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Background: Objective measures of research influence are being increasingly utilized to evaluate and compare academic faculty. However, traditional bibliometrics, such as the Hirsch index and article citation count, are biased by time-dependent factors and are limited by a lack of field normalization. The relative citation ratio (RCR) is a new field- and time-normalized article-level metric developed by the National Institutes of Health (NIH)., Purpose/hypothesis: The purpose of this study was to evaluate the RCR among fellowship-trained academic sports medicine surgeons and to analyze physician factors associated with RCR values. We hypothesized that the mean RCR score for fellowship-trained academic sports medicine surgery faculty will fall above the NIH standard., Study Design: Cross-sectional study., Methods: A retrospective data analysis was performed using the iCite database for all fellowship-trained sports medicine surgery faculty associated with Accreditation Council for Graduate Medical Education-accredited orthopaedic surgery residency programs in December 2021. In eligible faculty, the mean RCR, weighted RCR, and total publication count were compared by sex, career duration, academic rank, and presence of additional degrees. A mean RCR value of 1.0 is the NIH-funded field-normalized standard. The data herein are presented as the median and interquartile range, in addition to the mean and standard deviation, to account for outliers of the mean and weighted RCR scores., Results: A total of 624 fellowship-trained sports medicine surgery faculty members from 160 orthopaedic surgery residency programs were included in the analysis. Overall, faculty produced impactful research, with a median RCR of 1.6 (interquartile range, 1.0-2.2) and a median weighted RCR of 19.3 (interquartile range, 5.1-69.3). Advanced academic rank and career longevity were associated with increased weighted RCR and total publication count. All subgroups analyzed had an RCR value >1.0., Conclusion: Study findings indicate that fellowship-trained academic sports medicine surgery faculty are highly productive and produce impactful research, as evidenced by the high median RCR value relative to the benchmark NIH RCR value of 1.0., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: R.P. has received education payments from Arthrex. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2023.)

Purpose: To determine short- to midterm patient-reported outcomes of arthroscopic soft-tissue interposition arthroplasty using acellular dermal allograft with a minimum follow-up of 1 year and to assess outcomes in patients with and without flattening of the humeral head., Methods: Patients with a diagnosis of primary glenohumeral arthritis who underwent arthroscopic soft-tissue interposition arthroplasty with an acellular dermal allograft from July 2010 to November 2019 were retrospectively enrolled. Inclusion criteria were a primary diagnosis of glenohumeral arthritis and Outerbridge 4 full-thickness cartilage loss of ≥50% of the glenoid articular surface. Patients underwent arthroscopic debridement, microfracture, and biological arthroscopic soft-tissue interposition arthroplasty with an acellular dermal matrix. Postoperative outcomes included American Shoulder and Elbow Surgeon (ASES) score, Single Assessment Numeric Evaluation (SANE) score, Penn Shoulder Score (PSS), numeric rating scale (NRS) pain score, analgesic use, and conversion to total shoulder arthroplasty (TSA). Results were stratified according to humeral head morphology on preoperative radiographs., Results: A total of 25 patients were included, with a mean age of 56.0 years (range 19.2 to 74.8) and a mean follow-up of 3.36 years (range 1.03 to 8.98). The mean postoperative ASES score was 64.1 (range 11.7 to 100.0), SANE score was 62% (range 5% to 100%), and PSS was 61.2 (range 10.6 to 97.9). Additionally, 56% of patients rated their shoulder function as improved or much improved, and 36% of patients converted to TSA at a mean of 2.35 years. Patients with and without humeral flattening had similar postoperative ASES scores ( P  = .44), SANE scores ( P  = .90), PSS ( P  = .73), and conversions to TSA ( P  = .83). Patients with humeral flattening were more likely to have shoulder pain at night (83.3% versus 28.6%, P  = .02)., Conclusion: Arthroscopic soft-tissue interposition arthroplasty with an acellular dermal allograft resulted in satisfactory short- to mid-term postoperative outcomes for younger patients with glenohumeral arthritis but demonstrated a TSA conversion rate of 36%. Patients with humeral head flattening also had satisfactory shoulder function but were more likely to experience shoulder pain at night., Level of Evidence: Level IV, therapeutic case series., (© 2021 by the Arthroscopy Association of North America. Published by Elsevier Inc.)

