bluuebunny/crossref_metadata_2025_split huggingface dataset:
P-775. Unlocking Synergistic Potency: Dual Action of β-Lactam and β-Lactamase Inhibitor in Combating Mycobacterium abscessus through β-Lactamase Inhibition and Multi-Target Receptor Inactivation
Authors: Shin Eunjeong , Dousa Khalid M , Bethel Christopher , Nantongo Mary , Holland Steven M , Rubin Eric , Bulitta Jürgen B , Kreiswirth Barry N , Bonomo Robert A 
Published: January 2025

Abstract

Background
Mycobacterium abscessus (Mab) poses significant clinical challenges, leading to chronic pulmonary disease in immunocompromised patients. Current treatment involve amikacin (AMK), which is toxic, highlighting the imperative for safer options. This study continues our evaluation of the synergistic effects of a β-lactam and β-lactamase inhibitor (BL/BLI) against Mab and to elucidate the underlying mechanism.
The inhibition constant (Ki,app)

Methods
The binding affinities and chemical interactions between target receptors (LDT1-5, DDC, PBP B, and PBP-lipo) and BL/BLI were determined via kinetics, mass spectrometry, DSF, flow cytometry and microscopy. The synergistic effects of BL/BLI were evaluated in time-kill studies, conducted over 10 days, using ATCC 19977 producing BlaMab.
Time-kill curves of monotherapy or double β-lactams (A, D, and G) and their combinations with avibactam (B, E, and H) or durlobactam+sulbactam (C, F, and I).

Results
Imipenem (IPM) showed high binding affinities for both LDTs and PBPs, with an extremely low inhibition constant (Ki,app; Tab. 1). Cephalosporins exhibited moderate binding affinity for both LDTs and PBPs, whereas amoxicillin (AMX) selectively targeted PBPs. The inactivation of BlaMab and LDTs/PBPs by durlobactam (DUR) exhibited greater efficacy compared to avibactam (AVI), aligning with their respective bactericidal effects. DUR showed a 75-fold lower Ki,app for BlaMab in comparison to AVI. The Ki,app of DUR for PBP B, PBP-lipo, and LDT2 fell below the clinical concentration, whereas those of AVI did not. Single β-lactam treatment resulted in minimal killing (∼1 log10 reduction), but adding AVI significantly enhanced killing by inhibition of β-lactamase (∼4 log10 reduction for IPM+AVI and ∼2 log10 reduction for others; Fig. 1). DUR alone showed 2 log10 reduction, and when combined with IPM or dual BL, it achieved near-eradication, surpassing the SOC (AMK + Clarithromycin + IPM or cefoxitin). Inhibition of PBP-lipo by sulopenem, IPM, DUR, and AMX changed the cell morphology to filaments. In accordance with the binding affinity to LDTs and PBPs, alterations in melting temperature were detected.

Conclusion
IPM + DUR + SUL showed the most killing of Mab with limited regrowth. This outcome can be attributed to β-lactamase inhibition and the inactivation of multiple targets, not only LDTs but also PBPs. This combination strategy holds promise for enhanced efficacy of Mab treatment, necessitating further study in clinical trials.

Disclosures
All Authors: No reported disclosures
P-778. Antimicrobial Effect of Nitric Oxide on Cystic Fibrosis Pathogens
Authors: Gibson Joy E , Youssef Christopher I , Neely Michael N 
Published: January 2025

Abstract

Background
Despite highly effective modulator therapy, bacterial pathogens persist in the airways of children and adults with CF. Staphylococcus aureus (Sa) and Pseudomonas aeruginosa (Pa) are most commonly identified, but others like Mycobacterium abscessus complex (MABSC) and Burkholderia cepacia complex (Bcc) are particularly challenging due to the high frequency of intrinsic and acquired antibiotic resistance. Treatment options for MABSC are limited, requiring prolonged exposure to multiple antibiotics that may cause significant toxicity and frequent failure. Novel treatment approaches are a high priority for management of infections in people with CF. One potential adjunctive therapy is inhaled nitric oxide (NO), which is frequently used in ventilated patients and has been explored for treatment of several pulmonary infections, given its antimicrobial properties.

