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Abstract: Progression of myeloproliferative neoplasms (MPNs) to accelerated or blast phase is associated with poor survival outcomes. Since 2017 there have been several therapies approved for use in acute myeloid leukemia (AML); these therapies have been incorporated into the management of accelerated/blast-phase MPNs (MPN-AP/BP). We performed a multicenter analysis to investigate outcomes of patients diagnosed with MPN-AP/BP in 2017 or later. In total, 202 patients were identified; median overall survival (OS) was 0.86 years. We also analyzed patients based on first-line treatment; the 3 most common approaches were intensive chemotherapy (n = 65), DNA methyltransferase inhibitor (DNMTi)-based regimens (n = 65), and DNMTi + venetoclax-based regimens (n = 54). Median OS was not significantly different by treatment type. In addition, we evaluated response by 2017 European LeukemiaNet AML criteria and 2012 MPN-BP criteria in an effort to understand the association of response with survival outcomes. We also analyzed outcomes in 65 patients that received allogeneic hematopoietic stem cell transplant (allo-HSCT); median OS was 2.30 years from time of allo-HSCT. Our study demonstrates that survival among patients with MPN-AP/BP is limited in the absence of allo-HSCT even in the current era of therapeutics and underscores the urgent need for new agents and approaches., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

The clinical impact of molecular ontogeny in acute myeloid leukemia (AML) was defined in patients treated with intensive chemotherapy. In a cohort of 314 newly diagnosed AML patients, we evaluated whether molecular ontogeny subgroups have differential benefit of venetoclax (VEN) added to hypomethylating agents (HMA). In secondary ontogeny (n = 115), median overall survival (OS)(14.1 vs. 6.9 months, P = 0.0054), composite complete remission (cCR 61% vs. 18%, P < 0.001) and allogeneic hematopoietic stem cell transplant (alloHCT) (24% vs. 6%, P = 0.02) rates were better in patients treated with HMA + VEN vs. HMA. In contrast, in TP53 AML(n = 111) median OS (5.7 vs. 6.1, P = 0.93), cCR (33% vs. 37%, P = 0.82) and alloHCT rates (15% vs. 8%, P = 0.38) did not differ between HMA + VEN vs. HMA. The benefit of VEN addition in the secondary group was preserved after adjustment for significant clinicopathologic variables (HR 0.59 [95% CI 0.38-0.94], P = 0.025). The OS benefit of HMA + VEN in secondary ontogeny was similar in those with vs. without splicing mutations (P = 0.92). Secondary ontogeny AML highlights a group of patients whose disease is selectively responsive to VEN added to HMA and that the addition of VEN has no clinical benefit in TP53-mutated AML., (© 2024. The Author(s).)

Molecularly defined secondary acute myeloid leukemia is associated with a prior myeloid neoplasm and confers a worse prognosis. We compared outcomes of molecularly defined secondary AML patients (n = 395) treated with daunorubicin and cytarabine (7 + 3, n = 167), liposomal daunorubicin and cytarabine (CPX-351, n = 66) or hypomethylating agents (HMA) + venetoclax (VEN) (n = 162). Median overall survival (OS) was comparable between treatment groups among patients aged >60 years. In a multivariable model HMA + VEN vs. 7 + 3 was associated with better OS (hazard ratio [HR] 0.64 [95% confidence interval (CI) 0.42-0.98, p = 0.041]), whereas CPX-351 vs. 7 + 3 was not (HR 0.79 [CI 95% 0.50-1.25, p = 0.31]). Allogeneic hematopoietic stem cell transplantation, BCOR and IDH mutations were associated with improved OS; older age, prior myeloid disease, NRAS/KRAS mutations, EZH2 mutation, and monosomal karyotype were associated with worse OS. When analyzed in each treatment separately, the IDH co-mutations benefit was seen with 7 + 3 and the detrimental effect of NRAS/KRAS co-mutations with HMA + VEN and CPX-351. In pairwise comparisons adjusted for age, HMA + VEN was associated with improved OS vs. 7 + 3 in patients with SF3B1 mutation and improved OS vs. CPX-351 in those with RNA splicing factor mutations. In molecularly defined secondary AML treatment with HMA + VEN might be preferred but could further be guided by co-mutations., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: To investigate domestic violence (DV)-related ocular injuries among adult emergency department (ED) patients in the US., Methods: This was a retrospective, cross-sectional study of patients with a diagnosis of DV and diagnosis of ocular injury in the Nationwide Emergency Department Sample (NEDS) from 2008-2017. We identified patient- and hospital-level variables associated with DV-related ocular injuries. We calculated annual incidence rates using US Census data. Adjusting for inflation using the Consumer Price Index, we calculated mean and total charges., Results: From 2008-2017, there were 26,215 ED visits for ocular injuries related to DV with an average incidence of 1.09 per 100,000 adult population (female patients, 84.5%; mean age [SE], 34.3 [0.2]). DV-related ocular injuries were most prevalent among patients in the lowest income quartile (39.1%) and on Medicaid (37.4%). Most ED visits presented to metropolitan teaching (55.4%), non-trauma (46.7%), and south regional (30.5%) hospitals. The most common ocular injury was contusion of eye/adnexa (61.1%). The hospital admission rate was 5.2% with a mean hospital stay of 2.9 [0.2]. The inflation-adjusted mean cost for medical services was $38,540 [2,310.8] per encounter with an average increase of $2,116 per encounter, annually. The likelihood of hospital admission increased for patients aged ≥60 years old, on Medicare, and with open globes or facial/orbital fractures (all p  < .05)., Conclusion: Contusion of the eye/adnexa was the most common ocular injury among patients with DV-related ED visits. To better facilitate referrals to social services, ophthalmologists should utilize DV screenings, especially towards women and patients of less privileged socioeconomic status.