Background: There remains an important need for prophylactic anti-Ebola virus vaccine candidates that elicit long-lasting immune responses and can be delivered to vulnerable populations that are unable to receive live-attenuated or viral vector vaccines., Methods: We designed novel synthetic anti-Ebola virus glycoprotein (EBOV-GP) DNA vaccines as a strategy to expand protective breadth against diverse EBOV strains and evaluated the impact of vaccine dosing and route of administration on protection against lethal EBOV-Makona challenge in cynomolgus macaques. Long-term immunogenicity was monitored in nonhuman primates for >1 year, followed by a 12-month boost., Results: Multiple-injection regimens of the EBOV-GP DNA vaccine, delivered by intramuscular administration followed by electroporation, were 100% protective against lethal EBOV-Makona challenge. Impressively, 2 injections of a simple, more tolerable, and dose-sparing intradermal administration followed by electroporation generated strong immunogenicity and was 100% protective against lethal challenge. In parallel, we observed that EBOV-GP DNA vaccination induced long-term immune responses in macaques that were detectable for at least 1 year after final vaccination and generated a strong recall response after the final boost., Conclusions: These data support that this simple intradermal-administered, serology-independent approach is likely important for additional study towards the goal of induction of anti-EBOV immunity in multiple at-risk populations.

Mitochondrial dysfunction is thought to be a hallmark of traumatic brain injury (TBI) and plays a pivotal role in the resulting cellular injury. Cyclophilin D-mediated activation of the mitochondrial permeability transition pore has been suggested to contribute to this secondary injury cascade. Cyclosporine possesses neuroprotective properties that have been attributed to the desensitization of mitochondrial permeability transition pore activation. In vivo animal experiments have demonstrated neuroprotective effects of cyclosporine in more than 20 independent experimental studies in a multitude of different experimental models. However, the majority of these studies have been carried out in rodents. The aim of the present study was to evaluate the efficacy of a novel and cremophor/kolliphor EL-free lipid emulsion formulation of cyclosporine in a translational large animal model of TBI. A mild-to-moderate focal contusion injury was induced in piglets using a controlled cortical impact device. After initial step-wise analyses of pharmacokinetics and comparing with exposure of cyclosporine in clinical TBI trials, a 5-day dosing regimen with continuous intravenous cyclosporine infusion (20 mg/kg/day) was evaluated in a randomized and blinded placebo-controlled setting. Cyclosporine reduced the volume of parenchymal injury by 35%, as well as improved markers of neuronal injury, as measured with magnetic resonance spectroscopic imaging. Further, a consistent trend toward positive improvements in brain metabolism and mitochondrial function was observed in the pericontusional tissue. In this study, we have demonstrated efficacy using a novel cyclosporine formulation in clinically relevant and translatable outcome metrics in a large animal model of focal TBI.

Objectives: Controversy remains regarding the use of deep hypothermic circulatory arrest (DHCA) in neonatal cardiac surgery. Alterations in cerebral mitochondrial bioenergetics are thought to contribute to ischaemia-reperfusion injury in DHCA. The purpose of this study was to compare cerebral mitochondrial bioenergetics for DHCA with deep hypothermic continuous perfusion using a neonatal swine model., Methods: Twenty-four piglets (mean weight 3.8 kg) were placed on cardiopulmonary bypass (CPB): 10 underwent 40-min DHCA, following cooling to 18°C, 10 underwent 40 min DHCA and 10 remained at deep hypothermia for 40 min; animals were subsequently rewarmed to normothermia. 4 remained on normothermic CPB throughout. Fresh brain tissue was harvested while on CPB and assessed for mitochondrial respiration and reactive oxygen species generation. Cerebral microdialysis samples were collected throughout the analysis., Results: DHCA animals had significantly decreased mitochondrial complex I respiration, maximal oxidative phosphorylation, respiratory control ratio and significantly increased mitochondrial reactive oxygen species (P < 0.05 for all). DHCA animals also had significantly increased cerebral microdialysis indicators of cerebral ischaemia (lactate/pyruvate ratio) and neuronal death (glycerol) during and after rewarming., Conclusions: DHCA is associated with disruption of mitochondrial bioenergetics compared with deep hypothermic continuous perfusion. Preserving mitochondrial health may mitigate brain injury in cardiac surgical patients. Further studies are needed to better understand the mechanisms of neurological injury in neonatal cardiac surgery and correlate mitochondrial dysfunction with neurological outcomes.

Currently, no reliable biomarkers are available to predict transformation from smoldering myeloma (SMM) to multiple myeloma (MM). Using an ultrasensitive enzyme-linked immunosorbent assay (ELISA) we assessed the levels of a broad range of cytokines and chemokines in the peripheral blood (PB) and bone marrow (BM) supernatant collected from 14 SMM and 38 MM patients and compared to healthy donors. We found significantly increased levels of key cytokines, in particular CXCL8 (IL-8), associated with progressive disease state (controls→SMM→MM). Cytokine profiles were found similar in PB and BM. Five of fourteen SMM patients (36%) progressed to MM. Our findings, although based on a limited number of patients, suggest that serum-based cytokines may have a future role as biomarkers for disease progression and could potentially be assessed as novel targets for treatment., (Published by Elsevier Ltd.)