Methods
In this study, we compared NO response in Sa, Pa, MABSC, and Bcc. We used chemical donors of NO, DETA NONOate and PAPA NONOate, to provide continuous or intermittent exposure, respectively, and compared growth curves assessed by OD600 over 24 hours for Sa, Pa, and Bcc, and 7 days for MABSC. We also exposed MABSC to different concentrations and frequencies of DETA and PAPA NONOate to determine the pharmacodynamics of this effect. To better correlate with clinical use, we further compared growth inhibition with gaseous NO delivered at 160 ppm thrice daily.

Results
We found that treatment with NONOate resulted in near complete inhibition of growth in MABSC at all concentrations, dose-dependent inhibition of Pa and Bcc, with a more potent affect on Bcc growth, and minimal growth inhibition of Sa. We quantified the minimum inhibitory concentration (MIC) of DETA NONOate in MABSC to be 660 µM and found the effect of NO on MABSC to be time-dependent based on linear regression of delta CFU relative to time above MIC (R2 =0.848), peak to MIC (R2 =0.344), and area under the curve to MIC (R2 =0.745). Gaseous NO resulted in greater than 50% growth inhibition of MABSC, but no inhibition in Pa or Bcc.

Conclusion
These findings indicate that inhaled NO may be a promising adjunctive therapy for treatment of MABSC, but may be less effective against other CF pathogens.

Disclosures
All Authors: No reported disclosures
P-781. The Impact of Hepatitis B Virus Infection on the Management of Latent Tuberculosis Infection in Northern California, 2010-2022
Authors: Fink Julia R , Dong Zinnia , Murrill Matthew , Wong Robert J , Chitnis Amit S , Jaganath Devan , Tang Amy S 
Published: January 2025

Abstract

Background
Tuberculosis (TB) and hepatitis B virus (HBV) infection affect similar at-risk populations. However, there is limited data on how co-infection may influence clinicians’ decision to offer TB preventative treatment (TPT) over concern for hepatotoxicity. We compared TPT by HBV status, and determined factors associated with TPT initiation among HBV-infected persons at a community health center in Northern California serving a large non-U.S.-born Asian population.

Methods
We extracted electronic health record data for all persons aged ≥18 years old with latent TB infection (LTBI), defined by a positive tuberculin skin test or interferon-gamma release assay in the absence of a TB disease diagnosis from 2010-2022. HBV infection was defined by a single positive HBV DNA or HBV surface antigen assay. We conducted multivariate logistic regression to explore the impact of (a) HBV status and (b) clinical and demographic variables on TPT initiation. We also examined how these factors changed when Rifampin (RIF) usage for TPT increased at this community health center after 2014.

Results
A total of 11,711 persons had LTBI and 5,530 had HBV. Of all persons with LTBI, 833 (9.0%) of those tested for HBV had a co-infection including 41 (4.9%) on HBV antiviral treatment; while 34% of all HBV-infected persons screened for TB had LTBI. Adjusting for demographics and time period, TPT was significantly lower among those with co-infection than those without (43.5% versus 47.4%, adjusted Odds Ratio (aOR) 0.76, 95% Confidence Interval (CI) 0.66 – 0.88, p&lt; 0.01). Among those with co-infection, increasing age (50-64, ≥65 years), and elevated alanine transaminase (ALT) levels were associated with decreased likelihood of TPT (Table 1). Treatment of co-infected individuals was significantly higher after 2014 when RIF prescribing increased (aOR 2.76, 95% CI 1.81-4.2); however, age over 65 was still associated with decreased TPT prescription (aOR 0.36, 95% 0.19 – 0.67, p &lt; 0.01).

Conclusion
HBV-LTBI co-infection was associated with reduced odds of TPT. Increased use of Rifamycin based regimens and further guidance on TPT and monitoring of older individuals and persons with elevated ALT levels may be needed to improve TB prevention efforts among HBV-LTBI co-infected persons.

