bluuebunny/crossref_metadata_2025_split huggingface dataset:
Avelumab Plus Axitinib as First-Line Therapy for Advanced Renal Cell Carcinoma: Long-Term Results from the JAVELIN Renal 100 Phase Ib Trial
Authors: Larkin James , Oya Mototsugu , Martignoni Marcella , Thistlethwaite Fiona , Nathan Paul , Ornstein Moshe C , Powles Thomas , Beckermann Kathryn E , Balar Arjun V , McDermott David , Gupta Sumati , Philips George K , Gordon Michael S , Uemura Hirotsugu , Tomita Yoshihiko , Wang Jing , Michelon Elisabete , di Pietro Alessandra , Choueiri Toni K 
Published: December 2022

AbstractBackgroundProgression-free survival was significantly longer in patients who received avelumab plus axitinib versus sunitinib as first-line treatment for advanced renal cell carcinoma (aRCC) in a randomized phase III trial. We report long-term safety and efficacy of avelumab plus axitinib as first-line treatment for patients with aRCC from the JAVELIN Renal 100 phase Ib trial (NCT02493751).Materials and MethodsIn this open-label, multicenter, phase Ib study, patients with untreated aRCC received avelumab 10 mg/kg every 2 weeks plus axitinib 5 mg twice daily or with axitinib for 7 days followed by avelumab plus axitinib. Safety and efficacy were assessed in all patients receiving at least one dose of avelumab or axitinib.ResultsOverall, 55 patients were enrolled and treated. Median follow-up was 55.7 months (95% CI, 54.5-58.7). Treatment-related adverse events of any grade or grade ≥3 occurred in 54 (98.2%) and 34 (61.8%) patients, respectively. The confirmed objective response rate was 60.0% (95% CI, 45.9-73.0), including complete response in 10.9% of patients. Median duration of response was 35.9 months (95% CI, 12.7-52.9); the probability of response was 65.8% (95% CI, 46.7-79.4) at 2 years. Median progression-free survival was 8.3 months (95% CI, 5.3-32.0). Median overall survival was not reached (95% CI, 40.8-not estimable); the 5-year overall survival rate was 57.3% (95% CI, 41.2-70.5).ConclusionFive-year follow-up for combination treatment with avelumab plus axitinib in previously untreated patients with aRCC showed long-term clinical activity with no new safety signals, supporting use of this regimen within its approved indication in clinical practice (Clinicaltrials.gov NCT02493751).
A sorghum ascorbate peroxidase with four binding sites has activity against ascorbate and phenylpropanoids
Authors: Zhang Bixia , Lewis Jacob A , Vermerris Wilfred , Sattler Scott E , Kang ChulHee 
Published: December 2022

AbstractIn planta, H2O2 is produced as a by-product of enzymatic reactions and during defense responses. Ascorbate peroxidase (APX) is a key enzyme involved in scavenging cytotoxic H2O2. Here, we report the crystal structure of cytosolic APX from sorghum (Sorghum bicolor) (Sobic.001G410200). While the overall structure of SbAPX was similar to that of other APXs, SbAPX uniquely displayed four bound ascorbates rather than one. In addition to the ɣ-heme pocket identified in other APXs, ascorbates were bound at the δ-meso and two solvent-exposed pockets. Consistent with the presence of multiple binding sites, our results indicated that the H2O2-dependent oxidation of ascorbate displayed positive cooperativity. Bound ascorbate at two surface sites established an intricate proton network with ascorbate at the ɣ-heme edge and δ-meso sites. Based on crystal structures, steady-state kinetics, and site-directed mutagenesis results, both ascorbate molecules at the ɣ-heme edge and the one at the surface are expected to participate in the oxidation reaction. We provide evidence that the H2O2-dependent oxidation of ascorbate by APX produces a C2-hydrated bicyclic hemiketal form of dehydroascorbic acid at the ɣ-heme edge, indicating two successive electron transfers from a single-bound ascorbate. In addition, the δ-meso site was shared with several organic compounds, including p-coumaric acid and other phenylpropanoids, for the potential radicalization reaction. Site-directed mutagenesis of the critical residue at the ɣ-heme edge (R172A) only partially reduced polymerization activity. Thus, APX removes stress-generated H2O2 with ascorbates, and also uses this same H2O2 to potentially fortify cell walls via oxidative polymerization of phenylpropanoids in response to stress.
Multibiomarker disease activity score: an objective tool for monitoring rheumatoid arthritis? A systematic review and meta-analysis
Authors: Meznerics Fanni A , Kemény Lajos V , Gunther Emese , Bakó Eszter , Dembrovszky Fanni , Szabó Bence , Ascsillán Anna , Lutz Elmar , Csupor Dezsö , Hegyi Péter , Bánvölgyi András , Nagy György 
Published: December 2022

Abstract

Objectives
The multibiomarker disease activity (MBDA) score is an objective tool for monitoring disease activity in RA. Here we report a systematic review and meta-analysis of the clinical value of the MBDA score in RA.