Importance: Adherence with topical glaucoma medications is low in some patients. To identify these patients, we need more information on risk factors for nonadherence., Objective: To assess adherence with once-daily glaucoma medication., Design, Setting, and Participants: Prospective cohort study involving patients who were recruited from a university-based glaucoma clinic and treated with once-daily prostaglandin eyedrops. Baseline characteristics were recorded, and each patient was provided a medication bottle to hold his or her eyedrop bottle throughout the study. An electronic cap recorded each time the larger bottle holding the eyedrops was opened. Participants were administered standardized tests of depression and mental status and answered questions about their health and their attitudes toward medication adherence. They used the electronic monitors for 3 months, during which their adherence with medications was assessed., Main Outcomes and Measures: Adherence with daily glaucoma medication and factors associated with poor adherence., Results: Of the 491 participants enrolled, 407 (82.9%) successfully completed the 3-month adherence assessment. Of this group, 337 (82.8%) took their medication correctly on at least 75% of days and were deemed adherent. Compared with this adherent group, the 70 participants (17.2%) who were nonadherent were slightly younger, were more likely to be of African descent, took medications for a shorter time, had a lower level of educational attainment, and had worse scores on mental status and depression scales (P < .05 for all). Nonadherent participants were less likely to be able to name their glaucoma medications, reported a lower estimate of adherence, and were more likely to admit some missed doses over the past 2 weeks or in general (P < .05 for all). Those who were nonadherent were also less likely to agree that remembering their eyedrops is easy, more likely to strongly agree with the statement that eyedrops can cause problems, and less likely to agree that they followed physicians' orders., Conclusions and Relevance: Electronic monitoring of patient adherence documented that a sizable number of patients with glaucoma do not take their medications as prescribed. Factors were identified that may prove useful in targeting those nonadherent patients for interventions.

Importance: Topical glaucoma medications lower intraocular pressure and alter the course of the disease. Because adherence with glaucoma medications is a known problem, interventions are needed to help those patients who do not take their medications as prescribed., Objective: To assess the ability of an automated telecommunication-based intervention to improve adherence with glaucoma medications., Design, Setting, and Participants: We performed a prospective cohort study of medication adherence, followed by a randomized intervention for those found to be nonadherent, of individuals recruited from a university-based glaucoma subspecialty clinic. A total of 491 participants were enrolled in the initial assessment of adherence. Of those, 70 were nonadherent with their medications after 3 months of electronic monitoring and randomized to intervention and control groups., Interventions: A personal health record was used to store the list of patient medications and reminder preferences. On the basis of those data, participants randomized to the intervention received daily messages, either text or voice, reminding them to take their medication. Participants randomized to the control group received usual care., Main Outcomes and Measures: Difference in adherence before and after initiation of the intervention., Results: Using an intent-to-treat analysis, we found that the median adherence rate in the 38 participants randomized to the intervention increased from 53% to 64% (P < .05). There was no statistical change in 32 participants in the control group. To assess the real efficacy of the intervention, the same comparison was performed for the participants who successfully completed the study after randomization. Analyzed this way, the adherence rate in the 20 participants in the intervention group increased from 54% to 73% (P < .05), whereas there was again no statistical change in the 19 participants in the control group. Eighty-four percent of the participants who received reminders agreed they were helpful and would continue using them outside the study., Conclusions and Relevance: Automated telecommunication-based reminders linked to data in a personal health record improved adherence with once-daily glaucoma medications. This is an effective method to improve adherence that could realistically be implemented in ophthalmology practices with a minimum amount of effort on the part of the practice or the patient.

Objective: To develop and validate a predictive model to estimate the probability of being nonadherent to topical glaucoma medications., Design: Prospective cohort study., Participants: Patients being treated with once-daily prostaglandin eye drops., Methods: A predictive model for nonadherence was developed from the Travatan Dosing Aid (TDA) study (n = 196) using stepwise logistic regression. The performance of the TDA-derived model was assessed using a separate cohort of subjects from the Automated Dosing Reminder Study (ADRS; n = 407). The assessment was based on regression coefficients, discrimination, and calibration. We also developed a scoring system from the TDA-derived model to simplify the estimation of risk for clinical use., Main Outcome Measures: Usage of drops was monitored electronically for 3 months in both studies. Adherence was calculated as the percentage of days on which a dose was taken within 4 hours of the average dosing time for that patient. Nonadherence was defined as taking ≤ 75% prescribed doses within a window starting 2 weeks after the baseline visit until 2 weeks before the follow-up visit., Results: Six factors, including younger age, black race, worse general health status, shorter duration of glaucoma medication therapy, lower self-reported adherence, and admitting to not following doctors' orders, were associated with being nonadherent and were included in the predictive model. The coefficients for the TDA-derived and the ADRS-derived predictive models were similar. The risk scoring system developed from the TDA study had good discrimination (area under the receiver operating characteristic curve of 0.80) and calibration (Hosmer-Lemeshow goodness-of-fit test, P = 0.102) when applied to the ADRS population., Conclusions: The TDA-derived predictive model for nonadherence performed well in an independent population. A risk scoring system was developed using demographic data and patient responses to 4 questions to provide an estimate of the probability of being nonadherent., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)