bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Medicaid Expansion Under the Affordable Care Act on Receipt of Surgery for Breast Cancer
Authors: Elmore Leisha C. , Li Meng , Lin Heather , Shen Yu , Shaitelman Simona F. , Babiera Gildy , Tamirisa Nina , Bedrosian Isabelle 
Published: August 2022

Objective:
To determine whether Medicaid expansion under the 2010 Affordable Care Act affected rates of breast cancer surgery.

Background:
Data regarding the impact of Medicaid expansion on access to surgical treatment of breast cancer are limited.

Methods:
Patients in the National Cancer Database diagnosed with non-metastatic breast cancer between January 1, 2010 and December 31, 2017 and residing in a state that expanded Medicaid in January 2014 or in a state that opted out of expansion were included. A quasi-experimental, difference-in-differences (DID) approach was used to assess rate of omission of surgical treatment.

Results:
Of 624,237 patients diagnosed with invasive breast cancer, 24,728 (4%) patients did not undergo surgical treatment. Overall, no significant differences in rates of omission of surgery over time were seen based on Medicaid expansion status. Significant findings were noted based on patient residential location. In rural areas, Medicaid expansion was associated with lower rates of omission of surgery (adjusted DID −2.47%, 95% confidence interval [CI] −4.01% to −0.94%; P = 0.002). In urban area, rates of omission of surgery increased over time for both groups, but the relative increase was lower in expansion states (adjusted DID −0.72%, 95% CI −1.25% to −0.20%; P = 0.007). In metro areas, changes in rates of surgery over time were comparable across expansion and non-expansion states (adjusted DID −0.08%, 95% CI −0.32% to 0.16%; P = 0.512).

Conclusions:
Medicaid expansion had no measurable effect on the receipt of surgery for breast cancer in the overall cohort. Medicaid expansion was associated with higher rates of surgery in rural areas, representing the minority of the population.
Risk of Acute Kidney Injury and Fracture-Related Infection After Antibiotic Prophylaxis With Piperacillin-Tazobactam in Open Fractures
Authors: McMurtrie Thompson , Cone Ryan J. , Mihas Alexander K. , Patch David A. , McGwin Gerald , Spitler Clay A. 
Published: August 2022

Objectives:
To evaluate the effects of prophylactic piperacillin-tazobactam (PT) on inpatient acute kidney injury (AKI) and fracture-related infection (FRI) in patients with open fractures.

Setting:
The study was conducted at a Level 1 trauma center.

Patients:
We reviewed 358 Gustilo–Anderson type II and III open fractures at our institution from January 2013 to December 2017.

Intervention:
Administration of PT (the PT group) or antibiotics other than PT (the historical control group) during the first 48 hours of arrival for open fracture antibiotic prophylaxis.

Main Outcome Measurements:
The main outcome measurements were rates of inpatient AKI and FRI within six months after definitive fixation.

Results:
There were 176 patients in the PT group and 182 patients in the historical control group. The PT group had worse American Society of Anesthesiologists class (P = 0.004) and injury severity scores (P < 0.001), a higher average number of debridements before closure/coverage (P = 0.043), and higher rates of gross soil contamination (P = 0.049) and staged procedures (P = 0.008) compared with the historical control group.
There was no difference in the rate of AKI between the PT and historical control groups (5.7% vs. 2.7%, P = 0.166) nor when stratified by Gustilo–Anderson fracture classification (type II: 5.8% vs. 3.6%, P = 0.702; type III: 5.6% vs. 2.0%, P = 0.283). There was no significant difference in the rate of FRI between the PT and historical control groups (23.6% vs. 19.6%, P = 0.469).

Conclusion:
The use of PT in prophylactic antimicrobial treatment in patients with Gustilo–Anderson type II and III open fractures does not increase the rate of AKI or FRI. We believe PT can be used as an effective monotherapy in these patients without an increased risk of renal injury, but future investigations are necessary.

Level of Evidence:
Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Integrating new oral selective oestrogen receptor degraders in the breast cancer treatment
Authors: Garcia-Fructuoso Isabel , Gomez-Bravo Raquel , Schettini Francesco 
Published: August 2022

Purpose of review
Oral SERDs are under extensive development to overcome fulvestrant main limitations, including intramuscular-only formulation and poor performance in early-stage hormone receptor-positive (HR+)/HER2-negative breast cancer. This review summarizes the most relevant evidence published so far and envisions the potential integration of oral SERDs in the therapeutic algorithm of HR+/HER2-negative metastatic breast cancer (MBC).