Methods
We performed a systematic literature search in five medical databases—MEDLINE (via PubMed), Cochrane Library (CENTRAL), Embase, Scopus and Web of Science—from inception to 13 October 2021. Original articles reporting on the performance of the MBDA score’s correlation with conventional disease activity measures or the predictive and discriminative values of the MBDA score for radiographic progression, therapy response, remission and relapse were included.

Results
Our systematic search provided a total of 1190 records. After selection and citation searches, we identified 32 eligible studies. We recorded moderate correlations between MBDA score and conventional disease activity measures at baseline [correlation (COR) 0.45 (CI 0.28, 0.59), I2 = 71.0% for the 28-joint DAS with CRP (DAS28-CRP) and COR 0.55 (CI 0.19, 0.78), I2 = 0.0% for DAS28 with ESR] and at follow-up [COR 0.44 (CI 0.28, 0.57, I2 = 70.0% for DAS28-CRP) and found that the odds of radiographic progression were significantly higher for patients with a high baseline MBDA score (&gt;44) than for patients with a low baseline MBDA score (&lt;30) [OR 1.03 (CI 1.02–1.05), I2 = 10.0%].

Conclusion
The MBDA score might be used as an objective disease activity marker. In addition, it is also a reliable prognostic marker of radiographic progression.
Modeling Diagnostic Expertise in Cases of Irreducible Uncertainty: The Decision-Aligned Response Model
Authors: Pusic Martin V. , Cook David A. , Friedman Julie L. , Lorin Jeffrey D. , Rosenzweig Barry P. , Tong Calvin K.W. , Smith Silas , Lineberry Matthew , Hatala Rose 
Published: December 2022

Purpose
Assessing expertise using psychometric models usually yields a measure of ability that is difficult to generalize to the complexity of diagnoses in clinical practice. However, using an item response modeling framework, it is possible to create a decision-aligned response model that captures a clinician’s decision-making behavior on a continuous scale that fully represents competing diagnostic possibilities. In this proof-of-concept study, the authors demonstrate the necessary statistical conceptualization of this model using a specific electrocardiogram (ECG) example.

Method
The authors collected a range of ECGs with elevated ST segments due to either ST-elevation myocardial infarction (STEMI) or pericarditis. Based on pilot data, 20 ECGs were chosen to represent a continuum from “definitely STEMI” to “definitely pericarditis,” including intermediate cases in which the diagnosis was intentionally unclear. Emergency medicine and cardiology physicians rated these ECGs on a 5-point scale (“definitely STEMI” to “definitely pericarditis”). The authors analyzed these ratings using a graded response model showing the degree to which each participant could separate the ECGs along the diagnostic continuum. The authors compared these metrics with the discharge diagnoses noted on chart review.

Results
Thirty-seven participants rated the ECGs. As desired, the ECGs represented a range of phenotypes, including cases where participants were uncertain in their diagnosis. The response model showed that participants varied both in their propensity to diagnose one condition over another and in where they placed the thresholds between the 5 diagnostic categories. The most capable participants were able to meaningfully use all categories, with precise thresholds between categories.

Conclusions
The authors present a decision-aligned response model that demonstrates the confusability of a particular ECG and the skill with which a clinician can distinguish 2 diagnoses along a continuum of confusability. These results have broad implications for testing and for learning to manage uncertainty in diagnosis.
Impact of Students’ Scheduling Choice on Clerkship Examination Score Performance in a Time-Varying Competency-Based Curriculum
Authors: Kraakevik Jeff A. , Haedinger Leslie A. , Guzman Cirila Estela Vasquez , Kahl Leslie , Smeraglio Anne , Bonura Erin , Hasan Reem , Paquin Ashley , Moulton Bart , Carney Patricia A. 
Published: December 2022

Purpose
Standardized end-of-clerkship examinations typically occur on the last day of the clerkship. However, recent trends toward time-varying competency-based medical education have offered students more test scheduling flexibility, creating an opportunity to study the impact of student-selected examination timing.

