomic locations for such fractures were assessed., Results: In total, 347,135 toy-related fractures were identified, of which 237,754 (68%) were in patients younger than 18 years, 182,516 (53%) were sustained by male subjects, and a 95% yearly incidence increase was observed over the years of the study. Anatomically, 37% were shoulder/arm/elbow, 24% wrist/hand/finger, 19% ankle/toe/foot, 10% leg/knee, 6% face/neck/head, and 4% trunk/pubic region., Discussion: Despite safety considerations with toy design, more than a third of toy-related fractures were seen in the ED, with a nearly doubling yearly incidence over the study period. This could be contributed to by increased production and prevalence of toys and/or rougher play and increased overall violence. These results are important not only for patient safety but also for orthopaedic surgeons, EDs, toy manufacturers, and policymakers., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.)

Background and Objective: The purpose of this article is to describe a cluster of four cases of severe postoperative inflammation in eyes that received intraoperative indocyanine green (ICG) from the same lot., Patients and Methods: This was a retrospective chart review of patients from a single-center, retina-only group practice. The ICG lot associated with the inflammatory events was identified and analyzed with high-performance liquid chromatography with UV spectroscopy., Results: Four patients presented on postoperative day 1 with severe inflammation. The first patient was treated with aqueous biopsy and injection of intravitreal antibiotics, followed by topical steroid and antibiotic drops. The subsequent three patients were treated with topical steroid and antibiotic drops. All patients had resolution of inflammation by postoperative day 14 (range 10 to 14 days). High-performance liquid chromatography with UV spectroscopy failed to identify a contaminant., Conclusions: The use of intravitreal ICG dye as a surgical adjuvant may uncommonly be associated with severe postoperative inflammation. This inflammation may resolve within weeks after topical corticosteroid and antibiotic treatment. [ Ophthalmic Surg Lasers Imaging Retina . 2022;53:148-151.] .

The emissions of tyre wear particles (TWPs) into the environment are increasing and have negative impacts on the environment and human health. The aim of this study was therefore to establish a mass balance for vehicle tyres und TWP emissions in Austria using static material flow analysis, which enabled a quantification of mass flows of rubber including carbon black as the most mass-relevant tyre filler. Vehicle-specific and mileage-dependent emission factors were used to calculate the TWP emissions. The results for the year 2018 indicate that 80% of the tyre rubber remained in use, while 14% was re-treaded, recycled, incinerated or exported as end-of-life tyres and 6% was emitted as TWPs to air, soil or surface water. Of these 21,200 t/y released and dissipative lost TWPs, 6% were microscale, with a possible size between 0.1 and 10 μm, and 0.3% were nanoscale below 0.1 μm. The mass balance on the substance level shows that the TWPs contained 5,500 t/y of carbon black emitted in the form of airborne TWPs (6%) or entering in the soil or surface waters (47% each). Regarding air pollution from road vehicles, about 3,600 t/y were non-exhaust emissions, including tyre, brake and road-surface wear, which contributed to 9% of total dust emissions across Austria. Scenario analysis for 2050 with regard to e-mobility and the European Green Deal reveals that non-exhaust emissions can only be significantly reduced by a general reduction of the mileage or an environmentally friendly tyre design. This modelling approach provides a solid basis for decision makers in traffic planning as well as for chemical risk assessment. However, dynamic models with higher temporal and spatial resolution are needed to predict future mass flows of TWPs and their environmental fate, including their degradation products and possible accumulation effects., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Focused cardiac ultrasound (FCU) is a safe and efficient diagnostic intervention for internal medicine physicians. FCU is a highly teachable skill, but is used in routine cardiac assessment in only 20% of surveyed training programs.We developed an FCU curriculum for internal medicine residents and an assessment tool to evaluate the impact of the curriculum on trainee knowledge and confidence. Methods: Internal medicine residents rotating through clinical cardiology services underwent 30 minutes of didactic and 60 minutes of hands-on teaching on acquisition and interpretation of FCU. A 20 item pre and post-curriculum online survey was administered (November 2018-December 2019) to assess confidence and knowledge in FCU. Results: 79 of 116 (68%) residents completed the pre-survey and 50 completed the post-survey, of whom 34 received the curriculum. The mean change in confidence score in those who received versus did not receive the curriculum was 0.99 versus 0.39 (p=0.046) on a 5-point Likert scale. Among 33 residents who had paired pre- and post-surveys the mean change in confidence score was 1.2 versus 0.85 (p<0.001) in those who received versus did not receive the curriculum. The mean increase in knowledge score was 13% versus 7% respectively (p<0.0001). Conclusions: We instituted a novel curriculum for internal medicine residents to gain experience in image acquisition and interpretation. Both confidence and knowledge in FCU improved following the curriculum, indicating that this is a highly teachable skill. Additional analysis of the of the FCU study images will be useful for informing future interventions., Competing Interests: The authors declare no conflicts of interest., (Author(s) retain the copyright for their work.)