Disclosures
Robert J. Wong, MD, MS, Durect Corporation: Grant/Research Support|Exact Sciences: Grant/Research Support|Gilead Sciences: Grant/Research Support|Thera Technologies: Grant/Research Support
Gait Speed Modifies Efficacy of Home-Based Exercise for Falls in Older Adults with a Previous Fall: Secondary Analysis of a Randomized Controlled Trial
Authors: Rice Jordyn , Falck Ryan S , Davis Jennifer C , Hsu Chun Liang , Dian Larry , Madden Kenneth , Parmar Naaz , Cook Wendy L , Khan Karim M , Liu-Ambrose Teresa 
Published: January 2025

Abstract

Objective
Exercise is an evidence-based strategy for preventing falls. However, its efficacy may vary based on individual characteristics, like gait speed. The study examined whether baseline gait speed modified the effects of home-based exercise on subsequent falls among older adults.

Methods
This is a secondary analysis of a 12-month, randomized controlled trial in community-dwelling adults who were ≥ 70 years old and who had fallen within the previous 12 months. Participants were randomized to either 12 months of home-based exercise (n = 172) or standard of care (n = 172). This study examined intervention effects on fall rates at 6 and 12 months stratified by baseline gait speed (slow [&lt;0.80 m/s] or normal [≥0.80 m/s]) using negative binomial regressions. Baseline gait speed was investigated as a potential modifier of the intervention effects on mobility and cognitive function using linear mixed modeling.

Results
At baseline, 134 participants had slow (exercise = 70; standard of care = 64) and 210 had normal (exercise = 102; standard of care = 108) gait speeds. For participants with slow gait speed, exercise reduced fall rates by 44% at 6 months (incidence rate ratio = 0.56; 95% CI = 0.33 to 0.95) but not at 12 months (incidence rate ratio = 0.63; 95% CI = 0.38 to 1.03) compared with standard of care; for participants with normal gait speed, there was no significant effect of exercise on fall rates at 6 or 12 months. Gait speed modified intervention effects; in the exercise group, participants with slow gait showed significant improvements in the Timed “Up & Go” Test at 6 months (estimated mean difference = −4.05; 95% CI = −6.82 to −1.27) and the Digit Symbol Substitution Test at 12 months (estimated mean difference = 2.51; 95% CI = 0.81 to 4.21).

Conclusion
Older adults with slow gait speed had a reduction in subsequent falls in response to exercise at 6 months. Gait speed modified the effects of exercise on mobility and cognition.

Impact
Older adults with slow gait speed may be a target population for exercise-based fall prevention.
Aphra Behn, Anne Wharton, and the Remaking of Rochester’s Reputation
Authors: Wright Gillian 
Published: January 2025

Abstract
Restoration scholarship has often assumed both that Aphra Behn and the Earl of Rochester were personally acquainted and that Rochester was an important influence on Behn’s writing. This article reassesses the evidence for a literary relationship between Behn and Rochester, most of which postdates Rochester’s death in 1680. Focusing in particular on two poems by Behn—‘To Mrs W.’, addressed to Rochester’s niece, Anne Wharton, and her elegy ‘On the Death of the late Earl of Rochester’—it argues that what may look like a literary relationship between Behn and Rochester is often and more importantly a connection between Behn and Wharton. Positing a late (1685) date for ‘On the Death of the late Earl of Rochester’, it reframes its likely role within Behn’s career, and links it with wider efforts led by Wharton to refashion Rochester’s reputation after his death. It also explores the implications of the Behn-Wharton-Rochester relationship for Behn’s self-curation as a poet in the mid-1680s, as well as for Wharton’s own poetic development and literary ambitions.
SPECIAL ISSUE INTRODUCTION The Many Faces of Habeas Corpus in the American West
Authors: Jagodinsky Katrina 
Published: January 2025

Abstract
This introduction to a special issue offers a broad outline of habeas corpus historiography and explains the historical significance of that legal mechanism for people throughout the American West. It also explains the links between the special issue’s three articles—by Katrina Jagodinsky, Matthew Villeneuve, and Cory James Young—about women’s resistance to gendered violence, Indigenous families challenging federal Indian boarding school confinement, and Black minors’ ongoing vulnerability to coercive labor in the late nineteenth century.
Tranexamic dosing for major joint arthroplasty in adult patients with chronic kidney disease: A pharmacokinetic study and new dosing regimen.
Authors: Yang Qi , He Jim , Peng H. Benson , Wen Binyu , Idestrup Christopher , Ravi Bheeshma , Murnaghan John , McCarron Aaron , Hadley Hana , Shin Hansoo , Kaustov Lilia , Wong Jeremy , Lin Yulia , Choi Stephen , Orser Beverley A. , Van der Vyver Martin , Safa Ben , Pang K. Sandy , Jerath Angela 
Published: January 2025