Method
Starting with the graduating class of 2018, students took the required standardized end-of-core clerkship examinations at any available time they chose during their clinical years. Before this change, these examinations were administered to all students on the last day of the clerkship. Students’ examination dates relative to clerkship completion were analyzed between 2017 and 2020 (inclusive of before and after flexible exam timing) to assess the impact that student-selected exam timing had on test performance on National Board of Medical Examiners shelf clinical science examinations for required core clerkships.

Results
Data on 146 medical students in 2017 (fixed exam timing) and 466 medical students between 2018 and 2020 (flexible exam timing) were included. Among students offered flexible exam timing, between 2.7% (internal medicine) and 14.6% (psychiatry) took their exam before actually taking clerkship, while between 22.7% (psychiatry) and 40.0% (surgery) took their exam more than 90 days after the clerkship ended. Exam scores were statistically higher for those who took the exam at a time of their choosing compared with those who were required to take it at the end of individual rotations and when the exam scores were combined (fixed exam timing mean = 73.9, standard deviation [SD] = 7.8; flexible exam timing mean = 77.4, SD = 6.0, P < .001). The percent of students with passing scores was statistically higher in internal medicine, pediatrics, and psychiatry.

Conclusions
Self-selection of shelf exam timing appears to increase shelf exam scores. As more medical schools transition to competency-based medical education, providing scheduling flexibility appears not to negatively affect student achievement.
Promotion of a Mastery Orientation to Learning in Medical School: Implementation of the Not Yet Pass Grade
Authors: Colbert-Getz Jorie M. , Lindsley Janet , Moore Kathryn B. , Formosa Tim , Pippitt Karly 
Published: December 2022

Problem
Using pass/fail (P/F) course grades may motivate students to perform well enough to earn a passing grade, giving them a false sense of competence and not motivating them to remediate deficiencies. The authors explored whether adding a not yet pass (NYP) grade to a P/F scale would promote students’ mastery orientation toward learning.

Approach
The authors captured student outcomes and data on time and cost of implementing the NYP grade in 2021 at the University of Utah School of Medicine. One cohort of medical students, who had experienced both P/F and P/NYP/F scales in years 1 and 2, completed an adapted Achievement Goal Questionnaire–Revised (AGQ-R) in fall 2021 to measure how well the P/NYP/F grading scale compared with the P/F scale promoted mastery orientation and performance orientation goals. Students who received an NYP grade provided feedback on the NYP process.

Outcomes
Students reported that the P/NYP/F scale increased their achievement of both mastery and performance orientation goals, with significantly higher ratings for mastery orientation goals than for performance orientation goals on the AGQ-R (response rate = 124/125 [99%], P ≤ .001, effect size = 0.31). Thirty-eight students received 48 NYP grades in 7 courses during 2021, and 3 (2%) failed a subsequent course after receiving an NYP grade. Most NYP students reported the NYP process enabled them to identify and correct a deficiency (32/36 [89%]) and made them feel supported (28/36 [78%]). The process was time intensive (897 hours total for 48 NYP grades), but no extra funding was budgeted.

Next Steps
The findings suggest mastery orientation can be increased with an NYP grade. Implementing a P/NYP/F grading scale for years 1 and/or 2 may help students transition to programmatic assessment or no grading later in medical school, which may better prepare graduates for lifelong learning.
Risk factors for local recurrence of giant cell tumor of bone of the extremities: a retrospective study
Authors: AbdelKawi Noureldin Mohamed , Abed Yasser Youssef , El-negery Abed Abdelatif , Kotb Samir Zaki Mohamed 
Published: December 2022

Background:
Although considered as a benign tumor, giant cell tumor of bone (GCTB) has an aggressive biological behavior with high tendency for local recurrence (LR). The most commonly used method of treatment of GCTB is intralesional curettage augmented by various types of local adjuvants. The aim of this study was to evaluate the rate of recurrence of GCTB after surgical treatment to detect the risk factors that may influence the rate of LR.

Methods:
Fifty-two cases of GCTB that had been treated in a university hospital musculoskeletal oncology unit, between 2012 and 2017 were retrospectively reviewed after minimal follow-up of 4 yr and risk factors of LR were determined.

