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Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative option for high-risk myeloid malignancies. Post-transplant cyclophosphamide (PT-Cy) has proven to be effective for graft versus host disease (GVHD) prophylaxis. Given that graft-versus-tumor (GVT) effect plays a major role in reducing the risk of disease relapse, the application of PT-Cy must balance the risk of relapse. Mixed chimerism (MC) refers to a state of concurrent presence of recipient and donor cells post allo-HSCT which may precede relapse disease., Objective: We investigated the impact of PT-Cy on early MC (EMC) and disease relapse in patients with a myeloid malignancy post allo-HSCT., Study Design: This retrospective single-center study included patients that underwent allo-HSCT between 2015 and 2021. Patient and disease characteristics were collected from the electronic health records. EMC was defined as <95% donor cells at day 90-120 post allo-HSCT., Results: A total of 144 patient that received an allo-HSCT were included in the study. One hundred and eight (75%) patients received PT-Cy as part of the GVHD prophylaxis regimen. The majority underwent allo-HSCT for acute myeloid leukemia (62%) or myelodysplastic syndrome (31%). Sixty-five percent received allo-HSCT from a matched unrelated donor transplant and 65% received a myeloablative conditioning regimen. A lower rate of chronic GVHD (p = 0.03) and a higher rate of EMC (p = 0.04) were observed in patients that received PT-Cy. PT-Cy was not associated with overall survival (OS) and relapse-free survival (RFS). Multivariable analysis identified measurable residual disease status (p = 0.003), hematopoietic cell transplantation-specific comorbidity index (p = 0.012) and chronic GVHD (p = 0.006) as independent prognostic variables for OS. AML-adverse risk (p = 0.004) and EMC (p = 0.018) were independently prognostic for RFS. While EMC overall was not significantly associated with higher risk of relapse, EMC was associated with shorter RFS within adverse-risk AML patients., Conclusion: Our study shows that PT-Cy was associated with an increased risk of EMC. The predictive value of EMC for relapse remains unclear and may depend on the underlying disease, which should be validated in a larger cohort., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: Patients diagnosed with hematologic malignancies are at increased risk for severe SARS-CoV-2 infection. We evaluated the serological IgG response following two doses of the SARS-CoV-2 vaccine in patients with hematologic malignancies., Methods: Patients treated at UT Southwestern Medical Center with a diagnosis of a myeloid or lymphoid neoplasm were included. SARS-CoV-2 vaccination response was defined as a positive quantifiable spike IgG antibody titer., Results: Sixty patients were included in the study and 60% were diagnosed with a myeloid neoplasm. The majority (85%) of the patients with a myeloid malignancy and 50% of the patients with a lymphoid malignancy mounted a serological response after receiving two doses of the vaccine., Conclusion: Vaccination should be offered irrespective of ongoing treatment or active disease. Findings require validation in a larger cohort of patients., (Copyright © Hoff et al. This article is available under a Creative Commons License (Attribution 4.0 International).)

Angiomatoid fibrous histiocytoma (AFH) is a soft tissue neoplasm of intermediate biological potential. Typically a slow-growing tumor, it can recur locally. Rarely, it manifests as a soft tissue sarcoma capable of metastasis. When metastases are nonamenable to local therapy, it is believed uniformly fatal. We present 3 patients with metastatic AFH who demonstrated a sustained response to chemotherapy; including one who achieved complete remission with cryoablation. These cases reinforce the potential value of chemotherapy in some patients with unresectable metastatic AFH and provide the first case in the literature of cryoablation in AFH., Competing Interests: J. C. Chisholm (through The Giant Pledge) and E. Pace are supported by The Royal Marsden Cancer Charity. The remaining authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Hepatocellular carcinoma (HCC) remains a deadly disease, with patients' best hope for a cure being liver transplantation; however, access to health care resources, such as donor organs, between ethnic groups has historically been unbalanced. Ensuring equitable access to donor livers is crucial to minimize disparities in HCC outcomes. As a result, we sought to better elucidate the differences in transplantation rates among various ethnic groups., Materials and Methods: The National Inpatient Sample (NIS) was utilized to evaluate for disparities in liver transplantation in patients whose primary or secondary diagnosis was recorded as HCC or hepatoma. The study included admissions between 2007 and 2014 to centers with at least 1 documented liver transplant., Results: A total of 7244 transplants were performed over 70,406 weighted admissions. Black race was associated with lower transplantation rates, with an adjusted odds ratio of 0.46 (95% confidence interval: 0.42-0.51, P <0.01) when accounting for a number of possible confounders including socioeconomic and geographic factors., Conclusions: Our study observed decreased rates of liver transplant in blacks compared with whites for HCC. Furthermore, improved economic status and private insurance had a significantly higher odds ratio for transplantation. Hospital-level studies are needed to clarify confounding factors not apparent in large administrative datasets and help better investigate factors that lead to less optimal transplant rates among blacks. Interventions may include more optimal screening policies and procedures, improved interdisciplinary management, and earlier referrals., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

T-type calcium (Ca V 3) channels are involved in cardiac automaticity, development, and excitation-contraction coupling in normal cardiac myocytes. Their functional role becomes more pronounced in the process of pathological cardiac hypertrophy and heart failure. Currently, no Ca V 3 channel inhibitors are used in clinical settings. To identify novel T-type calcium channel ligands, purpurealidin analogs were electrophysiologically investigated. These compounds are alkaloids produced as secondary metabolites by marine sponges, and they exhibit a broad range of biological activities. In this study, we identified the inhibitory effect of purpurealidin I (1) on the rat Ca V 3.1 channel and conducted structure-activity relationship studies by characterizing the interaction of 119 purpurealidin analogs. Next, the mechanism of action of the four most potent analogs was investigated. Analogs 74 , 76 , 79 , and 99 showed a potent inhibition on the Ca V 3.1 channel with IC 50 's at approximately 3 μM. No shift of the activation curve could be observed, suggesting that these compounds act like a pore blocker obstructing the ion flow by binding in the pore region of the Ca V 3.1 channel. A selectivity screening showed that these analogs are also active on hERG channels. Collectively, a new class of Ca V 3 channel inhibitors has been discovered and the structure-function studies provide new insights into the synthetic design of drugs and the mechanism of interaction with T-type Ca V channels.