Purpose: The Covid-19 pandemic is a public health emergency with both physical and mental health risks. Medical students have baseline elevated rates of anxiety, depression and burnout. As such, they may be especially susceptible to the psychological stresses of Covid-19. The current study aimed to evaluate the prevalence of anxiety and depression among United States medical students during the Covid-19 pandemic., Methods: A cross-sectional, survey-based study collected demographic data as well as the 7-item Generalized Anxiety Disorder (GAD-7) and the 9-item Patient Health Questionnaire (PHQ-9) to assess anxiety and depression symptoms, respectively. The survey was administered from April 13, 2020 to April 28, 2020 amidst the height of the Covid-19 pandemic., Results: A total of 1,428 students from 40 US medical schools completed the survey. From those surveyed, 30.6% and 24.3% of respondents screened positive for anxiety and depression, respectively. Median GAD-7 scores were higher among females (7.0 vs 5.0, P  < .00001), pre-clinical students (7.0 vs 6.0, P  < .00004), and those with a friend or relative diagnosed with Covid-19 (7.0 vs 6.0, P =.001). Median PHQ-9 scores were higher among females (6.0 vs 4.0, P  < .00001) and pre-clinical students (6.0 vs 4.0, P  < .00001)., Conclusion: When compared to previous medical student studies, these results are 61% higher for anxiety and 70% higher for depression during the Covid-19 era. The current study suggests that there should be a heightened awareness of and sensitivity to student's mental health during the Covid-19 pandemic with certain cohorts at greater potential risk., Competing Interests: Declaration of conflicting interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Background: Single-center trials and retrospective case series have reported promising outcomes using kidneys from donors with hepatitis C virus (HCV) infection. However, multicenter trials are needed to determine if those findings are generalizable., Methods: We conducted a prospective trial at seven centers to transplant 30 kidneys from deceased donors with HCV viremia into HCV-uninfected recipients, followed by 8 weeks of once-daily coformulated glecaprevir and pibrentasvir, targeted to start 3 days posttransplant. Key outcomes included sustained virologic response (undetectable HCV RNA 12 weeks after completing treatment with glecaprevir and pibrentasvir), adverse events, and allograft function., Results: We screened 76 patients and enrolled 63 patients, of whom 30 underwent kidney transplantation from an HCV-viremic deceased donor (median kidney donor profile index, 53%) in May 2019 through October 2019. The median time between consent and transplantation of a kidney from an HCV-viremic donor was 6.3 weeks. All 30 recipients achieved a sustained virologic response. One recipient died of complications of sepsis 4 months after achieving a sustained virologic response. No severe adverse events in any patient were deemed likely related to HCV infection or treatment with glecaprevir and pibrentasvir. Three recipients developed acute cellular rejection, which was borderline in one case. Three recipients developed polyomavirus (BK) viremia near or >10,000 copies/ml that resolved after reduction of immunosuppression. All recipients had good allograft function, with a median creatinine of 1.2 mg/dl and median eGFR of 57 ml/min per 1.73 m 2 at 6 months., Conclusions: Our multicenter trial demonstrated safety and efficacy of transplantation of 30 HCV-viremic kidneys into HCV-negative recipients, followed by early initiation of an 8-week regimen of glecaprevir and pibrentasvir., (Copyright © 2020 by the American Society of Nephrology.)