Results:
All LRs occurred within the first 3 yr (4 to 31 mo). Curettage was used to manage 34 patient cases, from which 11 patients (32.4%) showed LR. Only one patient (5.6%) of the 18 wide local excision patients developed recurrence. The highest recurrence rate was found among the lesions of the proximal femur. Neither the tumor volume nor the pathological grade had a significant impact on the rate of LR. The presence of soft-tissue invasion, occurrence of pathological fracture at presentation and using curettage as a method of treatment were associated with significantly higher rate of LR.

Conclusions:
Lesions in the proximal femur, occurrence of pathological fracture at presentation, soft-tissue invasion, and curettage as management option were found to be associated with an increased risk of LR of GCTB.

Level of Evidence:
Level III
Antibiotic prophylaxis for dental procedures after joint arthroplasty: a cross-sectional survey of orthopaedic surgeons about current practices
Authors: Del Prince Clayton , Pavlesen Sonja , DiPaola Matthew J. 
Published: December 2022

Background:
Periprosthetic joint infection is a rare, but potentially devastating complication that can occur after prosthetic joint replacement. In 2016, the American Academy of Orthopaedic Surgeons (AAOS) revised its Appropriate Use Criteria (AUC) for the Management of Patients with Orthopaedic Implants Undergoing Dental Procedures. The objective of this study was to survey orthopaedic surgeons regarding their use of prophylactic antibiotics in arthroplasty patients undergoing dental procedures. Additionally, the authors inquired whether surgeons who have undergone arthroplasty procedures themselves practice the antibiotic prophylaxis when faced with decisions regarding their own joints.

Methods:
The authors surveyed currently practicing orthopaedic surgeons in the United States who perform joint arthroplasty procedures. The questions pertained to demographic data, training background, type of employment, arthroplasty type and volume, antibiotic prophylaxis practices, and awareness of the AAOS/American Dental Association (ADA) recommendations.

Results:
Two hundred, fourteen surveys were completed, though not all respondents answered every question. Most surgeons (149 of 200, 74.5%) routinely recommend prophylactic antibiotics for all patients with total joint arthroplasties who undergo dental procedures. The majority of the surgeons (163 of 199, 81.9%) reported that they are aware of the current AAOS/ADA guidelines, but that did not have a substantial effect on whether they routinely recommend prophylactic antibiotics (P=0.74).

Conclusions:
Most orthopaedic surgeons surveyed said they understand the AAOS/ADA guidelines, but that they routinely prescribe prophylactic antibiotics for arthroplasty patients undergoing dental procedures. These prescribing practices have no significant relationship with their knowledge of the AAOS AUC, years of experience, volume, specialty, employment, or personal history of joint replacement.

Level of Evidence:
Level IV, cross-sectional survey
Discordance in current procedural terminology coding for pediatric orthopaedic surgeries between residents and attending surgeons: a retrospective comparative study
Authors: Wolf G. Jacob , O’Leary Ryan J. , Tranchitella Nicholas M. , Johnson Charles A. , Van Nortwick Sara S. , Dow Matthew A. , Murphy Robert F. 
Published: December 2022

Background:
The current procedural terminology (CPT) coding system is used in medical record maintenance and billing. CPT coding is a skill that residents should acquire through training. The purpose of this study was to assess concordance between attending and resident coding practices in pediatric orthopaedic surgery.

Methods:
Case log reports were collected from 14 residents on the pediatric orthopaedic surgery service over 2 yr, then compared to operating room billing records from three pediatric orthopaedic surgeons. CPT code concordance rates were generated between residents and attendings for individual cases.

Results:
Three attending surgeons performed 1,372 cases over the two years. To accommodate cases in which multiple residents participated, 38 cases were duplicated (1,410 total attending cases). There was no corresponding resident case entry for 31.3% of attending cases. Of the 968 cases logged by residents, a 78.2% concordance rate was observed. Residents who rotated on pediatric orthopaedics only as a post-graduate year (PGY) 3 during the study period exhibited 73.8% concordance rates, versus residents that rotated as both a PGY-3 and PGY-4 who exhibited 78.7% and those who rotated only as a PGY-4 who exhibited 82.0% (P<0.001). Closed reduction and percutaneous pinning of supracondylar humerus fractures had the highest concordance rate (93.5%) among ACGME-required minimum category cases.

Conclusions:
Residents and attendings demonstrate a relatively high CPT code concordance among pediatric orthopaedic surgeries. Concordance rates were significantly higher when reported by more experienced residents. Among minimum category cases, percutaneous pinning of supracondylar humeral fractures demonstrated the highest concordance rate.