A cancerous tumour termed hepatocellular carcinoma (HCC) is characterized by inflammation and subsequently followed by end-stage liver disease and necrosis of the liver. The liver's continuous exposure to microorganisms and toxic molecules affects the immune response because normal tissue requires some immune tolerance to be safeguarded from damage. Several innate immune cells are involved in this process of immune system activation which includes dendritic cells, macrophages, and natural killer cells. The liver is an immunologic organ with vast quantities of innate and innate-like immune cells subjected to several antigens (bacteria, fungal or viral) through the gut-liver axis. Tumour-induced immune system engagement may be encouraged or suppressed through innate immunological systems, which are recognized promoters of liver disease development in pre-HCC conditions such as fibrosis or cirrhosis, ultimately resulting in HCC. Immune-based treatments containing several classes of drugs have transformed the treatment of several types of cancers in recent times. The effectiveness of such immunotherapies relies on intricate interactions between lymphocytes, tumour cells, and neighbouring cells. Even though immunotherapy therapy has already reported to possess potential effect to treat HCC, a clear understanding of the crosstalk between innate and adaptive immune cell pathways still need to be clearly understood for better exploitation of the same. The identification of predictive biomarkers, understanding the progression of the disease, and the invention of more efficient combinational treatments are the major challenges in HCC immunotherapy. The functions and therapeutic significance of innate immune cells, which have been widely implicated in HCC, in addition to the interplay between innate and adaptive immune responses during the pathogenesis, have been explored in the current review., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

As online media acquires increased utilization as a means of disseminating scientific research, Altmetric analyses are useful to identify socially impactful publications and their characteristics. Accordingly, the objective of this investigation was to determine the most mentioned articles online regarding craniofacial surgery and compare these articles with their most cited counterparts. Using the Web of Science database, 7097 craniofacial surgery publications were identified. Altmetric Attention Score (AAS) and average citations per year (ACpY) were extracted, and articles were ranked by their social and scientific impact. Descriptive, comparative, and correlational analyses were performed to examine characteristics including AAS, ACpY, country of origin, journal, open access (OA) status, publication year, study design, and topic. The average AAS of the 50 most mentioned articles was 83.68 (SD±107.40), and the average citation count of the 50 most cited articles was 76.38 (SD±35.15). OA status was significantly more prevalent among the most mentioned articles (24.0%) relative to all articles (10.72%) and the most cited articles (4.0%). The most mentioned and the most cited articles primarily originated from the United States (64.0% and 38.0%, respectively), discussed topics related to the medical and surgical management of patients (48.0% and 58.0%, respectively), and were systematic reviews (16.0% and 28.0%, respectively). However, there was significantly more geographic diversity in the latter cohort. In summary, this comparative examination reveals important differences between the most mentioned and most cited articles, highlighting the distinct utility of AAS and citation count when evaluating research impact., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 by Mutaz B. Habal, MD.)

Objectives: A contributing factor to unsuccessful prenatal spina bifida aperta (SBA) repair via an open approach may be incomplete neurosurgical repair causing persistent in-utero leakage of cerebrospinal fluid (CSF) and exposure of the fetal spinal cord to amniotic fluid. We aimed to investigate the neurostructural and neurofunctional efficacy of watertight prenatal SBA repair in a validated SBA fetal lamb model., Methods: A well-powered superiority study was conducted in the validated SBA fetal lamb model (n = 7 per group). The outcomes of lambs which underwent watertight or non-watertight multilayer repair through an open approach were compared to those of unrepaired SBA lambs (historical controls) at delivery (term = 145 days). At ∼75 days, fetal lambs underwent standardized induction of lumbar SBA. At ∼100 days, they were assigned to an either watertight or non-watertight layered repair group based on an intraoperative watertightness test using subcutaneous fluorescein injection. At 1-2 days postnatally, as primary outcome, we assessed reversal of hindbrain herniation using magnetic resonance imaging (MRI). Secondary proxies of neuroprotection were: absence of CSF leakage at the repair site; hindlimb motor function based on joint-movement score, locomotor grade and Motor Evoked Potential (MEP); four-score neuroprotection scale, encompassing live birth, complete hindbrain herniation reversal, absence of CSF leakage and joint-movement score ≥ 9/15; and brain and spinal cord histology and immunohistochemistry. As the watertightness test cannot be used clinically due to its invasiveness, we developed a potential surrogate intraoperative three-score skin-repair-quality scale based on visual assessment of the quality of the skin repair (suture inter-run distance ≤ 3 mm, absence of tear and absence of ischemia), with high quality defined by a score ≥ 2/3 and low quality by a score < 2/3, and assessed its relationship with improved outcome., Results: Compared with unrepaired lambs, lambs with watertight repair achieved a high level of neuroprotection (neuroprotection score of 4/4 in 5/7 vs 0/7 lambs) as evidenced by: a significant 100% (vs 14%) reversal of hindbrain herniation on MRI; low CSF leakage (14% vs 100%); better hindlimb motor function, with higher joint-movement score, locomotor grade and MEP area under the curve and peak-to-peak amplitude; higher neuronal density in the hippocampus and corpus callosum; and higher reactive astrogliosis at the SBA lesion epicenter. Conversely, lambs with non-watertight SBA repair did not achieve the same level of neuroprotection (score of 4/4 in 1/7 lambs) compared with unrepaired lambs, with: a non-significant 86% (vs 14%) reversal of hindbrain herniation; high CSF leakage (43% vs 100%); no improvement in motor function; low brain neuron count in both the hippocampus and corpus callosum; and small spinal astroglial cell area at the epicenter. Both watertight layered repair and high (≥ 2/3) intraoperative skin-repair-quality score were associated with improved outcome, but the watertightness test and skin-repair-quality scale could not be used interchangeably due to result discrepancies., Conclusions: Watertight layered fetal SBA repair is neuroprotective since it improves brain and spinal-cord structure and function in the fetal lamb model. This translational research has important clinical implications. A neurosurgical technique that achieves watertightness should be adopted in all fetal centers to improve neuroprotection. Future clinical studies could assess whether a high skin-repair-quality score (≥ 2/3) correlates with neuroprotection. © 2022 International Society of Ultrasound in Obstetrics and Gynecology., (© 2022 International Society of Ultrasound in Obstetrics and Gynecology.)