Background: Hepatic epithelioid hemangioendothelioma (HEHE) is a rare vascular tumor with a high mortality rate. HEHE is now a formally recognized indication for exception point priority in the United States under the new National Liver Review Board. The role of liver transplantation (LT) and exception point waitlist priority in the United States for patients with HEHE remains understudied., Methods: This was a retrospective cohort study using the United Network for Organ Sharing transplant database. From February 27, 2002 to January 31, 2018, 131 adults waitlisted for LT with HEHE were identified by free-text entry., Results: Exception point applications were submitted for 91.6% (120/131) of patients. All patients with fully reviewed applications received exception points at least once during waitlisting, and 85% (103/120) upon first submission. Among the 88 patients transplanted, median model for end-stage liver disease score at LT was 7 ((interquartile range [IQR]: 6-11) and waiting time 78.5 days (IQR: 29.5-237.5). Unadjusted post-LT survival of HEHE recipients at 1-, 3-, and 5-years from LT was 88.6%, 78.9%, and 77.2%. Unadjusted post-LT patient and graft survival of HEHE patients was not different from patients with hepatocellular carcinoma within Milan receiving exception point priority (P = 0.08). An increased rate of graft failure due to hepatic artery thrombosis ≤14 days from initial LT was observed in HEHE versus non-HEHE patients (4.6% versus 0.5%)., Conclusions: The majority of HEHE recipients receive exception points at a universal approval rate allowing prompt access to deceased donor LT.

Background: Better risk stratification strategies are needed to enhance clinical care and trial design in heart failure with preserved ejection fraction (HFpEF)., Objectives: The purpose of this study was to assess the value of a targeted plasma multi-marker approach to enhance our phenotypic characterization and risk prediction in HFpEF., Methods: In this study, the authors measured 49 plasma biomarkers from TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial participants (n = 379) using a Multiplex assay. The relationship between biomarkers and the risk of all-cause death or heart failure-related hospital admission (DHFA) was assessed. A tree-based pipeline optimizer platform was used to generate a multimarker predictive model for DHFA. We validated the model in an independent cohort of HFpEF patients enrolled in the PHFS (Penn Heart Failure Study) (n = 156)., Results: Two large, tightly related dominant biomarker clusters were found, which included biomarkers of fibrosis/tissue remodeling, inflammation, renal injury/dysfunction, and liver fibrosis. Other clusters were composed of neurohormonal regulators of mineral metabolism, intermediary metabolism, and biomarkers of myocardial injury. Multiple biomarkers predicted incident DHFA, including 2 biomarkers related to mineral metabolism/calcification (fibroblast growth factor-23 and OPG [osteoprotegerin]), 3 inflammatory biomarkers (tumor necrosis factor-alpha, sTNFRI [soluble tumor necrosis factor-receptor I], and interleukin-6), YKL-40 (related to liver injury and inflammation), 2 biomarkers related to intermediary metabolism and adipocyte biology (fatty acid binding protein-4 and growth differentiation factor-15), angiopoietin-2 (related to angiogenesis), matrix metalloproteinase-7 (related to extracellular matrix turnover), ST-2, and N-terminal pro-B-type natriuretic peptide. A machine-learning-derived model using a combination of biomarkers was strongly predictive of the risk of DHFA (standardized hazard ratio: 2.85; 95% confidence interval: 2.03 to 4.02; p < 0.0001) and markedly improved the risk prediction when added to the MAGGIC (Meta-Analysis Global Group in Chronic Heart Failure Risk Score) risk score. In an independent cohort (PHFS), the model strongly predicted the risk of DHFA (standardized hazard ratio: 2.74; 95% confidence interval: 1.93 to 3.90; p < 0.0001), which was also independent of the MAGGIC risk score., Conclusions: Various novel circulating biomarkers in key pathophysiological domains are predictive of outcomes in HFpEF, and a multimarker approach coupled with machine-learning represents a promising strategy