Lam et al. compared trisomy acute myeloid leukaemia (AML) patients (inclusive of single trisomy, double trisomy or tetrasomy cases) with cytogenetically normal AML to uncover distinguishing molecular and prognostic features of trisomy AML. The study contributes to our understanding of trisomy AML, but the heterogeneity of trisomy subtypes remains a barrier to its study. Commentary on: Lam et al. Distinct karyotypic and mutational landscape in trisomy AML. Br J Haematol 2024;204:939-944., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Background: In the past decade, there have been significant breakthroughs in immunotherapies for B-cell lymphoid malignancies and multiple myeloma, but progress has been much less for acute myeloid leukemia (AML). Nevertheless, challenge begets innovation and several therapeutic strategies are under investigation., Summary: In this review, we review the state of the art in AML immunotherapy including CD33- and CD123-targeted agents, immune checkpoint inhibition, and adoptive cell therapy strategies. We also share conceptual frameworks for approaching the growing catalog of investigational AML immunotherapies and propose future directions for the field., Key Messages: Immunotherapies for AML face significant challenges but novel strategies are in development., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: Healthcare restrictions during the COVID-19 pandemic, particularly in ophthalmology, led to a differential underutilization of care. An analytic approach is needed to characterize pandemic health services usage across many conditions., Methods: A common analytical framework identified pandemic care utilization patterns across 261 ophthalmic diagnoses. Using a United States eye care registry, predictions of utilization expected without the pandemic were established for each diagnosis via models trained on pre-pandemic data. Pandemic effects on utilization were estimated by calculating deviations between observed and expected patient volumes from January 2020 to December 2021, with two sub-periods of focus: the hiatus (March-May 2020) and post-hiatus (June 2020-December 2021). Deviation patterns were analyzed using cluster analyses, data visualizations, and hypothesis testing., Results: Records from 44.62 million patients and 2455 practices show lasting reductions in ophthalmic care utilization, including visits for leading causes of visual impairment (age-related macular degeneration, diabetic retinopathy, cataract, glaucoma). Mean deviations among all diagnoses are 67% below expectation during the hiatus peak, and 13% post-hiatus. Less severe conditions experience greater utilization reductions, with heterogeneities across diagnosis categories and pandemic phases. Intense post-hiatus reductions occur among non-vision-threatening conditions or asymptomatic precursors of vision-threatening diseases. Many conditions with above-average post-hiatus utilization pose a risk for irreversible morbidity, such as emergent pediatric, retinal, or uveitic diseases., Conclusions: We derive high-resolution insights on pandemic care utilization in the US from high-dimensional data using an analytical framework that can be applied to study healthcare disruptions in other settings and inform efforts to pinpoint unmet clinical needs., (© 2023. The Author(s).)

Purpose: To study the epidemiology of all domestic violence (DV)-related ocular injuries among pediatric emergency department (ED) patients in the United States., Methods: This is a retrospective, cross-sectional study of isolated children (<18 years of age) with a diagnosis of DV and primary or secondary diagnosis of ocular injuries in the Nationwide Emergency Department Sample, 2008-2017. We calculated annual incidence of DV-related ocular injuries and prevalence by demographic variables, including age, sex, and income quartile. Median charges, median length of inpatient hospital stay, and factors associated with hospitalization were also measured., Results: From 2008 to 2017, there were 4,125 ED encounters, with an average incidence of 0.56 per 100,000 population (males, 50.0%; mean age [SE], 9.2 [0.3]). Patients in the lowest income quartile (42.6%) and with Medicaid insurance (63.2%) were the most prevalent. The most common known perpetrator was a family member (29.4%). Most ED encounters took place at southern regional (28.6%), metropolitan teaching (67.1%) and designated trauma hospitals (57.8%). Contusion of the eye/adnexa and being struck by or against an object were the most common ocular diagnosis and known mechanism of injury, respectively. An estimated 12.4% of patients were admitted with a median hospital stay of 4 (IQR, 2-6). Median charges during the study period were $27,415.10 (IQR, $13,142.70-$54,454.90)., Conclusions: DV-related ocular injuries were most prevalent among patients with a low socioeconomic status. Given the historical underreporting of DV, future studies are warranted to identify more specific social determinants of health that contribute to such presentations., (Copyright © 2023 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: JAK inhibition is an effective means of controlling symptom burden and improving splenomegaly in patients with myeloproliferative neoplasms (MPNs). However, a majority of patients treated with JAK inhibition will have disease progression with long-term use. In In this review, we focus on the investigation of novel targeted agents beyond JAK inhibitors both in the chronic phase of disease and in the accelerated/blast phase of disease., Recent Findings: Relevant targeted therapies in MPNs include BET inhibitors, BCL inhibitors, LSD1 inhibitors, PI3K inhibitors, IDH inhibitors, telomerase inhibitors, and MDM2 inhibitor. Agents within these classes have been investigated either as monotherapy or in combination with a JAK inhibitor. We summarize the prospective data for these agents along with detailing the ongoing phase III trials incorporating these agents. While JAK inhibition has been a mainstay of therapy in MPNs, a majority of patients will have disease of progression. JAK inhibitors also have limited anti-clonal effect and do not impact the