Purpose: Glaucoma is a worldwide leading cause of irreversible blindness. Standard treatments lower intraocular pressure (IOP). Novel treatments to prevent optic nerve (ON) degeneration are needed. Here, we investigate the hypothesis that sigma-1 receptor (S1R) agonist (+)-pentazocine (PTZ) is neuroprotective in a Brown Norway (BN) rat, microbead model of glaucoma., Methods: BN rats (9-11 weeks, male and female) were treated by intraperitoneal injection, 3 times per week with (+)-PTZ (2 mg/kg) or vehicle (VEH) alone. Treatment started 1 week prior to intraocular injection of polystyrene microbeads to elevate IOP. IOP was measured 2-3 times per week. Five weeks post microbead injection, rats were euthanized. ONs were removed, then fixed and processed for 63x oil, light microscope imaging of toluidine blue stained ON cross sections. To facilitate comparison of ON morphology from VEH and (+)-PTZ treated rats with similar ocular hypertensive insults, rats were assigned to low (IOP ≤15.8 mmHg), moderate (15.8 < IOP <28.0 mmHg), and high (IOP ≥28.0 mmHg) groups based on average IOP in the microbead injected eye. Axon numbers, axon density, axonal and glial areas, axon loss, and axon size distributions of naïve, bead, and contralateral ONs were assessed using QuPath program for automated image analysis., Results: (+)-PTZ treatment of BN rats protected ONs from damage caused by moderate IOP elevation. Treatment with (+)-PTZ significantly reduced axon loss and glial areas, and increased axon density and axonal areas compared to ONs from VEH treated rats with moderate IOP. (+)-PTZ-mediated neuroprotection was independent of IOP lowering effects. At average IOP ≥28.0 mmHg, (+)-PTZ treatment did not provide measurable neuroprotection. ONs from contralateral eyes exhibited subtle, complex changes in response to conditions in the bead eyes., Conclusions: S1R agonist (+)-PTZ shows promise as a neuroprotective treatment for glaucoma. Future studies to understand the complex molecular mechanisms by which (+)-PTZ provides this neuroprotection are needed., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Infections cause significant treatment-related morbidity during pediatric acute lymphoblastic leukemia/lymphoma (ALL/LLy) therapy. Fevers during periods without severe neutropenia are common, but etiologies are not well-described. This study sought to describe the bloodstream infection (BSI) and non-BSI risk in children undergoing therapy for ALL/LLy., Methods: Demographic and clinical data were abstracted for febrile episodes without severe neutropenia at two children's hospitals. Treatment courses were stratified by intensity. Multivariate logistic regression evaluated characteristics associated with infection., Results: There were 1591 febrile episodes experienced by 524 patients. Of these, 536 (34%) episodes had ≥1 infection; BSI occurred in 30 (1.9%) episodes. No BSIs occurred in episodes with a recent procedural sedation or cytarabine exposure. Presence of hypotension, chills/rigors, higher temperature, and infant phenotype were independently associated with BSI (p < .05). Of the 572 non-BSIs, the most common was upper respiratory infection (URI) (n = 381, 67%). Compared to episodes without infection, URI symptoms, higher temperature, absolute neutrophil count 500-999/μl, and evaluation during a low-intensity treatment course were more likely to be associated with a non-BSI (p < .05) and inpatient status was less likely to be associated with a non-BSI (p < .05)., Conclusions: The BSI rate in pediatric patients with ALL/LLy and fever without severe neutropenia is low, but one-third of the time, patients have a non-BSI. Future research should test if the need for empiric antibiotics can be tailored based on the associations identified in this study., (© 2022 American Cancer Society.)

Objective: Current guidelines recommend intervention in subjects with severe symptomatic aortic stenosis (AS), even though any degree of AS is associated with a higher risk of mortality. We investigated the association between the degree of AS, delineated by transvalvular flow velocity, and patient morbidity and mortality., Methods: Medically managed patients aged 40-95 years with maximum flow velocity (V max ) by echocardiography between 2013 and 2018 were stratified into five groups (A-E) based on the 75th, 90th, 97.5th, and the 99th percentiles of V max distribution. Patient characteristics, cardiac structural changes, and end-organ disease were compared using Kruskal-Wallis and Cochran-Armitage tests. Mortality over a median of 2.8 (1.52-4.8) years was compared using Kaplan-Meier curves and risk estimates were derived from the Cox model., Results: The V max was reported in 37,131 patients. There was a steady increase (from Group A towards E) in age, Caucasian race, structural cardiac changes, end-organ morbidities, and all-cause mortality. In reference to Group A, there as an increased risk of mortality in Groups B (hazard ratio [HR] = 1.3; confidence interval [CI]: 1.2-1.35; p < .0001), C (HR = 1.5; CI: 1.4-1.6; p < .0001), and D (HR = 1.8; CI: 1.6-2; p < .0001), with an exponential increase in Group E (HR = 2.5; CI: 2.2-2.8; p < .0001)., Conclusions: A direct, strong correlation exists between the degree of AS and cardiac structural changes and mortality. Patients with V max  ≥ 97.5th percentile (≥3.2 m/s) might benefit from early intervention., (© 2022 Wiley Periodicals LLC.)

There is limited literature on the characteristics of pediatric ophthalmology leadership. The authors examined the demographics, academic backgrounds, and scholarly output of pediatric ophthalmology fellowship program directors. Despite a positive trend in gender equity in this position, efforts remain to resolve the "leaky pipeline" of women into ophthalmology leadership. [ J Pediatr Ophthalmol Strabismus . 2022;59(6):e69-e72.] .

Background: Heterozygous loss of X-linked genes like CASK and MeCP2 (Rett syndrome) causes developmental delay in girls, while in boys, loss of the only allele of these genes leads to epileptic encephalopathy. The mechanism for these disorders remains unknown. CASK -linked cerebellar hypoplasia is presumed to result from defects in Tbr1-reelin-mediated neuronal migration., Method: Here we report clinical and histopathological analyses of a deceased 2-month-old boy with a CASK -null mutation. We next generated a mouse line where CASK is completely deleted (hemizygous and homozygous) from postmigratory neurons in the cerebellum., Result: The CASK -null human brain was smaller in size but exhibited normal lamination without defective neuronal differentiation, migration or axonal guidance. The hypoplastic cerebellum instead displayed astrogliosis and microgliosis, which are markers for neuronal loss. We therefore hypothesise that CASK loss-induced cerebellar hypoplasia is the result of early neurodegeneration. Data from the murine model confirmed that in CASK loss, a small cerebellum results from postdevelopmental degeneration of cerebellar granule neurons. Furthermore, at least in the cerebellum, functional loss from CASK deletion is secondary to degeneration of granule cells and not due to an acute molecular functional loss of CASK . Intriguingly, female mice with heterozygous deletion of CASK in the cerebellum do not display neurodegeneration., Conclusion: We suggest that X-linked neurodevelopmental disorders like CASK mutation and Rett syndrome are pathologically neurodegenerative; random X-chromosome inactivation in heterozygous mutant girls, however, results in 50% of cells expressing the functional gene, resulting in a non-progressive pathology, whereas complete loss of the only allele in boys leads to unconstrained degeneration and encephalopathy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Worldwide dissemination of extended-spectrum -lactamase (ESBL)-producing Escherichia coli constitutes an emerging global health issue, with animal food products contributing as potential reservoirs. ESBL E. coli infection is associated with the high mortality and mobility rate in developing countries due to less susceptibility to antibiotics. The present study aimed to elucidate the molecular characteristics and sequence-based analysis of ESBL E. coli in the Gujarat state of India. This study included 108 E. coli strains were isolated from different poultry farms (broiler and layer) in the Banaskantha District. PCR was employed to identify genotypic ESBL-producing antimicrobial resistance genes. Overall, a high occurrence of ESBL genes was found in poultry farms due to the high usage of antimicrobials. The PCR analysis revealed that 79.62% of isolates were detected positive with one or more ESBL genes. Among them, bla TEM (63.88%) was found to be the predominant genotype, followed by bla SHV (30.55%) and bla OXA (28.70%). In the bla CTX-M group, a higher occurrence was observed in bla CTX-M-9 (23.14%), followed by bla CTX-M-2 (24.07%) and bla CTX-M-1 (22.22%). We used the whole-genome sequencing (WGS) method to evaluate the antimicrobial resistance genes, virulence factors, single nucleotide polymorphisms (SNPs), plasmid replicons, and plasmid-mediated AMR genes of one ESBL E. coli isolated. We examined the genetic relatedness of a human pathogenic E. coli strain by comparing its sequence with the broad geographical reference E. coli sequences. Escherichia coli ST 681 was determined using multi-locus sequence typing. We compared our findings to the reference sequence of Escherichia coli str. K- 12 substr. MG1655. We found 24,937 SNPs with 21,792 in the genic region, 3,145 in the intergenic region, and six InDels across the genome. The WGS analysis revealed 46 antimicrobial resistance genes and seven plasmid-mediated AMR genes viz. , tetA , qnrS1, dfrA14 , sul2 , aph(3")-lb , aph(6)-ld , and Aph(3')-la . The ST 681 was found to have Cib , traT , and terC virulence factors and two plasmid replicons, IncFII(pHN7A8) and IncI1-I(Alpha). This study revealed a higher occurrence of ESBL E. coli detected in poultry., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Patel, Pandey, Patel, Patel, Chauhan, Shrimali, Patel, Mohapatra and Chandel.)

