bluuebunny/crossref_metadata_2025_split huggingface dataset:
Progressive Lung Injury, Inflammation, and Fibrosis in Rats Following Inhalation of Sulfur Mustard
Authors: Malaviya Rama , Abramova Elena V , Rancourt Raymond C , Sunil Vasanthi R , Napierala Marta , Weinstock Daniel , Croutch Claire R , Roseman Julie , Tuttle Rick , Peters Eric , Casillas Robert P , Laskin Jeffrey D , Laskin Debra L 
Published: September 2020

AbstractSulfur mustard (SM) inhalation causes debilitating pulmonary injury in humans which progresses to fibrosis. Herein, we developed a rat model of SM toxicity which parallels pathological changes in the respiratory tract observed in humans. SM vapor inhalation caused dose (0.2–0.6 mg/kg)-related damage to the respiratory tract within 3 days of exposure. At 0.4–0.6 mg/kg, ulceration of the proximal bronchioles, edema and inflammation were observed, along with a proteinaceous exudate containing inflammatory cells in alveolar regions. Time course studies revealed that the pathologic response was biphasic. Thus, changes observed at 3 days post-SM were reduced at 7–16 days; this was followed by more robust aberrations at 28 days, including epithelial necrosis and hyperplasia in the distal bronchioles, thickened alveolar walls, enlarged vacuolated macrophages, and interstitial fibrosis. Histopathologic changes were correlated with biphasic increases in bronchoalveolar lavage (BAL) cell and protein content and proliferating cell nuclear antigen expression. Proinflammatory proteins receptor for advanced glycation end product (RAGE), high-mobility group box protein (HMGB)-1, and matrix metalloproteinase (MMP)-9 also increased in a biphasic manner following SM inhalation, along with surfactant protein-D (SP-D). Tumor necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS), inflammatory proteins implicated in mustard lung toxicity, and the proinflammatory/profibrotic protein, galectin (Gal)-3, were upregulated in alveolar macrophages and in bronchiolar regions at 3 and 28 days post-SM. Inflammatory changes in the lung were associated with oxidative stress, as reflected by increased expression of heme oxygenase (HO)-1. These data demonstrate a similar pathologic response to inhaled SM in rats and humans suggesting that this rodent model can be used for mechanistic studies and for the identification of efficacious therapeutics for mitigating toxicity.
An update on gout diagnosis and management for the primary care provider
Authors: Mbuyi Nadine , Hood Catherine 
Published: September 2020

Abstract:
Gout is the most common inflammatory arthritis in the US, affecting 3.9% of the population. Although many effective gout therapies are available for acute flares and chronic management, it is suboptimally treated worldwide, and recurrent gout flares can cause significant pain and irreversible joint damage.
Declining Medicare Reimbursement in Orthopaedic Trauma Surgery: 2000–2020
Authors: Haglin Jack M. , Lott Ariana , Kugelman David N. , Konda Sanjit R. , Egol Kenneth A. 
Published: September 2020

Objectives:
To evaluate monetary trends in government (Medicare) reimbursement rates for 20 commonly used orthopedic trauma surgical procedures over a 20-year period.

Methods:
The Physician Fee Schedule Look-Up Tool from the Centers for Medicare & Medicaid Services was queried for the 20 common Current Procedural Terminology (CPT) codes in orthopaedic trauma, and reimbursement data were extracted. All monetary data were adjusted for inflation to 2020 US dollars (USD) using changes to the US Consumer Price Index. Both the average annual and the total percentage change in reimbursement and in Relative Value Units were calculated for all included procedures.

Results:
After adjusting for inflation, the average reimbursement for all procedures decreased by 30.0% from 2000 to 2020. Total Relative Value Units during this time increased by 4.4% on average. Procedures about the foot and ankle demonstrated the greatest decrease in the mean adjusted reimbursement at −42.6%, whereas procedures about the shoulder and upper extremity demonstrated the smallest mean decrease at 23.7% during the study period. From 2000 to 2020, the adjusted reimbursement rate for all included procedures decreased by an average of 1.5% each year.