Background:
Tranexamic acid is an anti-fibrinolytic agent routinely used during hip and knee joint replacement surgery to minimize bleeding. Chronic kidney disease is a common chronic health problem seen among adults requiring major arthroplasty surgery. Tranexamic acid is renally cleared and may accumulate in chronic kidney disease. Optimal tranexamic acid dosing and dose adjustment for chronic kidney disease patients needing major arthroplasty is unknown. The objective of this study was to serially measure plasma tranexamic acid concentrations in patients with varied kidney function undergoing hip or knee replacement surgery for population pharmacokinetic modelling and to guide new dosing recommendations.

Methods:
Prospective cohort study enrolled 21 adults undergoing hip or knee replacement surgery between June 2020 – September 2022. Based on estimated glomerular filtration rate (eGFR), patients were stratified into good (≥ 60 mL/min/1.73 m2) and poor (< 60 mL/min/1.73 m2) renal function. Serial blood samples were taken to measure plasma tranexamic acid concentration levels (primary outcome) after an intravenous tranexamic acid 20 mg/kg bolus dose post anesthesia induction. Secondary clinical outcomes included adverse events (thromboembolic events, seizures), red cell transfusion, mortality, length of hospital stay. Analyses used curve stripping and population pharmacokinetic modelling and simulation.

Results:
Plasma tranexamic acid concentration levels were higher in patients with poor renal function and clearance compared to good renal function. Population pharmacokinetic modelling tested various tranexamic acid bolus and maintenance infusion regimens. Simulations revealed single bolus tranexamic acid administration leads to rapid rise and decline in plasma concentrations. We identified that plasma tranexamic acid levels of 50-75 mg/L were maintained for approximately 4 hours using a tranexamic acid bolus infusion of 15 mg/kg over 15 min together with a maintenance infusion of 7.5 mg/kg/h or 5 mg/kg/h for 2 hours for the good and poor renal function groups, respectively. There was no difference in secondary outcomes.

Conclusion:
Using population pharmacokinetic modelling and simulation, we recommend a new dosing regimen to optimize the anti-fibrinolytic effect of tranexamic acid and avoid excessive dosing.
The Representation of Wellness Programs in Plastic Surgery Residency
Authors: Schlidt Kevin , Hricz Nicholas , El-Mallah Jessica , Waldron Olivia , Karwoski Allison , Rasko Yvonne 
Published: January 2025

Background:
Plastic surgery residency comprises a significant portion of early adulthood. The difficulties of residency are well documented, particularly with the impact on wellness and risk of burnout. Structured wellness programs, mentorship, social support, and autonomy can decrease residency burnout. This study looked at how plastic surgery program websites and GME websites represent wellness and support programs between both integrated and independent plastic surgery residencies.

Methods:
A cross-sectional analysis of US plastic surgery residency programs was performed during the month of April 2024. The authors conducted a systematic content analysis on the available websites of these residency websites, GME websites, and associated programs’ Instagram and X (formally Twitter) pages. Data points included (1) mention of wellness on the program website, (2) vacation time mentioned on the website, (3) protected time available, (4) spouse support options, (5) day care options, (6) connections with mentors, (7) images of social events on the website, and (8) images of social events on Instagram. Data were compiled and analyzed in JASP (JASP Team [2024]. JASP [version 0.18.3; computer software]) as well as Microsoft Excel. Categorical variables were compared using binomial tests and chi-squared tests. Statistical significance was defined a P value less than or equal to 0.05.

Results:
The majority of plastic surgery residencies did not discuss or describe their wellness programs on their official website, regardless of program size. Similar results were displayed when searching for spousal support and daycare. GME websites were more comprehensive than the program websites but still showed significant discrepancies with vacation policies and day care. Mentorship was mentioned in under half of all plastic surgery residencies. Integrated programs were more likely to display social events on Instagram when compared with independent programs.