Introduction: Amidst the COVID-19 pandemic, telemedicine has emerged as a safe and cost-effective alternative to traditional ophthalmology clinic visits. This study evaluated patient attitudes towards telemedicine at a full-service, retina-only practice to identify areas for growth in implementation., Methods: A survey was distributed to established patients at University Retina and Macula Associates following the completion of a telemedicine encounter in July 2021. On a 5-point Likert scale, patients compared telemedicine to in-person visits for six domains: ability to ease COVID-related anxiety, efficiency, patient education, quality of care, fulfillment of personal needs, and convenience. Pearson's χ 2 and Fisher's exact test were used to assess correlations between demographic factors and patient attitudes or preference towards telemedicine., Results: Among 103 respondents, two-thirds (68.7%) preferred in-person compared to telemedicine encounters. Overall, patients had a neutral attitude towards telemedicine [mean Likert rating (SD) = 3.11/5 ± 0.82]. Questions assessing "patient education" and "telemedicine efficiency" received the greatest proportion of positive and negative responses, respectively. Positive attitudes were more frequent among patients with prior telemedicine experience (87.5%) compared to never-users (71.8%; p = 0.046). Patients ≥ 75 years old tended to negatively assess telemedicine regarding reduction of COVID-19-related anxiety, efficiency, patient education, and physician facetime (p < 0.05 for all). A positive but non-significant trend was observed between higher education level and positive attitude towards telemedicine (p = 0.18). Telehealth never-users more often negatively rated receiving adequate facetime with the physician virtually (54.7%) compared to prior users (25.6%; p = 0.004). Younger age, prior history of telemedicine use, and higher education level were associated with increased preference for telemedicine (p < 0.05 for all)., Conclusion: Our findings revealed hesitance remains among patients towards adoption of telemedicine. Targeting age-, experience-, and education-related barriers will be invaluable for increasing acceptance of this healthcare delivery model., (© 2022. The Author(s).)

Multiple sclerosis (MS) is a central nervous system (CNS) autoimmune disease characterized by inflammation, demyelination, and neurodegeneration. The ideal MS therapy would both specifically inhibit the underlying autoimmune response and promote repair/regeneration of myelin as well as maintenance of axonal integrity. Currently approved MS therapies consist of non-specific immunosuppressive molecules/antibodies which block activation or CNS homing of autoreactive T cells, but there are no approved therapies for stimulation of remyelination nor maintenance of axonal integrity. In an effort to repurpose an FDA-approved medication for myelin repair, we chose to examine the effectiveness of digoxin, a cardiac glycoside (Na + /K + ATPase inhibitor), originally identified as pro-myelinating in an in vitro screen. We found that digoxin regulated multiple genes in oligodendrocyte progenitor cells (OPCs) essential for oligodendrocyte (OL) differentiation in vitro, promoted OL differentiation both in vitro and in vivo in female naïve C57BL/6J (B6) mice, and stimulated recovery of myelinated axons in B6 mice following demyelination in the corpus callosum induced by cuprizone and spinal cord demyelination induced by lysophosphatidylcholine (LPC), respectively. More relevant to treatment of MS, we show that digoxin treatment of mice with established MOG 35-55 -induced Th1/Th17-mediated chronic EAE combined with tolerance induced by the i.v. infusion of biodegradable poly(lactide-co-glycolide) nanoparticles coupled with MOG 35-55 (PLG-MOG 35-55 ) completely ameliorated clinical disease symptoms and stimulated recovery of OL lineage cell numbers. These findings provide critical pre-clinical evidence supporting future clinical trials of myelin-specific tolerance with myelin repair/regeneration drugs, such as digoxin, in MS patients., (© 2022 The Authors. GLIA published by Wiley Periodicals LLC.)

This special article is the first in a planned annual series for the Journal of Cardiothoracic and Vascular Anesthesia that will highlight significant literature from the world of graduate medical education (GME) that was published over the past year. The major themes selected for this inaugural review are the educational value of simulation and training workshops, the expanding role of social media and other information technologies in GME and recruitment, the state of residency and fellowship training before the COVID-19 pandemic, and the inevitable effects COVID-19 has had on graduate medical education. The authors would like to thank the editorial board for allowing us to shine a light on a small subset of the writing and research produced in this field, so that educators may understand how best to educate and train the next generation of anesthesiologists., (Copyright © 2022 Elsevier Inc. All rights reserved.)

2021 and the COVID 19 pandemic have brought unprecedented blood shortages worldwide. These deficits have propelled national efforts to reduce blood usage, including limiting elective services and accelerating Patient Blood Management (PBM) initiatives. A host of research dedicated to blood usage and management within cardiac surgery has continued to emerge. The intent of this review is to highlight this past year's research pertaining to PBM and COVID-19-related coagulation changes., Competing Interests: Conflicts of Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Tranexamic acid (TXA) is a potent antifibrinolytic with documented efficacy in reducing blood loss and allogeneic red blood cell transfusion in several clinical settings. With a growing emphasis on patient blood management, TXA has become an integral aspect of perioperative blood conservation strategies. While clinical applications of TXA in the perioperative period are expanding, routine use in select clinical scenarios should be supported by evidence for efficacy. Furthermore, questions regarding optimal dosing without increased risk of adverse events such as thrombosis or seizures should be answered. Therefore, ongoing investigations into TXA utilization in cardiac surgery, obstetrics, acute trauma, orthopedic surgery, neurosurgery, pediatric surgery, and other perioperative settings continue. The aim of this review is to provide an update on the current applications and limitations of TXA use in the perioperative period., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 International Anesthesia Research Society.)