Conclusion:
To the best of our knowledge, this is the first study to comprehensively evaluate trends in procedural Medicare reimbursement for orthopaedic trauma. When adjusted for inflation, Medicare reimbursement for included procedures has steadily decreased from 2000 to 2020. Increased awareness and consideration of these trends will be important for policy makers, hospitals, and surgeons to assure continued access to meaningful surgical orthopaedic trauma care in the United States.
The Effectiveness and Safety of Direct Oral Anticoagulants Following Lower Limb Fracture Surgery: A Systematic Review and Meta-analysis
Authors: Wæver Daniel , Lewis Daniel , Saksø Henrik , Borris Lars C. , Tarrant Seth , Thorninger Rikke 
Published: September 2020

Objectives:
Venous thromboembolism (VTE) is a well-established complication after many orthopaedic injuries, such as hip and lower limb fractures. The use of direct oral anticoagulants (DOACs, previously termed novel oral anticoagulants) is well-established as thromboprophylaxis after major elective orthopaedic surgery, but not in the nonelective setting. The aim of this study was to investigate the effectiveness and safety of DOACs after nonelective lower limb fracture surgery.

Data Sources:
A systematic literature search of the MEDLINE, EMBASE, CINAHL, and CENTRAL databases was conducted. No limitation was placed on publication date, with only manuscripts printed in English were eligible.

Study Selection:
Included studies were either randomized controlled trials or prospective and retrospective comparative studies. Included studies compared DOACs to conventional methods of thromboprophylaxis in the postoperative period after surgical management of lower limb fractures.

Data Extraction:
Outcomes included VTE, bleeding, wound complications, mortality, and adverse events. Eight studies met inclusion criteria, of which 7 compared direct factor Xa inhibitors (XaIs) with conventional VTE prophylaxis and one study compared a direct thrombin inhibitor with conventional VTE prophylaxis.

Data Synthesis:
Revman 5.3 (Nordic Cochrane Centre, Denmark) was used to complete the meta-analysis and generate forest plots.

Conclusions:
XaIs were shown to have lower rates of deep vein thrombosis (Odds ratio 0.59; 95% confidence interval, 0.46–0.76; P < 0.0001) and less pharmacologically attributable adverse events (Odds ratio 0.62; 95% confidence interval, 0.46–0.82; P = 0.0007). There was difference between DOACs and conventional VTE prophylaxis regarding mortality, PE, symptomatic deep vein thrombosis, or bleeding events. The results generally support the use of DOACs for VTE prophylaxis after nonelective lower limb fracture surgery, such after hip fracture. The results more strongly support the use of XaIs; however, more evidence is needed to fully assess DOACs' role in clinical practice.

Level of Evidence:
Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.
Advanced Respiratory Support in the Contemporary Cardiac ICU
Authors: Metkus Thomas S. , Miller P. Elliott , Alviar Carlos L. , Baird-Zars Vivian M. , Bohula Erin A. , Cremer Paul C. , Gerber Daniel A. , Jentzer Jacob C. , Keeley Ellen C. , Kontos Michael C. , Menon Venu , Park Jeong-Gun , Roswell Robert O. , Schulman Steven P. , Solomon Michael A. , van Diepen Sean , Katz Jason N. , Morrow David A. 
Published: September 2020

Objectives:
The medical complexity and critical care needs of patients admitted to cardiac ICUs are increasing, and prospective studies examining the underlying cardiac and noncardiac diagnoses, the management strategies, and the prognosis of cardiac ICU patients with respiratory failure are needed.

Design:
Prospective cohort study.

Setting:
The Critical Care Cardiology Trials Network is a research collaborative of cardiac ICUs across the United States and Canada.

Patients:
We included all medical cardiac ICU admissions at 25 cardiac ICUs during two consecutive months annually at each center from 2017 to 2019.

Measurements:
We evaluated the use of advanced respiratory therapies including invasive mechanical ventilation, noninvasive ventilation, and high-flow nasal cannula versus no advanced respiratory support across admission diagnoses and the association with in-hospital mortality.