for enhancing risk stratification in HFpEF., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to assess if clinical phenogroups differ in comprehensive biomarker profiles, cardiac and arterial structure/function, and responses to spironolactone therapy., Background: Previous studies identified distinct subgroups (phenogroups) of patients with heart failure with preserved ejection fraction (HFpEF)., Methods: Among TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial) participants, we performed latent-class analysis to identify HFpEF phenogroups based on standard clinical features and assessed differences in multiple biomarkers measured from frozen plasma; cardiac and arterial structure/function measured with echocardiography and arterial tonometry; prognosis; and response to spironolactone., Results: Three HFpEF phenogroups were identified. Phenogroup 1 (n = 1,214) exhibited younger age, higher prevalence of smoking, preserved functional class, and the least evidence of left ventricular (LV) hypertrophy and arterial stiffness. Phenogroup 2 (n = 1,329) was older, with normotrophic concentric LV remodeling, atrial fibrillation, left atrial enlargement, large-artery stiffening, and biomarkers of innate immunity and vascular calcification. Phenogroup 3 (n = 899) demonstrated more functional impairment, obesity, diabetes, chronic kidney disease, concentric LV hypertrophy, high renin, and biomarkers of tumor necrosis factor-alpha-mediated inflammation, liver fibrosis, and tissue remodeling. Compared with phenogroup 1, phenogroup 3 exhibited the highest risk of the primary endpoint of cardiovascular death, heart failure hospitalization, or aborted cardiac arrest (hazard ratio [HR]: 3.44; 95% confidence interval [CI]: 2.79 to 4.24); phenogroups 2 and 3 demonstrated similar all-cause mortality (phenotype 2 HR: 2.36; 95% CI: 1.89 to 2.95; phenotype 3 HR: 2.26, 95% CI: 1.77 to 2.87). Spironolactone randomized therapy was associated with a more pronounced reduction in the risk of the primary endpoint in phenogroup 3 (HR: 0.75; 95% CI: 0.59 to 0.95; p for interaction = 0.016). Results were similar after excluding participants from Eastern Europe., Conclusions: We identified important differences in circulating biomarkers, cardiac/arterial characteristics, prognosis, and response to spironolactone across clinical HFpEF phenogroups. These findings suggest distinct underlying mechanisms across clinically identifiable phenogroups of HFpEF that may benefit from different targeted interventions., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background and Objective: To investigate the variability in optical coherence tomography angiography (OCTA) image interpretation in a cohort of retina specialists., Patients and Methods: A survey consisting of a study set of images from 12 eyes examined by OCTA was created. Eight multiple-choice answers were provided as response options for each case. The survey was sent to 100 retina specialists, with instructions to complete the survey only if they had facility with the interpretation of OCTA images. Thirty-eight physicians completed the survey. Data generated were subsequently analyzed and interpreted., Results: Krippendorff's alpha coefficients of agreement and their associated 95% confidence intervals (CIs) were utilized for statistical analyses. For the overall data, the estimated alpha coefficient was 0.366 (95% CI, 0.31-0.47). Although the estimated alpha coefficient is significant, the level of significance is considered low, as it is far from unity (0.366). Therefore, although statistically significant, the overall data did not demonstrate either high reliability or agreement in interpretation. Additional analyses evaluating the influence of years and location of practice, and frequency of OCTA use did not demonstrate a significant effect on reliability measures., Conclusions: Significant variability exists in the interpretation of OCTA images in this cohort of retina specialists. The overall data did not demonstrate high reliability or agreement in interpretation of images, suggesting the need for additional study of this nascent technology. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:344-353.]., (Copyright 2019, SLACK Incorporated.)