rate of progression to the blast phase of disease. The novel therapies detailed in this review not only show promise in ameliorating the symptom burden of MPNs but may be able to alter the natural history of disease., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: In private equity (PE) buyouts of medical practices, it is common for the PE firm to raise significant levels of debt in order to finance the purchase. This debt is subsequently shouldered by the acquired practice(s). There remains a scarcity of literature quantifying the effect of PE acquisition on the subsequent financial performance of eye care practices. We aim to identify and characterize debt valuations of ophthalmology and optometry private equity-backed group (OPEG) practices, which serve as an indicator of practice financial performance., Methods: A cross-sectional study from March 2017 to March 2022 was conducted using business development company (BDC) quarterly/annual filings to the Securities and Exchange Commission (SEC). The 2021 BDC Report was used to identify all BDCs actively filing annual reports (Form 10-Ks) and quarterly reports (Form 10-Qs) in the United States in 2021. The public filings of BDCs lending to OPEGs were searched from the inception of the OPEG's debt instrument in a BDC's portfolio and the amortized cost and fair value of each debt instrument were tabulated. A panel linear regression was used to evaluate temporal changes in OPEG valuations., Results:  A total of 2,997 practice locations affiliated with 14 unique OPEGs and 17 BDCs were identified over the study period. Debt valuations of OPEGs decreased by 0.46% per quarter over the study period (95% CI: -0.88 to -0.03, P = 0.036). In the COVID-19 pre-vaccine period (March 2020 to December 2020), there was an excess (additional) 4.93% decrease in debt valuations (95% CI: -8.63 to -1.24, P = 0.010) when compared to pre-pandemic debt valuations (March 2017 to December 2019). Effects of COVID-19 on valuations stabilized during the pandemic post-vaccine period (February 2021 to March 2022), with no change in excess debt valuation compared to pre-pandemic baseline (0.60, 95% CI: -4.59 to 5.78, P = 0.822). There was an increase in practices that reported average discounted debt valuations from 20 practices (1.6%) associated with one OPEG to 1,213 practices (40.5%) associated with nine OPEGs (including 100% of newly acquired practices), despite the stabilization of COVID-19-related excess (additional) debt., Conclusions: Debt valuations of eye care practices have declined significantly post-PE investment from March 2017 to March 2022, suggesting that the financial health of these groups is volatile and vulnerable to economic contractions such as the COVID-19 pandemic. Eye care practice owners must consider long-term financial risks and impacts of subsequent patient care when selling their practice to a private equity group. Future research should assess the impact of secondary transactions of OPEGs on the financial health of practices, practitioner lifestyle, and patient outcomes., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2023, Desai et al.)

Abstract: Clonal hematopoiesis (CH) confers a high risk of aging-related diseases and hematologic malignancy. There are still significant knowledge gaps in identifying high-risk patients with CH and managing such patients. In this review, we focus on 3 areas: (1) the natural history of CH; (2) the risks of progression of CH, including CH of indeterminate potential, clonal cytopenia of undetermined significance, and therapy-related CH, to myeloid malignancy; and (3) the challenges and unmet needs of CH management and research., Competing Interests: Conflicts of Interest and Source of Funding: Z.X., E.C.C., and L.M.M. declare no conflict of interest. A.M.Z. received research funding (institutional) from Celgene/BMS, Abbvie, Astex, Pfizer, Medimmune/AstraZeneca, Boehringer-Ingelheim, Trovagene/Cardiff Oncology, Incyte, Takeda, Novartis, Aprea, and ADC Therapeutics; participated in advisory boards and/or had a consultancy with and received honoraria from AbbVie, Otsuka, Pfizer, Celgene/BMS, Jazz, Incyte, Agios, Boehringer-Ingelheim, Novartis, Acceleron, Astellas, Daiichi Sankyo, Cardinal Health, Taiho, Seattle Genetics, BeyondSpring, Cardiff Oncology, Takeda, Ionis, Amgen, Janssen, Epizyme, Syndax, Gilead, Kura, Chiesi, ALX Oncology, BioCryst, and Tyme; and served on clinical trial committees for Novartis, Abbvie, Geron, and Celgene/BMS. None of these relationships were related to this work. A.M.Z. is a Leukemia and Lymphoma Society Scholar in Clinical Research. R.K. consulted for Abbvie: speaker's bureau, advisory board; BMS: research grant, advisory board; CTI Biopharma: speaker's bureau, advisory board; Geron: consultancy; Jazz: speaker's bureau, advisory board; Novartis: advisory board; Pharma Essentia: speaker's bureau, advisory board; Servio: speaker's bureau, advisory board; Taiho: advisory board. All figures were created with BioRender.com., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Myelodysplastic syndrome (MDS) is a clonal disorder characterized by ineffective hematopoiesis and variable cytopenias with a considerable risk of progression to acute myeloid leukemia. Epidemiological assessment of MDS remains challenging because of evolving classification systems, but the overall incidence in the United States is estimated to be approximately 4 per 100,000 and increases with age. The sequential accumulation of mutations drives disease evolution from asymptomatic clonal hematopoiesis (CH) to CH of indeterminate potential, clonal cytopenia of unknown significance, to frank MDS. The molecular heterogeneity seen in MDS is highly complex and includes mutations of genes involved in splicing machinery, epigenetic regulation, differentiation, and cell signaling. Recent advances in the understanding of the molecular landscape of MDS have led to the development of improved risk assessment tools and novel therapies. Therapies targeting the underlying pathophysiology will hopefully further expand the armamentarium of MDS therapeutics, bringing us closer to a more individualized therapeutic