Main Results:
Of 8,240 cardiac ICU admissions, 1,935 (23.5%) were treated with invasive mechanical ventilation, 573 (7.0%) with noninvasive ventilation, and 281 (3.4%) with high-flow nasal cannula. Admitting diagnoses among those with advanced respiratory support were diverse including general medical problems in patients with heart disease as well as primary cardiac problems. In-hospital mortality was higher in patients who received invasive mechanical ventilation (38.1%; adjusted odds ratio, 2.53; 2.02–3.16) and noninvasive ventilation or high-flow nasal cannula (8.8%; adjusted odds ratio, 2.25; 1.73–2.93) compared with patients without advanced respiratory support (4.6%). Reintubation rate was 7.6%. The most common variables associated with respiratory insufficiency included heart failure, infection, chronic obstructive pulmonary disease, and pulmonary vascular disease.

Conclusions:
One-third of cardiac ICU admissions receive respiratory support with associated increased mortality. These data provide benchmarks for quality improvement ventures in the cardiac ICU, inform cardiac critical care training and staffing patterns, and serve as foundation for future studies aimed at improving outcomes.
Increased Dead Space Ventilation and Refractory Hypercapnia in Patients With Coronavirus Disease 2019: A Potential Marker of Thrombosis in the Pulmonary Vasculature
Authors: Oppenheimer Beno W. , Bakker Jan , Goldring Roberta M. , Teter Katherine , Green David L. , Berger Kenneth I. 
Published: September 2020

Objectives:
Mortality rates in intubated coronavirus disease 2019 patients remain markedly elevated. Some patients develop sudden refractory hypercapnia and hypoxemia not explained by worsening pulmonary parenchymal disease. This case series highlights clinical findings and management of coronavirus disease 2019 patients with refractory hypercapnia despite maximal/optimal ventilatory support. Hypercapnia could not be explained by worsening lung disease or other common factors, and thus, a pulmonary vascular etiology was suggested. The pillars of management were targeted to improve pulmonary vascular patency via aggressive anticoagulation and support right ventricular function.

Data Sources:
Four consecutive patients with confirmed coronavirus disease 2019 infection with sudden hypercapnia and hypoxemia were included.

Data Synthesis:
There was sequential development of: 1) severe hypercapnia attributable to marked elevation of dead space without radiographic changes; 2) concomitant coagulopathy manifest by an increase in d-dimer levels; 3) progressive shunt with consequent hypoxemia; and 4) right ventricular dysfunction. Management included extracorporeal Co
2 removal, direct thrombin inhibition, pulmonary vasodilators, and inotropic support. Marked improvement in Pao
2 allowed reduction in Fio
2 in all patients, extracorporeal Co
2 removal was discontinued in three patients over the ensuing 3 weeks, and one patient was discharged home.

Conclusions:
We speculate that thromboinflammation with pulmonary microvasculature occlusion leads to a sudden increase in dead space and shunt resulting in severe hypercapnia and hypoxemia in coronavirus disease 2019 patients. Early identification of these physiologic and clinical biomarkers could trigger the institution of therapies aiming to reverse the hypercoagulable state and support right ventricular function.
Comparison of the Safety and Efficacy of Foam Sclerotherapy With 1:2 Polidocanol to Air Ratio Versus 1:4 Ratio for the Treatment of Reticular Veins of the Lower Extremities
Authors: Hoss Elika , Kollipara Ramya , Boen Monica , Alhaddad Marwan , Goldman Mitchel P. 
Published: September 2020

BACKGROUND
Foam sclerotherapy is a common treatment of lower extremity reticular veins. The effect of different liquid–gas ratios on foam stability and efficacy has been controversial.

OBJECTIVE
To evaluate the use of 2 different polidocanol (POL) to air ratios for the treatment of reticular veins of the lower extremities.

METHODS AND MATERIALS
Patients with lower extremity reticular veins were randomized to foam sclerotherapy with POL mixed with 4 mL of room air for one lower extremity or 2 mL for the other lower extremity. All telangiectasias were treated with glycerin immediately after treatment of the reticular veins. Adverse events (AEs) and efficacy were evaluated by both subject and blinded investigator.

RESULTS
Thirty subjects completed the study. No statistically significant difference was seen in AEs between the 2 different POL to air ratios by subject questionnaire and blinded investigator scores at all time points. Subjects and blinded investigator reported a mean improvement between 0% and 50% at Day 21 and 26% to 75% at Day 90, which was not significantly different between groups.