Recent findings
Amcenestrant and giredestrant, two of the most promising oral SERDs, recently failed to show a significant improvement in progression-free survival (PFS) in pivotal trials. Conversely, elacestrant demonstrated significant PFS superiority over standard-of-care endocrine therapy (aromatase inhibitors or fulvestrant) in MBC. Additionally, it did not show unusual side effects observed with other oral SERDs, like bradycardia, hematotoxicity and vision impairment, and proved to be effective also in case of ESR1-mutant endocrine-resistant breast cancer. Combination trials of oral SERDs with target agents, such as CDK4/6-inhibitors, are ongoing. Finally, some window-of-opportunity trials showed promising on-target activity in early-stage for this drug class.

Summary
Promising results from early-phase trials are not translating into sufficient clinical benefit in pivotal trials of main oral SERDs in monotherapy, except for elacestrant. Whether oral SERDs might become the backbone for combination strategies in MBC or the preferred (neo)adjuvant endocrine agents is under evaluation.
Circadian effect of time of anaesthesia on postoperative outcomes in major elective and urgent intervention: a secondary analysis of the Peri-interventional Outcome Study in the Elderly (POSE)
Authors: Hoogma Danny Feike , Al Tmimi Layth , Fieuws Steffen , Tournoy Jos , Kowark Ana , Rossaint Rolf , Coburn Mark , Rex Steffen 
Published: August 2022

BACKGROUND
A recent prospective study reported a decrease in postoperative mortality when cardiac surgery was started in the afternoon instead of in the morning. In contrast, several large retrospective analyses have not confirmed this finding. Larger prospective studies are required to elucidate the effects of circadian rhythm on postoperative outcomes.

OBJECTIVE
To identify any relation between starting time of anaesthesia/surgery and postoperative outcomes in patients aged 80 years or older to aid in clinical decision making with regard to scheduling surgery.

DESIGN
A multivariable model with a priori defined confounders was constructed to evaluate the impact of anaesthesia starting time on hospital length of stay and postoperative complications.

SETTING
A European multicentre, observational study of outcomes after geriatric anaesthesia from October 2017 to December 2018.

PATIENTS
Patients aged 80 years or older having major elective or urgent intervention with anaesthesia starting time between 7 a.m. and 7 p.m.

MAIN OUTCOME MEASURE
Primary outcome measure was the difference in hospital length of stay after any major elective or urgent morning or afternoon intervention.

RESULTS
We included 3551 patients of whom 2592 had an intervention starting in the morning (7 a.m. to 1 p.m.). These patients, compared with those with interventions in the afternoon (1 p.m. to 7 p.m.), were slightly younger, were less frail but had a longer duration of the intervention. Hospital length of stay or postoperative complications were not different between morning or afternoon interventions. Multivariable analysis showed no impact of time of anaesthesia (morning vs. afternoon) on hospital length of stay or postoperative complications, hazard ratio of 1.03 (95% CI 0.94 to 1.12) and odds ratio of 1.13 (95% CI 0.92 to 1.39), respectively.

CONCLUSION
Our results do not support the hypothesis of circadian effects on postoperative outcomes for elective and urgent major interventions in patients at least 80 years of age.

TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03152734
Opioid deprescribing in patients with chronic noncancer pain: a systematic review of international guidelines
Authors: Hamilton Melanie , Kwok Wing S. , Hsu Arielle , Mathieson Stephanie , Gnjidic Danijela , Deyo Richard , Ballantyne Jane , Von Korff Michael , Blyth Fiona , Lin Chung-Wei Christine 
Published: August 2022

Abstract
In response to the overuse of prescription opioid analgesics, clinical practice guidelines encourage opioid deprescribing (ie, dose reduction or cessation) in patients with chronic noncancer pain. Therefore, this study evaluated and compared international clinical guideline recommendations on opioid deprescribing in patients with chronic noncancer pain. We searched PubMed, EMBASE, PEDro, National Institute for Health and Care Excellence (United Kingdom), and MAGICapp databases from inception to June 4, 2021, with no language or publication restrictions. In addition, we searched the National Guideline Clearinghouse and International Guideline Network databases from inception to December 2018. Two independent reviewers conducted the initial title and abstract screening. After discrepancies were resolved through discussion, 2 independent reviewers conducted the full-text screening of each potentially eligible reference. Four independent reviewers completed the prepiloted, standardized data extraction forms of each included guideline. Extracted information included bibliographical details; strength of recommendations; and the outcomes, such as when and how to deprescribe, managing withdrawal symptoms, additional support, outcome monitoring, and deprescribing with coprescription of sedatives. A narrative synthesis was used to present the results. This study found that clinical practice guidelines agree on when and how to deprescribe opioid analgesics but lack advice on managing a patient's withdrawal symptoms, outcome monitoring, and deprescribing with coprescription of sedatives. Quality assessment of the guidelines suggests that greater discussion on implementation and dissemination is needed.
The Beirut ammonium nitrate blast: A multicenter study to assess injury characteristics and outcomes
Authors: Al-Hajj Samar , Farran Sarah H. , Zgheib Hady , Tfaily Mohamad Ali , Halaoui Adham , Wehbe Sarah , Karam Stephanie , Fadlallah Yaser , Fahd Fares , Toufaili Lana , Arjinian Sebouh , AL-Zaghrini Elie , Al Hariri Moustafa , El Hussein Mahmoud , Souaiby Naji , Mowafi Hani , Mufarrij Afif Jean 
Published: August 2022