approach based on the unique molecular profile of each patient and eventually improving the outcomes of patients with MDS. We review the epidemiology of MDS and the newly described MDS precursor conditions CH, CH of indeterminate potential, and CCUS. We then discuss central aspects of MDS pathophysiology and outline specific strategies targeting hallmarks of MDS pathophysiology, including ongoing clinical trials examining the efficacy of these therapeutic modalities., Competing Interests: Conflicts of Interest and Source of Funding: M.S. served on the advisory board for Novartis, Kymera, Sierra Oncology, GSK, and Rigel; consulted for Boston Consulting and Dedham group and participated in GME activity for Novartis, Curis Oncology, Haymarket Media, and Clinical Care Options. A.M.Z. is a Leukemia and Lymphoma Society Scholar in Clinical Research. A.M.Z. received research funding (institutional) from Celgene/BMS, Abbvie, Astex, Pfizer, Medimmune/AstraZeneca, Boehringer-Ingelheim, Cardiff Oncology, Incyte, Takeda, Novartis, Shattuck Labs, Geron, Aprea, and ADC Therapeutics. A.M.Z. participated in advisory boards and/or had a consultancy with and received honoraria from AbbVie, Pfizer, Celgene/BMS, Jazz, Incyte, Agios, Servier, Boehringer-Ingelheim, Novartis, Astellas, Daiichi Sankyo, Geron, Taiho, Seattle Genetics, BeyondSpring, Takeda, Ionis, Amgen, Janssen, Genentech, Epizyme, Syndax, Gilead, Kura, Chiesi, ALX Oncology, BioCryst, Notable, Orum, Mendus, Foran, Syros, and Tyme. A.M.Z. served on clinical trial committees for Novartis, Abbvie, Gilead, Syros, BioCryst, Abbvie, ALX Oncology, Geron, and Celgene/BMS. A.M.Z. received travel support for meetings from Pfizer, Novartis, and Cardiff Oncology. For the remaining authors, none were declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

"heel-selfie" is a method for examination and documentation of heel ulcers, particularly in patients with significant morbidity and impaired mobility. Images can be electronically saved and also be shared with caregivers., Competing Interests: None., (© 2023 The Authors.)

Purpose: Patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) have poor outcomes and require new therapies. In AML, autocrine production of hepatocyte growth factor (HGF) drives MET signaling that promotes myeloblast growth and survival, making MET an attractive therapeutic target. MET inhibition exhibits activity in AML preclinical studies, but HGF upregulation by the FGFR pathway is a common mechanism of resistance., Patients and Methods: We performed preclinical studies followed by a Phase I trial to investigate the safety and biological activity of the MET inhibitor merestinib in combination with the FGFR inhibitor LY2874455 for patients with R/R AML. Study Cohort 1 underwent a safety lead-in to determine a tolerable dose of single-agent merestinib. In Cohort 2, dose-escalation of merestinib and LY2874455 was performed following a 3+3 design. Correlative studies were conducted., Results: The primary dose-limiting toxicity (DLT) observed for merestinib alone or with LY2874455 was reversible grade 3 transaminase elevation, occurring in 2 of 16 patients. Eight patients had stable disease and one achieved complete remission (CR) without measurable residual disease. Although the MTD of combination therapy could not be determined due to drug supply discontinuation, single-agent merestinib administered at 80 mg daily was safe and biologically active. Correlative studies showed therapeutic plasma levels of merestinib, on-target attenuation of MET signaling in leukemic blood, and increased HGF expression in bone marrow aspirate samples of refractory disease., Conclusions: We provide prospective, preliminary evidence that MET and FGFR are biologically active and safely targetable pathways in AML., (©2022 American Association for Cancer Research.)

Background: Perioperative services contribute up to 70% of the US hospitals' solid waste generation. While surgical textiles are more environmentally friendly than their disposable counterparts, many US institutions have converted to disposable surgical wear in the last few decades. End-users' perception surrounding reusable textiles is currently unknown., Methods: Perioperative staff at the University of California San Francisco (UCSF) were surveyed to assess perceptions of reusable surgical gowns to guide potential implementation. The instrument included eight close-ended questions drawn from prior studies and a free-response section. The survey was piloted before dissemination. Descriptive statistics and qualitative inductive theme analysis were applied., Results: 205 participants or 19.8% of the workforce responded. 77.6% perceived reusable surgical gowns as better for the environment, while 34.1% were unsure or believed that switching to reusable surgical gowns would increase surgical site infections. If given an option, 39.8% preferred reusable gowns, 30.7% preferred disposable gowns, and 25.4% had no preference. Qualitatively, four themes were identified concerning reusable gowns' 1) functionality and safety, 2) user comfort, 3) environmental concern, and 4) cost, which hindered end-user buy-in. Laundering water utilization in a drought-prone area was of particular concern., Conclusions: While most perioperative staff in a US tertiary hospital believed reusable surgical gowns were environmentally friendly, ambivalence towards transitioning to reusable gowns stemmed from uncertainty in reusable textiles' environmental benefits, safety profile, and cost savings. These perceptions may prevent successful implementation of reusable surgical gowns and suggest a need for staff education and context-specific environmental impact analyses., Key Message: End-user perceptions on transitioning to reusable surgical gowns are mixed and revolve around uncertainty in their environmental benefits, cost, and functionality, which may hinder their successful implementation., Competing Interests: The authors do not have any relevant conflicts of interest to disclose. The authors report no proprietary or commercial interest in any product mentioned or concept discussed in this article., (© 2022 The Authors.)