Background Heart failure ( HF ) with "recovered" ejection fraction ( HF rec EF ) is an emerging phenotype, but no tools exist to predict ejection fraction ( EF ) recovery in acute HF . We hypothesized that indices of baseline cardiac structure and function predict HF rec EF in nonischemic cardiomyopathy and reduced EF . Methods and Results We identified a nonischemic cardiomyopathy cohort with EF <40% during the first HF hospitalization (n=166). We performed speckle-tracking echocardiography to measure longitudinal, circumferential, and radial strain, and the average of these measures (myocardial systolic performance). HF rec EF was defined as follow-up EF ≥40% and ≥10% improvement from baseline EF . Fifty-nine patients (36%) achieved HF rec EF (baseline EF 26±7%; follow-up EF 51±7%) within a median of 135 (interquartile range 58-239) days after the first HF hospitalization. Baseline demographics, biomarker profiles, and comorbid conditions (except lower chronic kidney disease in HF rec EF ) were similar between HF rec EF and persistent reduced- EF groups. HF rec EF patients had smaller baseline left ventricular end-systolic dimension (3.6 versus 4.8 cm; P<0.01), higher baseline myocardial systolic performance (9.2% versus 8.1%; P=0.02), and improved survival (adjusted hazard ratio 0.27, 95% confidence interval 0.11, 0.62). We found a significant interaction between baseline left ventricular end-systolic dimension and absolute longitudinal strain. Among patients with left ventricular end-systolic dimension >4.35 cm, higher absolute longitudinal strain (≥8%) was associated with HF rec EF (unadjusted odds ratio=3.9, 95% CI )confidence interval 1.2, 12.8). Incorporation of baseline indices of cardiac mechanics with clinical variables resulted in a predictive model for HF rec EF with c-statistic=0.85. Conclusions Factors associated with achieving HF rec EF were specific to cardiac structure and indices of cardiac mechanics. Higher baseline absolute longitudinal strain is associated with HF rec EF among nonischemic cardiomyopathy patients with reduced EF and larger left ventricular dimensions.

Background and Objective: To describe a new approach for in-office air-fluid exchange., Patients and Methods: This manuscript describes a procedural technique. A retrospective chart review of three patients on whom the procedure was performed is presented., Results: The authors have performed this novel procedure on three eyes of three patients. All patients were followed for at least 3 months after the procedure. No short-term complications occurred, and no secondary procedures were required to achieve a near-complete air-fluid exchange., Conclusion: This novel technique is a reliable and reproducible procedure that allows for in-office air-fluid exchange with good results in this small cohort of patients. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:799-801.]., (Copyright 2018, SLACK Incorporated.)

Introduction: Inpatient telemetry monitoring is a commonly used technology designed to detect and monitor life-threatening arrhythmias. However, residents are rarely educated in the proper use and interpretation of telemetry monitoring., Methods: We developed a training module containing an educational video, PowerPoint presentation, and hands-on interactive learning session with a telemetry expert. The module highlights proper use of telemetry monitoring, recognition of telemetry artifact, and interrogation of telemetry to identify clinically significant arrhythmias. Learners completed pre- and postcurriculum knowledge-based assessments and a postcurriculum survey on their experience with the module. In total, the educational curriculum had three 60-minute sessions., Results: Thirty-two residents participated in the training module. Residents scored higher on the posttest (77% ± 12%) than on the pretest (70% ± 12%), t (31) = -4.3, p < .001. Wilcoxon signed rank tests indicated PGY-3s performed better on the posttest ( Mdn = 0.86) than on the pretest ( Mdn = 0.72), z = -2.19, p = .031. PGY-2s also performed better on the posttest ( Mdn = 0.86) than on the pretest ( Mdn = 0.76), z = -2.04, p = .042. There was no difference between pretest ( Mdn = 0.66) and posttest ( Mdn = 0.71) scores for PGY-1s, z = -1.50, p = .142. The majority of residents reported that the telemetry curriculum boosted their self-confidence, helped prepare them to analyze telemetry on their patients, and should be a required component of the residency., Discussion: This module represents a new paradigm for teaching residents how to successfully and confidently interpret and use inpatient telemetry., Competing Interests: None to report.