Renovascular hypertension in most cases requires endovascular treatment and/or surgery. This is technically much more difficult in small children and there is very limited published knowledge in this age group. We here present treatment and outcome of young children with renovascular hypertension at our institution. Children below 2 years of age, with renovascular hypertension between January 1998 and March 2020 were retrospectively reviewed. Demographics and treatment modalities were noted. Primary outcome was blood pressure within a week after the procedures and at last available visit. Sixty-six angiographies were performed in 34 patients. Median age at time of first angiography was 1.03 (interquartile range (IQR) 0.4-1.4) years and systolic blood pressure at presentation 130 (IQR 130-150) mm Hg. Thirty-eight percent (13/34) of children were incidentally diagnosed and 18% (6/34) presented with heart failure. Twenty-six (76%) children had main renal artery stenosis and 17 (50%) mid-aortic syndrome. Seventeen (50%) children showed intrarenal, six (18%) mesenteric, and three (9%) cerebrovascular involvement. Twenty patients underwent 45 percutaneous transluminal angioplasty procedures and seven children surgeries. In 44% of the 16 patients who underwent only percutaneous transluminal angioplasty blood pressure was normalized, 38% had improvement on same or decreased treatment and 19% showed no improvement. Complications were seen in 7.5% (5/66) of angiographies. In four of the seven (57%) children who underwent surgery blood pressure was normalized, two had improved (29%) and one unchanged (14%) blood pressure., Conclusion: In small children with renovascular hypertension below the age of 2 years, percutaneous transluminal angioplasty caused significant improvement in blood pressure with low complication profile. Surgery can be recommended where percutaneous transluminal angioplasty and medical treatments failed., What Is Known: • Renovascular hypertension is diagnosed in all age groups from a few weeks of life until adulthood. • Both angioplasty and surgery are significantly more difficult to perform in small children and the published information on short and long-term outcome in these children is very scarce., What Is New: • Children below the age of two years can safely and successfully undergo selective renal angiography and also safely be treated with angioplasty. • We here present a large group of babies and infants where angioplasty and in some cases surgery effectively and safely improved their blood pressure., (© 2022. The Author(s).)

Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in the elderly population. AMD is characterized in its late form by neovascularization (wet type) or geographic atrophy of the retinal pigment epithelium cell layer (dry type). Regarding the latter type, there is growing evidence supporting an association between the pathophysiology of dry AMD and key proteins in the complement cascade. The complement cascade works as a central part of the innate immune system by defending against foreign pathogens and modified self-tissues. Through three distinct pathways, a series of plasma and membrane-associated serum proteins are activated upon identification of a foreign entity. Several of these proteins have been implicated in the development and progression of dry AMD. Potential therapeutic targets include C1q, C3, C5, complement factors (B, D, H, I), membrane attack complex, and properdin. In this review, we provide an understanding of the role of the complement system in dry AMD and discuss the emerging therapies in early phase clinical trials. The tentative hope is that these drugs may offer the potential to intervene at earlier stages in dry AMD pathogenesis, thereby preventing progression to late disease.

Introduction: In 2021, over 3,000 articles on Drug-Induced Liver Injury (DILI) were published, nearly doubling the annual number compared to 2011. This review selected DILI articles from 2021 we felt held the greatest interest and clinical relevance., Areas Covered: A literature search was conducted using PubMed between 1 March 2021 and 28 February 2022. 86 articles were included. This review discusses new and established cases of hepatotoxins, including new FDA approvals and COVID-19 therapeutics. Developments in biomarkers and causality assessment methods are discussed. Updates from registries are also explored., Expert Opinion: DILI diagnosis and prognostication remain challenging. Roussel Uclaf Causality Assessment Method (RUCAM) is the best option for determining causality and has been increasingly accepted by clinicians. Revised Electronic Causality Assessment Method (RECAM) may be more user-friendly and accurate but requires further validation. Quantitative systems pharmacology methods, such as DILIsym, are increasingly used to predict hepatotoxicity. Oncotherapeutic agents represent many newly approved and described causes of DILI. Such hepatotoxicity is deemed acceptable relative to the benefit these drugs offer. Drugs developed for non-life-threatening disorders may not show a favorable benefit-to-risk ratio and will be more difficult to approve. As the COVID-19 landscape evolves, its effect on DILI deserves further investigation.

Background: A group of experts from different disciplines was convened to develop guidelines for the management of upper visual field impairments related to eyelid ptosis and dermatochalasis. The goal was to provide evidence-based recommendations to improve patient care., Methods: A multidisciplinary group of experts representing their specialty organizations was selected. A systematic literature review was performed including topics regarding documentation of the underlying cause for visual field impairment, selection of an appropriate surgical repair, assessment of the type of anesthesia, the use of adjunctive brow procedures, and follow-up assessments. The Grading of Recommendations, Assessment, Development, and Evaluation methodology process was used to evaluate the relevant studies. Clinical practice recommendations were developed using BRIDGE-Wiz (Building Recommendations In a Developers' Guideline Editor) software., Results: Each topic area was assessed. A clinical recommendation was made, and the relevant literature was discussed., Conclusions: The review of the literature revealed varied complication rates and diverse treatment modalities for the correction of upper visual field deficit. Strong recommendations could not be made in most topic areas because of a paucity of methodologically sound studies in the literature. More rigorously designed studies are needed to measure outcomes of interest, with fewer sources of potential error or bias., Clinical Question/level of Evidence: Therapeutic, V., (Copyright © 2022 by the American Society of Plastic Surgeons.)

(1) Background: The clinical burden of aortic stenosis (AS) remains high in Western countries. Yet, there are no screening algorithms for this condition. We developed a risk prediction model to guide targeted screening for patients with AS. (2) Methods: We performed a cross-sectional analysis of all echocardiographic studies performed between 2013 and 2018 at a tertiary academic care center. We included reports of unique patients aged from 40 to 95 years. A logistic regression model was fitted for the risk of moderate and severe AS, with readily available demographics and comorbidity variables. Model performance was assessed by the C-index, and its calibration was judged by a calibration plot. (3) Results: Among the 38,788 reports yielded by inclusion criteria, there were 4200 (10.8%) patients with ≥moderate AS. The multivariable model demonstrated multiple variables to be associated with AS, including age, male gender, Caucasian race, Body Mass Index ≥ 30, and cardiovascular comorbidities and medications. C-statistics of the model was 0.77 and was well calibrated according to the calibration plot. An integer point system was developed to calculate the predicted risk of ≥moderate AS, which ranged from 0.0002 to 0.7711. The lower 20% of risk was approximately 0.15 (corresponds to a score of 252), while the upper 20% of risk was about 0.60 (corresponds to a score of 332 points). (4) Conclusions: We developed a risk prediction model to predict patients' risk of having ≥moderate AS based on demographic and clinical variables from a large population cohort. This tool may guide targeted screening for patients with advanced AS in the general population.