Level of Evidence:
Level IV
Assessment of risk-stratified approach to thromboprophylaxis in hip arthroplasty patients: a prospective cohort study
Authors: Bhaskarwar Ajit P. , Kumar Narinder 
Published: December 2022

Background:
Venous thromboembolism (VTE) is a frequent and serious complication in orthopaedic surgeries of the lower limbs. Subsequent pulmonary embolism (PE) makes it the most common cause of death after joint replacement surgeries of the lower limbs. In this study, a multimodal approach for thromboprophylaxis was adopted in patients undergoing total hip replacement (THR) and hemiarthroplasty (HA), including pharmaceutical and mechanical agents recommended by the American Academy of Orthopaedic Surgeons (AAOS) as per risk stratified approach, and the effectiveness of the same was measured by clinical and radiographic assessment.

Methods:
This was a prospective observational longitudinal study with evaluation at multiple points of time carried out at a tertiary care orthopaedic center. The study included 66 consecutive patients who underwent hip replacement arthroplasty (45 THR, 21 HA). Mechanical and pharmacological (soluble aspirin) prophylaxis modalities for deep venous thrombosis (DVT) were administered to all patients after risk stratification. Patients were assessed for evidence of DVT at 2,6, and 12 wk postoperatively by clinical tests and color Doppler flow imaging (CDFI).

Results:
This study confirmed efficacy of AAOS recommended risk stratified approach of thromboprophylaxis by combined use of soluble aspirin and various other mechanical measures in patients having standard risk for PE and bleeding undergoing THR or HA because none of the patients developed DVT per clinical assessment and confirmed by CDFI carried out at follow-up.

Conclusions:
Prevention of DVT as recommended by AAOS has proven to be effective as well as cheaper in moderate-risk patients undergoing hip replacement surgery. Though there were no major differences in complication rates in respect to other prophylaxis except prevalence of major bleeding was very low.

Level of Evidence:
Level II
Incidence and risk factors of ankle fusion after pilon fracture: a retrospective review
Authors: Massey Lauren E. , Oladeji Lasun O. , Esposito Ennio Rizzo , Cook James L. , Della Rocca Gregory J. , Crist Brett D. 
Published: December 2022

Background:
Pilon fractures are associated with a high incidence of complications, yet there continues to be uncertainty regarding variables associated with adverse outcomes after pilon open reduction and internal fixation (ORIF). This study sought to characterize the rate of arthrodesis and identify risk factors that increase the likelihood of ankle arthrodesis in patients with ORIF pilon fractures.

Methods:
After institutional review board approval, a retrospective review was conducted to identify patients who underwent ORIF of pilon fractures at an ACS Level I trauma center from 2005 to 2014. Medical records and radiographs were reviewed retrospectively for patient demographics, comorbidities, fracture characteristics, associated injuries, mechanism of injury, and functional activity. Logistic regression analyses were performed to identify risk factors associated with arthrodesis.

Results:
282 pilon fractures (279 patients) met inclusion criteria. There were 182 men and 97 women with an average age of 43.8±15.2 yr. Overall, 15 pilon fractures (5.3%) in six male patients and nine female patients were treated with an ankle arthrodesis an average of 1.73±5.15 yr after their initial injury. Following multivariable logistic regression analysis, age greater than 40 yr, tobacco use, and nonunion were identified as independent predictors of arthrodesis.

Conclusions:
This study found a number of patient-related factors associated with an increased risk of arthrodesis after a pilon fracture was sustained. Multivariable logistical analysis identified age greater than 40 yr, tobacco use, and nonunion as independent predictors of arthrodesis following pilon fracture ORIF.

Level of Evidence:
Level III
The safety of intraarticular injection prior to total hip arthroplasty: a review
Authors: Chan Peter Y.W. , Huo Michael H. 
Published: December 2022

Osteoarthritis is a chronic and debilitating condition, and the hip joint is commonly affected. Total hip arthroplasty is an effective treatment for end-stage osteoarthritis. Intraarticular injections may be used to treat pain relief before total hip arthroplasty. There are controversies on whether intraarticular injections prior to total hip arthroplasty are safe because of concerns that they may increase the risk of infection after surgery. This study reviewed the most current published evidence from the past 20 yr regarding the risks of infection from intraarticular injections before total hip arthroplasty.