CONCLUSION
Two different POL to air ratios, 1:2 versus 1:4, were similarly safe and efficacious for the treatment reticular veins of the lower extremities.
Development of a Simple Clinical Tool for Predicting Early Dropout in Cardiac Rehabilitation
Authors: Pack Quinn R. , Visintainer Paul , Farah Michel , LaValley Grace , Szalai Heidi , Lindenauer Peter K. , Lagu Tara 
Published: September 2020

Background:
Nonadherence to cardiac rehabilitation (CR) is common despite the benefits of completing a full program. Adherence might be improved if patients at risk of early dropout were identified and received an intervention.

Methods:
Using records from patients who completed ≥1 CR session in 2016 (derivation cohort), we employed multivariable logistic regression to identify independent patient-level characteristics associated with attending <12 sessions of CR in a predictive model. We then evaluated model discrimination and validity among patients who enrolled in 2017 (validation cohort).

Results:
Of the 657 patients in our derivation cohort, 318 (48%) completed <12 sessions. Independent risk factors for not attending ≥12 sessions were age <55 yr (OR = 0.23, P < .001), age 55 to 64 yr (OR = 0.35, P < .001), age ≥75 yr (OR = 0.64, P = .06), smoker within 30 d of CR enrollment (OR = 0.40, P = .001), low risk for exercise adverse events (OR = 0.54, P = .03), and nonsurgical referral diagnosis (OR = 0.66, P = .02). Our model predicted nonadherence risk from 23-90%, had acceptable discrimination and calibration (C-statistics = 0.70, Harrell's E50 and E90 2.0 and 3.6, respectively) but had fair validity among 542 patients in the validation cohort (C-statistic = 0.62, Harrell's E50 and E90 2.1 and 11.3, respectively).

Conclusion:
We developed and evaluated a single-center simple risk model to predict nonadherence to CR. Although the model has limitations, this tool may help clinicians identify patients at risk of early dropout and guide intervention efforts to improve adherence so that the full benefits of CR can be realized for all patients.
Exercise-Based Cardiac Rehabilitation Improves Cognitive Function Among Patients With Cardiovascular Disease
Authors: Moriarty Terence A. , Bourbeau Kelsey , Mermier Christine , Kravitz Len , Gibson Ann , Beltz Nicholas , Negrete Omar , Zuhl Micah 
Published: September 2020

Purpose:
To investigate the effects of cardiac rehabilitation (CR) exercise training on cognitive performance and whether the changes are associated with alterations in prefrontal cortex (PFC) oxygenation among patients with cardiovascular disease.

Methods:
Twenty (men: n = 15; women: n = 5) participants from an outpatient CR program were enrolled in the study. Each participant completed a cognitive performance test battery and a submaximal graded treadmill evaluation on separate occasions prior to and again upon completion of 18 individualized CR sessions. A functional near-infrared spectroscopy (fNIRS) device was used to measure left and right prefrontal cortex (LPFC and RPFC) oxygenation parameters (oxyhemoglobin [O2Hb], deoxyhemoglobin [HHb], total hemoglobin [tHb], and oxyhemoglobin difference [Hbdiff]) during the cognitive test battery.

Results:
Patients showed improvements in cardiorespiratory fitness (+1.4 metabolic equivalents [METs]) and various cognitive constructs. A significant increase in PFC oxygenation, primarily in the LPFC region, occurred at post-CR testing. Negative associations between changes in cognition (executive function [LPFC O2Hb: r = −0.45, P = .049; LPFC tHb: r = −0.49, P = .030] and fluid composite score [RPFC Hbdiff: r = −0.47, P = .038; LPFC Hbdiff: r = −0.45, P = .048]) and PFC changes were detected. The change in cardiorespiratory fitness was positively associated with the change in working memory score (r = 0.55, P = .016).

Conclusion:
Cardiovascular disease patients enrolled in CR showed significant improvements in multiple cognitive domains along with increased cortical activation. The negative associations between cognitive functioning and PFC oxygenation suggest an improved neural efficiency.
A Systematic Review of the Hematopoietic Acute Radiation Syndrome (H-ARS) in Canines and Non-human Primates: Acute Mixed Neutron/Gamma vs. Reference Quality Radiations
Authors: MacVittie Thomas J. , Farese Ann M. , Jackson William E. 
Published: September 2020