BACKGROUND
Blasts incidents impose catastrophic aftermaths on populations regarding casualties, sustained injuries, and devastated infrastructure. Lebanon witnessed one of the largest nonnuclear chemical explosions in modern history—the August 2020 Beirut Port blast. This study assesses the mechanisms and characteristics of blast morbidity and mortality and examines severe injury predictors through the Injury Severity Score.

METHODS
A retrospective, multicenter cross-sectional study was conducted. Data of trauma patients presenting to five major acute-care hospitals in metropolitan Beirut up to 4 days following the blast were collected in a two-stage process from patient hospital chart review and follow-up phone calls.

RESULTS
A total of 791 patients with a mean age of 42 years were included. The mean distance from the blast was 2.4 km (SD, 1.9 km); 3.1% of victims were in the Beirut Port itself. The predominant mechanism of injury was being struck by an object (falling/projectile) (293 [37.0%]), and the most frequent site of injury was the head/face (209 [26.4%]). Injury severity was low for 548 patients (71.2%), moderate for 62 (8.1%), and severe/critical for 27 (3.5%). Twenty-one deaths (2.7%) were recorded. Significant serious injury predictors (Injury Severity Score, >15) were sustaining multiple injuries (odds ratio [OR], 2.62; p = 0.005); a fracture (OR, 5.78; p < 0.001); primary blast injuries, specifically a blast lung (OR, 18.82; p = 0.001), concussion (OR, 7.17; p < 0.001), and eye injury (OR, 8.51; p < 0.001); and secondary blast injuries, particularly penetrating injuries (OR, 9.93; p < 0.001) and traumatic amputations (OR, 13.49; p = 0.01). Twenty-five percent were admitted to the hospital, with 4.6% requiring the intensive care unit. At discharge, 25 patients (3.4%) had recorded neurologic disability.

CONCLUSION
Most injuries sustained by the blast victims were minor. Serious injuries were mostly linked to blast overpressure and projectile fragments. Understanding blast injuries characteristics, their severity, and management is vital to informing emergency services, disaster management strategies, hospital preparedness, and, consequently, improving patient outcomes.

LEVEL OF EVIDENCE
Prognostic and Epidemiologic; Level III.
Surgical stabilization of rib fractures versus nonoperative treatment in patients with multiple rib fractures following cardiopulmonary resuscitation: an international, retrospective matched case-control study (CWIS-CPR)
Authors: Prins Jonne T.H. , Van Lieshout Esther M.M. , Eriksson Evert A. , Barnes Matthew , Blokhuis Taco J. , Caragounis Eva-Corina , Benjamin Christie D. , De Loos Erik R. , DeVoe William B. , Formijne Jonkers Henk A. , Kiel Brandon , Ko Huan-Jang , Marasco Silvana F. , Spanjersberg Willem R. , Su Ying-Hao , Summerhayes Robyn G. , Van Huijstee Pieter J. , Vermeulen Jefrey , Vos Dagmar I. , Verhofstad Michael H.J. , Wijffels Mathieu M.E. 
Published: August 2022

ABSTRACT

Background
The presence of six or more rib fractures or a displaced rib fracture due to cardiopulmonary resuscitation (CPR) has been associated with longer hospital and intensive care unit (ICU) length of stay. Evidence on the effect of surgical stabilization of rib fractures (SSRF) following CPR is limited. This study aimed to evaluate outcomes after SSRF versus nonoperative management in patients with multiple rib fractures after CPR.

Methods
An international, retrospective study was performed in patients who underwent SSRF or nonoperative management for multiple rib fractures following CPR between January 1, 2012 and July 31, 2020. Patients who underwent SSRF were matched to nonoperative controls by cardiac arrest location and cause, rib fracture pattern, and age. The primary outcome was ICU length of stay (LOS).