Competing Interests: The authors have no conflicts of interest to declare.

Background: Limited research has examined differences between uncited papers and their most-cited counterparts. By comparing characteristics of each cohort, it is possible to better determine factors associated with increased citation count in the ophthalmology literature., Methods: We initially identified all research articles published in six popular general ophthalmology journals ( Ophthalmology, JAMA Ophthalmology, Investigative Ophthalmology and Visual Sciences, American Journal of Ophthalmology, British Journal of Ophthalmology , and Graefe's Archive for Clinical and Experimental Ophthalmology ) between 2001 and 2011. Forty-nine articles were identified as having accrued zero citations as of March 2021 and were compared with an equivalent number of articles with the highest number of citations published in the same journals and time period. Significance ( p < 0.05) for comparisons was determined using the Mann-Whitney U test and Fisher's exact test., Results: Compared to the least-cited articles, the most-cited articles were significantly more likely to be clinical, multi-institutional, and multi-national in scope, report a statistically significant result, have a conflict of interest, state a funding source, and have higher sample sizes. These publications had significantly more words in the abstract and manuscript and more references. Overall, the first authors of the most-cited articles were significantly more likely to be female and report greater prior research productivity, as assessed by the relative citation ratio (RCR)., Conclusion: Considering a small number of articles were uncited at least a decade after publication, it appears most research is useful for future investigations. However, there remain distinct differences between uncited articles and their most-cited equivalents in ophthalmology.

Race and ethnic backgrounds affect the disease characteristics and clinical outcomes in many cancers, including acute myeloid leukemia; however, the association of race/ethnicity on myelodysplastic syndrome (MDS) is still controversial. Therefore, we aimed to study the impact of race/ethnicity on the disease characteristics and survival outcomes in patients with MDS. Adult patients with MDS diagnosed in 2004-2016 were selected using the SEER database. Race/ethnicity was categorized as non-Hispanic White (NHW), non-Hispanic Black (NHB), and Hispanic. Hispanic and NHB patients had significantly lower incidence rate ratio (IRR) in age group ≥01 years ( p  < .001) compared to NHW; however, in the age group <50 years, NHB patients had significantly higher IRR with an increased incidence rate of 49%. NHB patients had better overall survival than Hispanic and NHW patients ( p  < .001), even after adjusting for confounding variables. MDS have significant differences in age at diagnosis, disease risk, and survival outcomes based on racial/ethnic backgrounds.

Venous thromboembolism (VTE), specifically deep vein thrombosis (DVT) and pulmonary embolism (PE), is a major complication in plastic surgery; however, there is a paucity of evidence about the incidence of VTE in the craniofacial subpopulation. We investigated the incidence and risk factors for VTE in the adult craniofacial trauma population., Methods: This retrospective review identified patients from the 2016 and 2017 Healthcare Cost and Utilization Project's National Inpatient Sample with a diagnosis for an initial encounter of a facial fracture. International Classification of Disease codes identified patients with DVT or PE. Groups were identified: adult craniofacial patients with and without a VTE diagnosis. The groups were analyzed to determine risk factors for developing a VTE during inpatient admissions., Results: A total of 203,240 patients were identified based on a diagnosis for an initial encounter of a facial fracture. Among those, 3350 (1.65%) were diagnosed with a DVT and 1455 (0.72%) with a PE. Risk factors for VTE were male sex ( P = 0.011), longer hospital stay ( P = 0.000), and higher Elixhauser comorbidity index ( P = 0.000). Additionally, PE was an independent predictor of mortality [odds ratio (OR), 2.129] but DVT was not (OR, 1.148). Cranial and frontal fractures were independently associated with an increase in DVT (OR, 2.481) and PE (OR, 1.489)., Conclusions: This study demonstrates that craniofacial trauma patients are at risk for VTE and should be risk-stratified for chemoprophylaxis therapy. Further studies in thromboembolism prophylaxis for facial fractures are warranted as the data are limited., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Purpose This study aims to examine the demographic features, academic backgrounds, and scholarly achievements of ophthalmic plastic and reconstructive surgery (OPRS) fellowship program directors (PDs) in the United States. Methods In this cross-sectional analysis, publicly accessible sources were accessed in March 2022 to collate the demographic and academic profiles of PDs of American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS)-accredited OPRS fellowships. Differences by gender and program rank were assessed using the Mann-Whitney Utest. Results Fifty-four PDs were identified, the majority of whom were males (88.89% (n = 48)). The average age was 58.48 years. Of the PDs, 96.3% (n = 53) obtained a medical degree, and all completed residency training in the United States. In addition, 9.26% (n = 5) had another degree, either a Doctor of Philosophy (n = 3) or master's degree (n = 2). A substantial proportion of individuals completed medical school (20.37% (n = 11)), residency (20.37% (n = 11)), or fellowship (31.48% (n = 17)) at an institution affiliated with the program where they were PDs. The most common additional fellowship obtained was neuro-ophthalmology (16.67% (n = 9)). The average h-index was 19.30 (range, 0-60), average five-year h-index was 4.85 (range, 0-36), and average m-quotient was 0.63 (range, 0-2.22). A significant difference in the median five-year h-index was observed between females and males (7 (range, 3-36) versus 4 (range, 0-10); p= 0.038). Conclusions This analysis indicated that OPRS PDs in the United States were principally males with extensive scholarly productivity. As women remain underrepresented in OPRS, increased gender parity at this leadership position should be encouraged in order to expand the recruitment of women into the field., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Patel et al.)

Purpose: To describe the magnitude, party affiliation, temporal trend, and geographic distribution of political contributions made by ophthalmologists in the United States., Methods: This cross-sectional study used public finance data from the Federal Election Commission website to identify political donations from ophthalmologists between 2003-2019. Contributions were filtered for occupation lines matching either "ophthalmologist," or "eye surgeon," and each contribution was cross-referenced to catalogue donations as "Republican," "Democratic," or "Independent.", Results: From 2003-2019, a total of 31,855 political donations were made by self-identified ophthalmologists, totaling $11,603,672. Of all dollars, 10.7%, 19.5%, and 69.8% went to Democratic, Republican, and Independent committees, respectively. Political contributions directed towards the American Academy of Ophthalmology Political Action Committee (OPHTHPAC) constituted the majority (59.8%) of overall contributions. From 2003 to 2019, the total number of unique contributions increased significantly from 1135 to 3208 (? = 0.63; P < .01). In dollars, this translated to an increase from $482,300 donated in 2003 to $640,695 donated in 2019, although this trend was non-significant (? = 0.18; P = .48). Conversely, the average amount of each contribution significantly declined from $425 to $203 (? = -0.35; P < .001). As expected, larger states such as California, Texas, Florida, Illinois, Michigan, and New York had the highest contribution dollars, in that order., Conclusions: Political contributions from ophthalmologists have significantly risen since 2003, however there remain opportunities for growth in engagement with OPHTHPAC. Future analysis of how this involvement translates to representative health policy is warranted.