Abstract
A systematic review of relevant studies that determined the dose response relationship (DRR) for the hematopoietic (H) acute radiation syndrome (ARS) in the canine relative to radiation quality of mixed neutron:gamma radiations, dose rate, and exposure uniformity relative to selected reference radiation exposure has not been performed. The datasets for rhesus macaques exposure to mixed neutron:gamma radiation are used herein as a species comparative reference to the canine database. The selection of data cohorts was made from the following sources: Ovid Medline (1957–present), PubMed (1954–present), AGRICOLA (1976–present), Web of Science (1954–present), and US HHS RePORT (2002–present). The total number of hits across all search sites was 3,077. Several referenced, unpublished, non-peer reviewed government reports were unavailable for review. Primary published studies using canines, beagles, and mongrels were evaluated to provide an informative and consistent review of mixed neutron:gamma radiation effects to establish the DRRs for the H-ARS. Secondary and tertiary studies provided additional information on the hematologic response or the effects on hematopoietic progenitor cells, radiation dosimetry, absorbed dose, and organ dose. The LD50/30 values varied with neutron quality, exposure aspect, and mixed neutron:gamma ratio. The reference radiation quality varied from 250 kVp or 1–2 MeV x radiation and 60Co gamma radiation. A summary of a published review of a data set describing the DRR in rhesus macaques for mixed neutron:gamma radiation exposure in the H-ARS is included for a comparative reference to the canine dataset. The available evidence provided a reliable and extensive database that characterized the DRR for the H-ARS in canines and young rhesus macaques exposed to mixed neutron:gamma radiations of variable energy relative to 250 kVp, 1–2 MeV x radiation and 60Co gamma, and uniform and non-uniform total-body irradiation without the benefit of medical management. The mixed neutron:gamma radiation showed an energy-dependent RBE of ~ 1.0 to 2.0 relative to reference radiation exposure within both species. A marginal database described the DRR for the gastrointestinal (GI)-ARS. Medical management showed benefit in both species relative to the mixed neutron:gamma as well as exposure to reference radiation. The DRR for the H-ARS was characterized by steep slopes and relative LD50/30 values that reflected the radiation quality, exposure aspect, and dose rate over a range in time from 1956–2012.
Comparative Analysis of Safety and Efficacy of Topography-Guided Customized Cross-linking and Standard Cross-linking in the Treatment of Progressive Keratoconus
Authors: Sachdev Gitansha Shreyas , Ramamurthy Shreyas , B Soundariya , Dandapani Ramamurthy 
Published: September 2020

Purpose:
To compare the safety and efficacy of topography-guided customized corneal cross-linking (PiXL) with standard cross-linking (CXL) for the treatment of progressive keratoconus.

Methods:
In a prospective interventional analysis, the eyes of patients with progressive keratoconus underwent standard cross-linking (homogenous 9-mm ultraviolet-A irradiation of 9 mW/cm2 delivering a total fluence of 5.4J/cm2) versus topography-guided customized cross-linking (30 mW/cm2 pulsed irradiance with a total fluence ranging from 5.4 to 15 J/cm2, in concentric circles centered on the posterior float maximum). The following parameters were analyzed at the preoperative, 1-month, 6-month, and 1-year postoperative visits: corrected spectacle distance visual acuity, manifest refraction including sphere, cylinder and mean refractive spherical equivalent, corneal tomography, higher order aberration profile, and endothelial cell count. Anterior segment optical coherence tomography evaluation was performed at the 1-month postoperative visit to assess the depth of the demarcation line.

Results:
Sixty-four eyes of 45 patients (32 eyes in each group) were included. There was a significant reduction in maximum keratometry and IS asymmetry in the PiXL group at both the 6-month and 1-year postoperative visits (P = 0.001 and 0.06). Corrected spectacle distance visual acuity improved significantly in the PiXL (0.05 ± 0.08 logarithm of the minimum angle of resolution, P = 0.02) versus the standard CXL (0.01 ± 0.025 logarithm of the minimum angle of resolution, P = 0.26) group. A greater depth of a stromal demarcation line was observed in the customized CXL group (P = 0.02). No significant complications were noted in either cohort.

Conclusions:
PiXL demonstrated similar safety with significantly greater keratometry flattening and corneal regularization vis-à-vis standard CXL. This resulted in significant improvement of spectacle corrected visual acuity for eyes with mild-to-moderate keratoconus.