Context: Adult depression treatment in primary care is improved by integrated behavioral health such as the Collaborative Care Model (CoCM) but outcomes vary across health centers. Objective: Identify CoCM team factors associated with variation in clinical outcomes. Study Design: Correlative study of survey with linked clinical data from routine care. Setting or Dataset: Primary care health centers in Washington state participating in two CoCM implementation and sustainment initiatives (MHIP and BHIP). Clinical data from the Care Management Tracking System (CMTS) used as part of routine clinical care in all sites. Population studied: CoCM clinical teams and adults diagnosed with depression and receiving care from 31 distinct clinic sites throughout Washington state. Instrument: A survey for CoCM Care Managers was developed based on qualitative work exploring CoCM team function in eight domains: overall team function (OTF), psychiatric consultant (PsyC), relationship with primary care physicians (RPCP), role in the practice (RP), training experience (TE), thoughts on CoCM (TOC), leadership support (LS), and overall experience with CoCM (EXP). Outcome Measures: Depression symptoms (PHQ-9) measured as part of regular clinical care. Clinically significant improvements were defined as ≥50% improvement, last PHQ-9 measured <10, and a last PHQ-9 measured <5 (remission). Results: Data from 59 Care Manager surveys and 2509 patients from 31 clinics showed psychometric evidence for the 8 survey domains. Unadjusted multilevel mixed-effects logistic regression found the PsyC domain was associated (p<0.05) with >50% change in PHQ-9 (OR=1.32, p=0.046), last PHQ-9 <10 (OR=1.34, p=0.009), and last PHQ-9 <5 (OR=1.25, p=0.029). Adjusting simultaneously for both clinic-level and patient-level variables, the PsyC domain was significantly associated with likelihood of patient remission (last PHQ-9 <5; OR=1.22, p=0.031). Conclusions: An instrument to assess perceived functioning of the CoCM team had psychometric support. Perceived characteristics of psychiatric consultants was associated with likelihood of depression remission. Characteristics included interest in teaching, commitment to the site, making efforts to have weekly meetings, and willingness to assist care managers on adjustment of treatment strategies. This study is the first to quantify variation in CoCM team functioning with patient outcomes and can be used to inform training and the use of the CoCM., Competing Interests: None, (© 2021 Annals of Family Medicine, Inc.)

Background: Subacute combined degeneration (SCD) is a rare complication of chronic vitamin B12 deficiency that presents with a variety of neurologic findings, including decreased sensation in the extremities, increased falls, and visual changes. Treatment of SCD involves prompt replacement of vitamin B12 and addressing the underlying conditions that cause the deficiency. Given the prevalence of B12 deficiency in the older adult population, clinicians should remain alert to its possibility in patients who present with progressive neuropathy., Case Presentation: This report presents a case of a patient with progressive SCD secondary to chronic B12 deficiency despite monthly intramuscular B12 injections., Conclusions: Appropriate B12 replacement is aggressive and involves intramuscular B12 1000 mcg every other day for 2 to 3 weeks, followed by additional IM administration every 2 months before transitioning to oral therapy. Failure to adequately replenish B12 can lead to progression or lack of resolution of SCD symptoms., Competing Interests: Author disclosures The authors report no actual or potential conflicts of interest and no outside source of funding with regard to this article., (Copyright © 2022 Frontline Medical Communications Inc., Parsippany, NJ, USA.)

Purpose: To identify disparities in the use of telemedicine during the coronavirus disease 2019 (COVID-19) pandemic., Design: A cross-sectional study of completed clinical encounters in an academic ophthalmology center from March 2020 through August 2020., Participants: A total of 5023 patients comprising 8116 ophthalmic clinical encounters., Methods: Medical charts were abstracted for demographic information. We identified zip code-level socioeconomic characteristics, which were drawn from the 2019 American Community Survey 5-year estimates., Main Outcome Measures: The completion of a synchronous video encounter, the completion of a telephone (audio-only) encounter in the absence of any video encounters, or the completion of in-person encounters only., Results: During the study period, 8116 total clinical encounters were completed for 5023 unique patients. Of these patients, 446 (8.9%) participated in a video encounter, 642 (12.8%) completed a telephone encounter, and 3935 (78.3%) attended clinical appointments in person only. In adjusted analysis, patients who were Black (odds ratio [OR], 0.65; 95% confidence interval [CI], 0.52-0.80; P < 0.001) or Hispanic/Latino (OR, 0.65; 95% CI, 0.49-0.85; P = 0.002) were significantly less likely to complete a video or telephone appointment. Older patients (OR, 0.99; 95% CI, 0.98-0.99; P < 0.001), patients whose primary language was not English (OR, 0.49; 95% CI, 0.28-0.82; P = 0.01), Black patients (OR, 0.45; 95% CI, 0.32-0.62; P < 0.001), and Hispanic/Latino patients (OR, 0.56; 95% CI, 0.37-0.83; P = 0.005) were significantly less likely to complete a video encounter. Finally, among patients completing any type of telemedicine encounter, older age, (OR, 1.02; 95% CI, 1.01-1.03; P < 0.001), Medicare insurance (OR, 1.55; 95% CI, 1.11-2.17; P = 0.01), and Black race (OR, 1.97; 95% CI, 1.33-2.94; P < 0.001) were associated with using only phone visits., Conclusions: Ethnic/racial minorities, older patients, and non-English-speaking individuals were significantly less likely to complete a video telehealth encounter. With the expansion of telemedicine and the need to reduce the disparate impact of COVID-19 on minorities, it will be increasingly important to identify barriers to