Purpose: To determine the management and outcomes of patients with gastro-oesophageal reflux (GOR) that requires further intervention following failure of Nissen fundoplication (NF)., Methods: After institutional audit department approval, a retrospective review of paediatric patients who had further intervention following failure of primary NF between January 2006 and December 2015 for GOR at our centre was performed. Data are presented as median (range)., Results: Of 820 patients who underwent NF, 190 (23%) received further procedures for GOR management at a median of 21 months of age (6-186); 90/190 (47%) had gastro-jejunal feeding (GJ). Of these, 67 (74%) remained on GJ feeds up to a median of 48 months and 23/90 (26%) had a second NF after GJ feeding. 97/190 (51%) had a redo fundoplication without having had a GJ; thus, 120/190 (63%) of patients having a further procedure went on to have a second NF after a median period of 15 months (1-70 months). Three patients (2%) had early emergency wrap revision 4 days after first fundoplication (we classed this as an 'early complication'). Of the seven patients who failed a 3rd NF, 4 continued GJ feeding, 2 of had oesophagogastric dissociation; 2 had 4th NF of which 1 was successful and 1 patient had gastric pacemaker and is successfully feeding orally. Patients who were finally successfully managed with GJ underwent 2 (2-5) tube changes/year. We found patients who had a previous GJ were more likely to have failure of the redo fundoplication than those who had not to have the GJ (16/24 vs. 30/90, p = 0.005)., Conclusion: The chance of success decreases with every further attempt at fundoplication. The only factor significantly associated with failure of redo fundoplication was whether the patient previously had a GJ tube. In patients with failed fundoplications, when symptom free on jejunal feedings, further anti-reflux surgical intervention should be avoided. A randomized prospective study is needed for patient selection., (© 2022. Crown.)

Purpose: To analyze trends in National Institutes of Health (NIH) funding in ophthalmology and characterize its distribution to departments and principal investigators (PIs) affiliated with U.S. medical schools., Design: Longitudinal descriptive analysis., Methods: We queried publically accessible data from the Blue Ridge Institute for Medical Research and NIH RePORTER to determine annual funding trends in ophthalmology from 2009 to 2020. To characterize the distribution of funding, we further ranked the top departments and principal investigators (PIs). Department websites (among other online resources) were utilized to extract characteristics of the latter cohort., Results: After adjusting for inflation, we observed a modest 9% increase in median NIH funding to academic ophthalmology departments between 2009 and 2020. In the same time period, among individual PIs, this translated to a 9% decline in median funding. Our results among both departments and PIs indicated a persistent inequality in NIH funding. In 2020, 10 ophthalmology departments received 44% of total funding, which is consistent with findings from prior years. Our ranking of PIs by average annual NIH funding indicated a disproportionate representation of males (76%) and PhDs (58%) in the top 50., Conclusions: Overall, the results of this investigation suggest NIH funding remains limited for individual investigators, reflecting the increasingly competitive nature of the grant application process. Systemic alterations will be required to reverse these trends. If not accomplished, nascent and established researchers alike will continue to endure challenges in obtaining and maintaining funding.

Severe lung inflammation is common in life-threatening coronavirus disease 2019 (COVID-19). This study tested the hypothesis that polymorphonuclear (PMN, neutrophil) phenotype early in the course of disease progression would predict peak lung disease severity in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is increasingly evident that PMN activation contributes to tissue injury resulting from extracellular reactive oxygen species generation, granule exocytosis with release of proteases, neutrophil extracellular trap (NET) formation, and release of cytokines. The current study focuses on PMN activation in response to SARS-CoV-2 infection, specifically, the association between NETs and lung disease. This is a prospective cohort study at an academic medical center with patients enrolled within 4 days of admission at 3 tertiary hospitals: Clements University Hospital, Parkland Memorial Hospital, and Children's Health in Dallas, TX. Patients were categorized as having minimal or moderate to severe lung disease based on peak respiratory support. Healthy donor controls matched for age, sex, race, and ethnicity were also enrolled. Neutrophils from COVID-19 patients displayed greater IL-8 expression, elastase release, and NET formation as compared with neutrophils from healthy donors. Importantly, neutrophils from COVID-19 patients had enhanced NET formation in the absence of any additional stimulus, not seen in PMN from healthy donors. Moreover, PMA-elicited NET formation by circulating PMN correlated with severity of lung disease. We speculate that neutrophil immuno-phenotyping can be used to predict lung disease severity in COVID-19 patients., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Late cancellations and no-shows for surgery place a burden on patients, healthcare providers, and the health system. We aim to identify risk factors contributing to this phenomenon., Methods: Patients who did not arrive for, or canceled within 24 hours of, their surgical appointment between January 2019 and 2020 were identified. Controls were matched by date, procedure, and gender. Demographic information was obtained by phone interview and chart review. Chi-square and Student t-test analyses were used to predict risk factors for cancellation., Results: Thirty-one patients were identified, of whom 21 completed phone interviews. Age, gender, race, language, marital status, and smoking status were not significantly different. Study patients reported more transportation challenges (33.3% vs. 4.8%, p = .01) yet lived closer to the hospital (4.53 miles vs. 14.05 miles, p = .01). Study patients lived in lower income zip codes ($48,145 vs. $63,406, p = .02) and more commonly had Medicaid as their primary insurance (70.9% vs. 38.7%, p = .04). Most commonly, no reason was given for cancellation (22.6%) followed by personal reasons (16.1%) and surgery reconsideration (16.1%)., Conclusions: Transportation trouble and lower income are significant risk factors for surgery late cancellation. Prior no-show must also be considered. A targeted pilot program may help prevent late cancellations., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 National Association for Healthcare Quality.)

PurposeTo analyze research productivity, as assessed by the National Institutes of Health-supported relative citation ratio (RCR), for a cohort of Southern academic ophthalmologists.DesignA descriptive and cross-sectional design was used. Data on gender, academic rank (assigned as an assistant professor, associate professor, professor, or degrees, and career duration were collected using online resources. Research yield was quantified using mean and weighted RCR data queried from the iCite database. Significant between-group differences were calculated using the Mann-Whitney U -test and the Kruskal-Wallis test.SettingsPracticing academic ophthalmologists at Accreditation Council for Graduate Medical Education-accredited ophthalmology programs in the Southern United States (n = 1018).ResultsFor all Southern academic ophthalmologists, median mean RCR was 0.90 (IQR 0.18-1.71) and median weighted RCR was 5.12 (IQR 0.34-33.18). Advanced academic rank and PhD acquisition were significantly associated with increased mean and weighted RCR. After exclusion of faculty within the "other" category, median mean RCR was 1.12 (IQR 0.54-1.80) and median weighted RCR was 11.65 (IQR 2.03-45.58). Furthermore, effects of career duration and gender emerged. Ophthalmologists with longer careers had significantly higher mean and weighted RCR than their younger counterparts. Males had significantly higher mean and weighted RCR than females.ConclusionsAcademic rank and attainment of a PhD degree were correlated with increased research productivity. When analyses focused exclusively on faculty not in the "other" subgroup, male gender, and lengthier career were associated with increased mean and weighted RCR, the former of which potentially highlights differences in professional advancement between genders.