Results
Thirty-nine operatively treated patient were matched to 66 nonoperatively managed controls with comparable CPR-related characteristics. Patients who underwent SSRF more often had displaced rib fractures (n = 28, 72% vs. n = 31, 47%; p = 0.015) and a higher median number of displaced ribs (2, P25-P75 0-3 vs. 0, P25-P75 0-3; p = 0.014). SSRF was performed at a median of 5 days (P25-P75 3-8) after CPR. In the nonoperative group, a rib fixation specialist was consulted in 14 patients (21%). The ICU LOS was longer in the SSRF group (13 days, P25-P75 9-23 vs. 9 days, P25-P75 5-15; p = 0.004). Mechanical ventilator-free days, hospital LOS, thoracic complications, and mortality were similar.

Conclusion
Despite matching, those who underwent SSRF over nonoperative management for multiple rib fractures following CPR had more severe consequential chest wall injury and a longer ICU LOS. A benefit of SSRF on in-hospital outcomes could not be demonstrated.
A low consultation rate for rib fixation in the nonoperative group indicates that the consideration to perform SSRF in this population might be associated with other non-radiographic or injury-related variables.

Level of evidence
therapeutic study, level III
Clinical nomogram using novel CT based radiomics predicts survival in non-small cell lung cancer patients treated with SBRT
Authors: Somasundaram Eashwar , Wadhwa Raoul R. , Litzler Adam , Barker-Clarke Rowan , Qi Peng , Videtic Gregory , Stephans Kevin , Pennell Nathan A. , Raymond Daniel , Yang Kailin , Kattan Michael W. , Scott Jacob G. 
Published: August 2022

AbstractIntroductionImproved survival prediction and risk stratification in non-small cell lung cancer (NSCLC) would lead to better prognosis counseling, adjuvant therapy selection, and clinical trial design. We propose the PHOM (persistent homology) score, the radiomic quantification of solid tumor topology, as a solution.MethodsPatients diagnosed with stage I or II NSCLC primarily treated with stereotactic body radiation therapy (SBRT) were selected (n= 554). The PHOM score was calculated on each patient’s pre-treatment CT scan (10/2008 to 11/2019). PHOM score, age, sex, stage, Karnofsky Performance Status (KPS), Charlson-Comorbidity Index (CCI), and post-SBRT chemotherapy were predictors in the Cox proportional hazards models for overall and cancer-specific survival. Patients were split into high and low PHOM score groups compared using Kaplan-Meier curves for overall survival and cumulative incidence curves for cause specific death. Finally, we generated a validated nomogram to predict overall survival, publicly available athttps://eashwarsoma.shinyapps.io/LungCancerTDATest/.ResultsPHOM score was a significant predictor for overall survival (HR: 1.17, 95% CI: 1.07−1.28) and was the only significant predictor for cancer-specific survival (1.31, 95% CI: 1.11−1.56) in the multivariable Cox model. The median survival for the high PHOM group was 29.2 months (95% CI: 23.6−34.3), which was significantly worse compared to the low PHOM group (45.4 months, 95% CI: 40.1−51.8,p <0.001). The high PHOM group had a significantly greater chance of cancer-specific death at post treatment month 65 (0.244, 95%CI: 0.192−0.296) compared to the low PHOM group (0.171, 95% CI: 0.123−0.218,p= 0.029).ConclusionsThe PHOM score is associated with cancer-specific survival and predictive of overall survival. Our developed nomogram can be used to inform clinical prognosis and assist in making post-SBRT treatment considerations.
A bioluminescence-basedex vivoburn wound model for real-time assessment of novel antibacterial compounds
Authors: De Maesschalck V. , Gutiérrez D. , Paeshuyse J. , Briers Y. , Vande Velde G. , Lavigne R. 
Published: August 2022

AbstractThe silent pandemic of antibiotic resistance is thriving, prompting the urgent need for the development of new antibacterial drugs. However, within the preclinical pipeline,in vitroscreening conditions can differ significantly from the finalin vivosettings. To bridge the gap betweenin vitroandin vivoassays, we developed a pig skin-based bioluminescentex vivoburn wound infection model, enabling real-time assessment of antibacterials in a longitudinal, non-destructive manner. We provide a proof-of-concept forA. baumanniiNCTC13423, a multidrug-resistant clinical isolate, which was equipped with theluxCDABEoperon as a reporter using a Tn7-based tagging system. This bioluminescence model provided a linear correlation between the number of bacteria and a broad dynamic range (104to 109CFU). This longitudinal model was subsequently validated using a fast-acting enzybiotic as an antibacterial. Since this model combines a realistic, clinically relevant yet strictly controlled environment with real-time measurement of bacterial burden, we put forward thisex vivomodel as a valuable tool to assess the preclinical potential of novel antibacterial compounds.Summary statementHere, we demonstrate the potential of a bioluminescence-basedex vivomodel for the longitudinal assessment of antibacterials. Moreover, we also provide a proof-of-concept with an engineered lysin.
A genome-scale metabolic model of Drosophila melanogaster for integrative analysis of brain diseases
Authors: Cesur Müberra Fatma , Patil Kiran Raosaheb , Çakır Tunahan 
Published: August 2022