Conclusions:
Plastic surgery residencies do not provide evidence of existing wellness programs on their program websites. Although a lack of public information on wellness programs does not mean they do not exist, this could easily be mitigated by providing more comprehensive information on both GME and program websites.
Relating digitalization and quality management in health care organizations: A systematic review
Authors: Rego Kerstin , Petzold Thomas 
Published: January 2025

Background
Quality management has been established in health care organizations as an important management function for internal quality measurement and external quality reporting. Digitalization processes have recently gained momentum with uncertain outcomes for health care organizations, quality, and the role of quality management.

Purpose
We conduct a systematic review to answer the questions of how the introduction of digital technologies affects quality management as a management function, how quality management is affecting digitalization, which quality management topics are addressed, and which competencies are needed during digitalization.

Methods
Four databases were searched from 2000 to January 2022. Both empirical and conceptual articles reporting on digital technologies and quality management as a management function, quality reporting, or risk management were included. The studies included were analyzed based on the PICOS and PRISMA approaches.

Results
A total of 20 out of 662 articles met the inclusion criteria. Results show that both quality management as a management function as well as the digitalization of quality managements’ own work processes are barely visible in the existing research. Only parts of the core tasks of quality management are discussed in connection with digitalization. Core competencies relevant for digitalization processes and quality management are identified.

Practice Implications
Quality managers require knowledge of digital technologies in order to develop and implement them to support their own work processes and the work processes of health care organizations in general. Currently, research is not guiding this process, which makes it important for quality managers to be able to access local knowledge. In addition, professional associations should develop skill catalogs for quality management education.
Retained lens fragment causing anterior uveitis four years after successful phacoemulsification
Authors: Shoukry Mira , Lopez-Ruiz Andrea , Patel Dharmendra , Shusko Alexander 
Published: January 2025

Introduction:
Existing literature has detailed occurrences of retained cataract lens fragments identified days to weeks after cataract surgery. However, lens fragments in the anterior chamber remaining asymptomatic for several years are extremely rare, thus remaining a diagnostic challenge. A complex case of a retained lens fragment causing anterior uveitis 4 years after phacoemulsification is presented.

Patient and Clinical Findings:
A 76-year-old woman presented with a chief concern of right eye pain, photosensitivity, and blurred vision after head trauma.

Diagnosis, Intervention, and Outcomes:
Diagnostic imaging ruled out the presence of orbital fracture or globe deformity leading to an initial diagnosis of traumatic iritis. Initial management with topical corticosteroids did not improve symptoms. Subsequent slit lamp examination revealed a small cataract lens fragment in the anterior chamber leading to a diagnosis of anterior uveitis secondary to the retained lens. Anterior chamber washout was performed with successful removal of the fragment, and the patient reported resolution of pain and photosensitivity postoperatively.

Conclusions:
Owing to its rarity, diagnostic and treatment standards for retained cataract lens fragments have not yet been sufficiently explored. This case suggests that head trauma may be a precipitating event causing delayed onset of symptoms. Cataract lens retention should be considered in patients presenting with uveitis years after cataract surgery.
Work Disability Prevention and Management
Authors: Kertay Les , Caruso Garson M. , Baker Nancy A. , Christian Jennifer H. , Cook Jerald L. , Das Rajiv , Goertz Michael , McKenzie Judith Green , Martin Douglas W. , Melhorn J. Mark , Mohammad Amir , Pransky Glenn , Warren Pamela A. , Mandel Steven , Harris Jeffrey S. , Hegmann Kurt T. ,   ACOEM Evidence-based Practice Work Disability and Prevention and Management Panel
Published: January 2025

Abstract

Objective: This abbreviated version of the American College of Occupational and Environmental Medicine’s (ACOEM) Work Disability Prevention and Management Guideline reviews the available evidence and provides recommendations to clinicians regarding interventions to help patients remain at or return to work.

Methods: Systematic literature reviews were conducted. Studies were graded and evidence tables were created, with involvement of a multidisciplinary expert panel that evaluated the evidence and finalized recommendations for all clinical questions. Extensive peer review was performed. Consensus recommendations were formulated when evidence was lacking.

Results: Evidence-based recommendations have been developed to guide work disability prevention and management.

Conclusion: Clinicians should utilize quality evidence in determining treatment methods to prevent and alleviate work disability for workers.