telehealth use and opportunities to improve access., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Disease relapse after hematopoietic cell transplantation (HCT) is a major cause of treatment failure for patients with acute myeloid leukemia (AML). Maintenance therapy after HCT for patients with targetable mutations such as mutated IDH1 or IDH2 may improve outcomes, and clinical trials evaluating this strategy are ongoing. However, clinical outcomes of IDH1- and IDH2-mutated AML patients after HCT have not been well described. The primary objective of this study was to describe the clinical characteristics and post-HCT outcomes of IDH-mutated AML patients. Survival outcomes included progression-free survival (PFS), overall survival, and cumulative incidences of relapse and nonrelapse mortality. In this multicenter retrospective analysis, 112 adult patients with IDH1- or IDH2-mutated AML who underwent HCT and did not receive an IDH inhibitor as maintenance therapy after HCT were identified at Massachusetts General Hospital, Dana Farber Cancer Institute, and Ohio State University. Mutation testing was performed using next-generation sequencing panels. Patient characteristics were collected retrospectively, and their survival outcomes were analyzed. Univariate and multivariate analyses were performed. The median patient age was 64.1 years. The median follow-up was 27.5 months. Among patients, 78.5% had intermediate- or adverse-risk disease by European LeukemiaNET criteria. Fifty-eight percent of patients received intensive induction chemotherapy, 82% of patients underwent HCT during first complete remission (CR) or CR with incomplete hematologic recovery (CRi), and 34% of patients received myeloablative conditioning. Frequently detected co-mutations were DNMT3A (35.7%), NPM1 (33.1%), and FLT3-ITD (13.4%); TP53 mutations were detected in 3.6% of patients. For IDH1-mutated patients transplanted during first CR/CRi, the 1- and 2-year PFS was 75% and 58%, respectively. For IDH2-mutated patients transplanted in first CR/CRi, the 1- and 2-year PFS was 64% and 58%, respectively. The 2-year cumulative incidence of relapse was 31% and 25% for IDH1- and IDH2-mutated cohorts, respectively. Multivariable analysis suggested first CR/CRi and age ≤60 was associated with improved outcomes for IDH2-mutated patients. To date, this is the largest multicenter study of outcomes of IDH-mutated AML patients after HCT. Our analysis provides important benchmarks for analysis and interpretation of results emerging from clinical trials evaluating maintenance IDH1 and IDH2 inhibitor therapy for AML patients after HCT., (Copyright © 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Purpose: To describe follow-up rates for patients referred for outpatient ophthalmic care after emergency department (ED) discharge and identify patient and visit characteristics associated with loss to follow-up (LTFU)., Design: Single-institution retrospective cohort study., Methods: We analyzed the medical records of 2,206 patients seen in the ED for an eye-related issue who were subsequently scheduled for ophthalmology follow-up between 2013 and 2019 at a single tertiary health system. The main outcome measures were the frequency of and risk factors for LTFU and ED revisits., Results: In total, 1,649 (74.8%) patients completed follow-up within 2 months of an index ED visit. In multivariable analysis, younger age (P < .001), a nonurgent ophthalmic condition or nonophthalmic primary diagnosis (P < .001), scheduled follow-up >5 days after the ED visit (P < .001), additional follow-up appointments (<.001), no prior history of ophthalmology appointments (P = .045), a visual acuity of 20/40 or better (P = .027), and having Medicaid or being uninsured (P < .001) were significantly associated with LTFU. The presence of an interpreter significantly increased the likelihood of follow-up among non-English speaking patients (P < .001). LTFU was significantly associated with an ED revisit within 4 months of an index visit, and the ED revisit rate was significantly higher for patients LTFU vs those who completed follow-up (5.7% vs 1.1%; P < .001)., Conclusions: A quarter of patients referred for ophthalmic care after an ED presentation were LTFU. We identified numerous factors associated with LTFU that could be used to develop interventions to enhance follow-up. In addition, patients who were LTFU were more likely to revisit the ED for the same ophthalmic condition., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To characterize the rates of panretinal photocoagulation (PRP) and anti-vascular endothelial growth factor (VEGF) medications before and after publication of the Diabetic Retinopathy Clinical Research Network protocol S., Design: A retrospective, cross-sectional study from January 2012, through September 2019, using a nationally representative claims-based database, Clinformatics Data Mart Database (OptumInsight, Eden Prairie, MN)., Participants: Eyes newly diagnosed with proliferative diabetic retinopathy (PDR), continuous enrollment, and no prior treatment with PRP or anti-VEGF agents., Methods: Interrupted time series regression analysis was performed to identify the annual change in treatment rates before and after the publication of Protocol S (November 2015)., Main Outcome Measures: Annual rates of anti-VEGF or PRP treatments per 1000 treated eyes with PDR., Results: From 2012 through 2019, 10 035 PRP or anti-VEGF treatments were administered to 3685 PDR eyes. Of these, 63.6% (n = 6379) were anti-VEGF agents, and 36.4% (n = 3656) were PRP treatments. Throughout treatment, 88.7% of eyes treated with anti-VEGF received the same agent and 7.7% were treated with both PRP and anti-VEGF agents. Panretinal photocoagulation rates declined from 784/1000 treated eyes in 2012 to 566/1000 in 2019 (pre-Protocol S: β = -32 vs. post-Protocol S: -77; P = 0.005), whereas anti-VEGF rates increased from 876/1000 in 2012 to 1583/1000 in 2019 (β = -48 vs. 161, respectively; P = 0.001). Panretinal photocoagulation rates in diabetic macular