AbstractHigh conservation of the disease-associated genes between fly and human facilitates the common use of Drosophila melanogaster to study metabolic disorders under controlled laboratory conditions. However, metabolic modeling studies are highly limited for this organism. We here report a comprehensively curated genome-scale metabolic network model of Drosophila using an orthology-based approach. The gene coverage and metabolic information of the orthology-based draft model were expanded via Drosophila-specific KEGG and MetaCyc databases, with several curation steps to avoid metabolic redundancy and stoichiometric inconsistency. Further, we performed literature-based curations to improve gene-reaction associations, subcellular metabolite locations, and updated various metabolic pathways including cholesterol metabolism. The performance of the resulting Drosophila model, termed iDrosophila1 (8,230 reactions, 6,990 metabolites, and 2,388 genes), was assessed using flux balance analysis in comparison with the other currently available fly models leading to superior or comparable results. We also evaluated transcriptome-based prediction capacity of the iDrosophila1, where differential metabolic pathways during Parkinson’s disease could be successfully elucidated. Overall, iDrosophila1 is promising to investigate systems-level metabolic alterations in response to genetic and environmental perturbations.
In vivo and In vitro Characterization of the ClpC AAA+ ATPase of Chlamydia trachomatis
Authors: Pan Stefan , Jensen Aaron A. , Wood Nicholas A. , Henrichfreise Beate , Brötz-Oesterhelt Heike , Fisher Derek J. , Sass Peter , Ouellette Scot P. 
Published: August 2022

AbstractBacterial AAA+ unfoldases are crucial for bacterial physiology by recognizing specific substrates and, typically, unfolding them for degradation by a proteolytic component. The caseinolytic protease (Clp) system is one example where a hexameric unfoldase (e.g., ClpC) interacts with the tetradecameric proteolytic core ClpP. Unfoldases can have both ClpP-dependent and ClpP-independent roles in protein homeostasis, development, virulence, and cell differentiation. ClpC is an unfoldase predominantly found in Gram-positive bacteria and mycobacteria. Intriguingly, the obligate intracellular Gram-negative pathogen Chlamydia, an organism with a highly reduced genome, also encodes a ClpC ortholog, implying an important function for ClpC in chlamydial physiology. Here, we used a combination of in vitro and in vivo approaches to gain insight into the function of chlamydial ClpC. ClpC exhibits intrinsic ATPase and chaperone activities, with a primary role for the Walker B motif in the first nucleotide binding domain (NBD1). Furthermore, ClpC binds ClpP1P2 complexes via ClpP2 to form the functional protease ClpCP2P1 in vitro, which degraded arginine-phosphorylated β-casein. In vivo experiments confirmed that higher order complexes of ClpC are present in chlamydial cells. Importantly, the in vivo data further revealed severe negative effects of both overexpression and depletion of ClpC in Chlamydia as revealed by a significant reduction in chlamydial growth. Here again, NBD1 was critical for ClpC function. Hence, we provide the first mechanistic insight into the molecular and cellular function of chlamydial ClpC, which supports its essentiality in Chlamydia. ClpC is, therefore, a potential novel target for the development of anti-chlamydial agents.SignificanceChlamydia trachomatis is an obligate intracellular pathogen and the world’s leading cause of preventable infectious blindness and bacterial sexually transmitted infections. Due to the high prevalence of chlamydial infections along with negative effects of current broad-spectrum treatment strategies, new anti-chlamydial agents with novel targets are desperately needed. In this context, bacterial Clp proteases have emerged as promising new antibiotic targets, since they often play central roles in bacterial physiology and, for some bacterial species, are even essential for survival. Here, we report on the chlamydial AAA+ unfoldase ClpC, its functional reconstitution and characterization, individually and as part of the ClpCP2P1 protease, and establish an essential role for ClpC in chlamydial growth and intracellular development, thereby identifying ClpC as a potential target for anti-chlamydial compounds.