Introduction: Medical centers have dramatically increased the use of magnetic resonance imaging (MRI). At 2 large academic tertiary care centers in New York City, nearly half of inpatient MRI orders took more than 12 h to complete, delaying patient discharge and increasing avoidable hospital days. We posited that transitioning inpatient MRIs to outpatient facilities, when safe and appropriate, could reduce inpatient MRI orders and avoidable hospital days., Methods: We manually reviewed 59 inpatient MRI orders delayed on the estimated date of discharge (EDD). These orders were often delayed due to no standard process to escalate orders for medical reasons or no system to coordinate outpatient orders. We developed a revised workflow involving an automation platform that flagged inpatient MRI orders requested within 24 h of the EDD and emailed the care team to request a second review of the order. The care team reconsidered whether the order was (1) required for discharge, (2) non-urgent and could be converted to an outpatient order, or (3) unnecessary and could be canceled., Results: Over 9 months, the automation platform flagged 618 inpatient MRI orders, of which 53.9% (333/618) were reviewed by the care team. Among the orders, 24.0% (80/333) of reviewed orders and 12.9% (80/618) of all orders were transitioned to either outpatient or canceled orders. These transitioned orders were associated with 267 fewer avoidable hospital days and a cost savings of $199,194., Conclusion: A standardized process and second review of inpatient MRI orders on the EDD can reduce inappropriate orders and more effectively use inpatient imaging resources., Precis: A standardized workflow and automation platform encouraged a second review of inpatient MRI orders to reduce inappropriate orders, avoidable hospital days, and hospital costs., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Cancer is one of the major leading causes of death worldwide. Accumulating evidence suggests a strong relationship between specific dietary habits and cancer development. In recent years, a food-based approach for cancer prevention and intervention has been gaining tremendous attention. Among diverse dietary and medicinal plants, lotus ( Nelumbo nucifera Gaertn., family Nymphaeaceae), also known as Indian lotus, sacred lotus or Chinese water lily, has the ability to effectively combat this disease. Various parts of N. nucifera have been utilized as a vegetable as well as an herbal medicine for more than 2000 years in the Asian continent. The rhizome and seeds of N. nucifera represent the main edible parts. Different parts of N. nucifera have been traditionally used to manage different disorders, such as fever, inflammation, insomnia, nervous disorders, epilepsy, hypertension, cardiovascular diseases, obesity, and hyperlipidemia. It is believed that numerous bioactive components, including alkaloids, polyphenols, terpenoids, steroids, and glycosides, are responsible for its various biological and pharmacological activities, such as antioxidant, anti-inflammatory, immune-modulatory, antiviral, hepatoprotective, cardioprotective, and hypoglycemic activities. Nevertheless, there is no comprehensive review with an exclusive focus on the anticancer attributes of diverse phytochemicals from different parts of N. nucifera . In this review, we have analyzed the effects of N. nucifera extracts, fractions and pure compounds on various organ-specific cancer cells and tumor models to understand the cancer-preventive and therapeutic potential and underlying cellular and molecular mechanisms of action of this interesting medicinal and dietary plant. In addition, the bioavailability, pharmacokinetics, and possible toxicity of N. nucifera -derived phytochemicals, as well as current limitations, challenges and future research directions, are also presented.

Purpose: Soccer participation within the United States continues to increase, necessitating consideration of the various injuries that may occur. The present study analyzes trends in the incidence of ocular injuries secondary to soccer trauma, the associated mechanism, and related visual sequelae, and quantifies age- and sex-specific differences in the distributions of these variables., Methods: The Consumer Product Safety Commission's National Electronic Injury Surveillance System (NEISS) was queried for soccer-related ocular injuries from 2010 through 2019. Data exclusively focused on the globe were selected, and information regarding age, sex, specific diagnosis, mechanism of injury, and visual sequelae were acquired. Significance was calculated using the chi-squared test., Results: 628 NEISS entries were evaluated, extrapolating to a national average incidence of approximately 1580 soccer-related ocular injuries per year. There were a relatively static number of events during the ten-year time period of study. The most common diagnoses were contusions or abrasions (36.1%); among records with a reported mechanism of injury, the most common was contact with the soccer ball (80.9%). Visual sequelae were noted in a significant minority of patients (15.4%). Patients ≤18 and males comprised the majority of visits (68.2% and 70.2%, respectively). Significant sex- and age-specific differences were observed in the distributions of diagnoses., Conclusions: There are serious visual consequences associated with soccer-related ocular injury. Despite the existence of eye protection, there remain no regulations requiring its consistent use. Therefore, among all parties involved (e.g., players, families, and physicians), there remains a need to increase education regarding the potential ocular dangers associated with the sport.

Introduction: The internet is an increasingly important resource for patients seeking health-related information. Because of this trend, the American Medical Association (AMA) and National Institutes of Health (NIH) recommend that online patient education materials (PEMs) be written between a third and seventh grade level. The present study evaluates the readability levels of ophthalmological PEMs provided by five major academic hospitals, quantifies the availability of accompanying videos and graphics, and examines the extent to which readability may be increased., Methods: In March 2021, 397 PEMs from five major academic hospitals were extracted for subsequent analysis by seven validated readability assessments. The presence of an accompanying video or graphic was noted. Statistical significance was assessed using the Kruskal-Wallis test with Dunn's multiple comparisons test and the chi-square test., Results: Nearly all articles were written above the recommended reading level of 7 th grade. After averaging the scales for each article, the median grade level was 11.7 (interquartile range [IQR], 10.7-12.7). The PEMs with the highest median reading level were provided by the Johns Hopkins University Wilmer Institute (12.6, IQR, 11.3 - 13.6). Only 13.6% and 13.1% of articles had an accompanying video and graphic, respectively. Reduction of sentence length beneath 15 words resulted in an improvement of readability by 2.7 grade levels., Conclusions: The readability of online patient resources provided by major academic hospitals were above the literacy guidelines recommended by the NIH and AMA. Furthermore, most articles did not include a video or graphic, both of which could potentially improve patient understandability of educational materials. By altering these PEMs, as demonstrated here, institutions could increase the value these articles provide for patients and therefore the quality of the patient-physician relationship.