edema (DME) eyes did not significantly differ from 474/1000 in 2012 to 363/1000 in 2019 (β = -9 vs. -58 respectively; P = 0.091), and anti-VEGF rates increased from 1533/1000 in 2012 to 2096/1000 in 2019 (β = -57 vs. 187; P = 0.043). In eyes without DME, PRP use declined from 1017/1000 in 2012 to 707/1000 in 2019 (β = -31 vs. -111, respectively; P < 0.001), and anti-VEGF use increased from 383/1000 in 2012 to 1226/1000 in 2019 (β = -48 vs. 140, respectively; P < 0.001)., Conclusions: Following the publication of Protocol S, PRP rates decreased, while anti-VEGF rates increased. Panretinal photocoagulation rates did not significantly change among eyes with DME. Our findings indicate the impact that randomized controlled trials can have on real-world practice patterns., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Congenital anomalies of the kidney and urinary tract (CAKUT) constitute one of the most frequent birth defects and represent the most common cause of chronic kidney disease in the first three decades of life. Despite the discovery of dozens of monogenic causes of CAKUT, most pathogenic pathways remain elusive. We performed whole-exome sequencing (WES) in 551 individuals with CAKUT and identified a heterozygous de novo stop-gain variant in ZMYM2 in two different families with CAKUT. Through collaboration, we identified in total 14 different heterozygous loss-of-function mutations in ZMYM2 in 15 unrelated families. Most mutations occurred de novo, indicating possible interference with reproductive function. Human disease features are replicated in X. tropicalis larvae with morpholino knockdowns, in which expression of truncated ZMYM2 proteins, based on individual mutations, failed to rescue renal and craniofacial defects. Moreover, heterozygous Zmym2-deficient mice recapitulated features of CAKUT with high penetrance. The ZMYM2 protein is a component of a transcriptional corepressor complex recently linked to the silencing of developmentally regulated endogenous retrovirus elements. Using protein-protein interaction assays, we show that ZMYM2 interacts with additional epigenetic silencing complexes, as well as confirming that it binds to FOXP1, a transcription factor that has also been linked to CAKUT. In summary, our findings establish that loss-of-function mutations of ZMYM2, and potentially that of other proteins in its interactome, as causes of human CAKUT, offering new routes for studying the pathogenesis of the disorder., (Copyright © 2020 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Purpose: To estimate temporal trends in total and out-of-pocket (OOP) expenditures for ophthalmic prescription medications among adults in the United States., Design: Retrospective, longitudinal cohort study., Participants: Participants in the 2007 through 2016 Medical Expenditure Panel Survey (MEPS) 18 years of age or older. The MEPS is a nationally representative survey of the noninstitutionalized, civilian United States population., Methods: We estimated trends in national and per capita annual ophthalmic prescription expenditures by pooling data into 2-year cycles and using weighted linear regressions. We also identified characteristics associated with greater total or OOP expenditures with multivariate weighted linear regression. Costs were adjusted to 2016 United States dollars using the gross domestic product price index., Main Outcome Measures: Trends in total and OOP annual expenditures for ophthalmic medications from 2007 through 2016 as well as factors associated with greater expenditures., Results: From 2007 through 2016, 9989 MEPS participants (4.2%) reported ophthalmic medication prescription use. Annual ophthalmic medication use increased from 10.0 to 12.2 million individuals from 2007 and 2008 through 2015 and 2016. In this same period, national expenditures for ophthalmic medications increased from $3.39 billion to $6.08 billion and OOP expenditures decreased from $1.34 to $1.18 billion. Per capita expenditure increased from $338.72 to $499.42 (P < 0.001), and per capita OOP expenditure decreased from $133.48 to $96.67 (P < 0.001) from 2007 and 2008 through 2015 and 2016, respectively. From 2015 through 2016, dry eye (29.5%) and glaucoma (42.7%) medications accounted for 72.2% of all ophthalmic medication expenditures. Patients who were older than 65 years (P < 0.001), uninsured (P < 0.001), and visually impaired (P < 0.001) were significantly more likely to have greater OOP spending on ophthalmic medications., Conclusions: Total ophthalmic medication expenditure in the United States increased significantly over the last decade, whereas OOP expenses decreased. Increases in coverage, copayment assistance, and use of expensive brand drugs may be contributing to these trends. Policy makers and physicians should be aware that rising overall drug expenditures ultimately may increase indirect costs to the patient and offset a decline in OOP prescription drug spending., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Despite the widespread implementation of public health measures, coronavirus disease 2019 (COVID-19) continues to spread in the United States. To facilitate an agile response to the pandemic, we developed How We Feel, a web and mobile application that collects longitudinal self-reported survey responses on health, behaviour and demographics. Here, we report results from over 500,000 users in the United States from 2 April 2020 to 12 May 2020. We show that self-reported surveys can be used to build predictive models to identify likely COVID-19-positive individuals. We find evidence among our users for asymptomatic or presymptomatic presentation; show a variety of exposure, occupational and demographic risk factors for COVID-19 beyond symptoms; reveal factors for which users have been SARS-CoV-2 PCR tested; and highlight the temporal dynamics of symptoms and self-isolation behaviour. These results highlight the utility of collecting a diverse set of symptomatic, demographic, exposure and behavioural self-reported data to fight the COVID-19 pandemic.

Purpose: To evaluate the association between Medicaid expansion and diabetic dilated eye examinations., Design: A retrospective difference in differences (DiD) analysis using individual-level survey response data from January 1, 2009, to December 31, 2017., Participants: A total of 52 392 survey responses from 50 states and the District of Columbia between 2009 and 2017. Responders were adults aged 18 to 64 years reporting a previous diagnosis of diabetes and a household income below 138% of the US federal poverty line (FPL)., Methods: The Centers for Disease Control and Prevention's Behavioral Risk Factor Surveillance System data were used to identify survey responders who were asked about the presence of dilated eye examinations from years before and after Medicaid expansion implementation., Main Outcome Measures: The DiD in proportion of dilated eye examinations among diabetic persons aged 18 to 64 years with household incomes below 138% of the FPL between states that did and did not implement Medicaid expansion., Results: Implementation of Medicaid expansion policies was associated with a 1.3% (95% confidence interval [CI], -3.8 to 6.4; P = 0.61), 6.3% (95% CI, 1.3-11.3; P = 0.016), 4.1% (95% CI, -0.8 to 9.0; P = 0.11), and 2.3% (95% CI, -1.6 to 6.2; P = 0.23) increase in the proportion of diabetic persons aged 18 to 64 years with incomes below 138% of the FPL receiving a dilated eye examination within the past year due to Medicaid expansion 1, 2, 3, and 4 cumulative years after expansion, respectively., Conclusions: Medicaid expansion policies were significantly associated with an increase in dilated eye examination rates within the first 2 years after implementation. However, this increase did not persist beyond this period, with nonsignificant increases 3 and 4 cumulative years after implementation. Healthcare policymakers should be aware that additional measures beyond expanding insurance coverage may be necessary to increase and sustain the rate of dilated eye examinations among diabetic populations., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To identify temporal and geographic trends in private equity (PE)-backed acquisitions of ophthalmology and optometry practices in the United States., Design: A cross-sectional study using private equity acquisition and investment data from January 1, 2012, through October 20, 2019., Participants: A total of 228 PE acquisitions of ophthalmology and optometry practices in the United States between 2012 and 2019., Methods: Acquisition and financial investment data were compiled from 6 financial databases, 4 industry news outlets, and publicly available press releases from PE firms or platform companies., Main Outcome Measures: Yearly trends in ophthalmology and optometry acquisitions, including number of total acquisitions, clinical locations, and providers of acquired practices as well as subsequent sales, median holding period, geographic footprint, and financing status of each platform company., Results: A total of 228 practices associated with 1466 clinical locations and 2146 ophthalmologists or optometrists were acquired by 29 PE-backed platform companies. Of these acquisitions, 127, 9, and 92 were comprehensive or multispecialty, retina, and optometry practices, respectively. Acquisitions increased rapidly between 2012 and 2019: 42 practices were acquired between 2012 and 2016 compared to 186 from 2017 through 2019. Financing rounds of platform companies paralleled temporal acquisition trends. Three platform companies, comprising 60% of platforms formed before 2016, were subsequently sold or recapitalized to new PE investors by the end of this study period with a median holding period of 3.5 years. In terms of geographic distribution, acquisitions occurred in 40 states with most PE firms developing multistate platform companies. New York and California were the 2 states with the greatest number of PE acquisitions with 22 and 19, respectively., Conclusions: Private equity-backed acquisitions of ophthalmology and optometry practices have increased rapidly since 2012, with some platform companies having already been sold or recapitalized to new investors. Additionally, private equity-backed platform companies have developed both regionally focused and multistate models of add-on acquisitions. Future research should assess the impact of PE investment on patient, provider, and practice metrics, including health outcomes, expenditures, procedural volume, and staff employment., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

The use of all-trans retinoic acid (ATRA) combined with arsenic trioxide (ATO) with or without cytotoxic chemotherapy is highly effective in acute promyelocytic leukemia (APL) but incident chronic adverse events (AEs) after initiation of therapy are not well understood. We retrospectively analyzed adult patients with newly diagnosed APL from 2004 through 2014 to identify incident AEs following treatment and contributing risk factors. Cardiac and neurologic AEs were more common and characterized in detail. Cardiac AEs such as the development of coronary artery disease (CAD), arrhythmias, and heart failure had a cumulative incidence of 6.4% (CI95 1.8-11.1%), 2.9% (CI95 0.0-6.4%), 5.8% (CI95 1.2-10.3%) at 4 years from diagnosis, respectively. In multivariate analyses of factors influencing heart failure, the presence of clinical or radiographic CAD (HR 4.25; P  = 0.011) or troponin elevation prior to completion of therapy (HR 8.86; P  = 0.0018) were associated with increased heart failure incidence, but not anthracycline use or dose. Neurological AEs were common following therapy; at 4 years, the cumulative incidence of vision changes was 12.4% (CI95 6.0-18.7%), peripheral neuropathy 10.3% (CI95 4.5-16.1%), and memory or cognitive change 7.6% (CI95 2.5-12.7%). We did not identify any association between specific therapies and the development of cardiac and neurologic AEs. APL is a highly curable leukemia; further efforts are needed to address incident chronic AEs, with particular focus on cardiac and neurological care.