bluuebunny/crossref_metadata_2025_split huggingface dataset:
Primary nasal Kaposi Sarcoma in well-controlled HIV-positive patient with normal CD4 count associated with long-term nasal steroid use
Authors: Htet Kyaw Zin , Waul Michael , Edelstein Howard , Mui Stanley , Cherny Sarah , Leslie Kieron 
Published: February 2021

Kaposi sarcoma (KS) is an angioproliferative disease that is caused by human herpesvirus 8. The epidemic form of KS is associated with acquired immunodeficiency syndrome (AIDS) and is common in HIV-positive patients with CD4 counts less than 200 cells/mm. We present the case of a 63-year-old man with well-controlled HIV and normal CD4 count developing atypical nasal KS associated with intranasal steroid use.
The impact of major trauma centre designation on routine orthopaedic trauma care
Authors: Archer James , Odeh Abdulrahman , Piper Danielle , Moore Ellen , Butt Annisa , Fawdington Ross , Fenton Paul 
Published: February 2021

Introduction Major Trauma networks were introduced in 2012 to improve care for patients with major traumatic injuries. Current evidence suggests that this has been successfully achieved, however, there are implications for ‘routine trauma care’ of patients who attend a major trauma centre. Methods We assessed time from injury to surgery in August to October in 2011 and 2019. We also assessed the National Hip Fracture Database outcomes for time to surgery for hip fracture patients. Results Average wait times for ankle surgery increased from 4.9 days (18 patients) in 2011 to 7.0 in days (26 patients) in 2019, whilst for distal radius fracture surgery increased from 3.9 days (36 patients) to 6.5 days (23 patients); the percentage of patients who received their hip fracture surgery within the recommended 36 hours was 53.7% in 2011 (322 patients) compared to 66.7% in 2019 (375 patients). Conclusion The wait times for ‘routine trauma care’ have increased since the introduction of the major trauma network. This is probably due to the large demand on major trauma centres presented by complex trauma patients. However, the number of patients undergoing hip fracture surgery within 36 hours has improved, probably driven by the NHS tariff for hip fracture care. Changes to the current major trauma system or an increase in resources are required to help reverse this trend.
Injury Prevention Programs for Throwing Injuries in Softball Players: A Systematic Review
Authors: Paul Jonathan , Brown Symone M. , Mulcahey Mary K. 
Published: February 2021

Context: Throwing-related injuries occur commonly in softball players. Preventative programs can be implemented to assist in identifying and correcting risk factors that could potentially lead to injury and therefore time missed from both practice and games. Objective: The purpose of this study was to determine if position-specific injury prevention programs have been developed to decrease the risk of throwing-related injuries in softball players. Data Sources: A systematic review was performed using the PRISMA (Preferred Reporting Items of Systematic Reviews and Meta-Analyses) guidelines. PubMed, PMC, and EBSCO were searched for articles on injury prevention programs using the following key terms: softball, injury prevention, throwing injuries, pitcher, and shoulder. Study Selection: Studies that involved fast-pitch softball and included female participants as well as rehabilitation programs were included. Articles that highlighted slow-pitch softball or did not include female participants were excluded. Level of Evidence: Level 1. Data Extraction: The initial search identified 1605 articles. After implementing a filter, 131 articles remained. Thirteen articles were screened out as duplicates. After screening for inclusion criteria, 7 articles remained and were included in the systematic review. Results: Decreased range of motion (ROM) in both the upper and the lower extremities, unbalanced muscular strength, and fatigue were identified as risk factors for throwing injuries in softball players. Within the upper extremity, strength and ROM of the rotator cuff muscles, biceps, and extensors of the forearm were emphasized. The main focus of the lower extremity was the strength of the gluteal muscles and ROM of the lumbopelvic-hip complex. Only 1 study detailed an injury prevention program for softball players. The prevention program outlined was generalized for all softball players and was not position specific. Conclusion: There is a paucity of information about injury prevention programs for softball players. Of the evidence analyzed, balanced strengthening of the upper and lower extremities while maintaining dynamic range of motion was frequently utilized in developing an injury prevention program.
COVID-19: The Oral and Maxillofacial Surgery Experience, Oxford, UK
Authors: Visholm Toby M. , Sandhu Neha , Dhariwal Daljit K. 
Published: February 2021

Study Design: In response to the COVID-19 pandemic the Oxford Oral and Maxillofacial Surgery Department, that operates as a Hub and Spoke model underwent several changes to its structure to respond to the change in service. This study is an audit of all emergency patients seen during a 10-week period and compared these patients to the same time period 1-year previous. Objective: The objective was to observe the change in the service provision during the COVID-19 pandemic. Methods: This study prospectively recorded all the emergency referrals, inpatient admissions and emergency outpatient reviews during a 10-week period, this was compared to data from the same time period in 2019. Results: The unit saw a statistically significant decrease in the number of facial lacerations (p = 0.0007) and fractured mandibles (p = 0.0067) and received a statistically significant increase in patients presenting with dental abscesses (p = 0.0067). Average length of inpatient stay was reduced from 2.4 days to 1.7; of these patients significantly less were reviewed face to face (p = 0.026) in favor of telemedicine options. Conclusions: During this period, the hub and spoke model allowed the service to quickly adapt during the COVID pandemic aiding the dissemination of new guidelines and establishing hub and spoke local consultant led daily emergency and follow up clinics. The Specialist Training Registrars were located in the central hub which allowed the service to have 24-hour resident senior decision makers and enabled the redeployment of junior doctors. The authors believe that the Hub and Spoke model allowed their workforce and resources to best serve their patient population.
Notes from the Field: Results from the Parent Acceptance of Pediatric Integrated Care Survey
Authors: Bruni Teryn , Birnbaum Richard , Turnier Luke , Caserta Abigail , Maragakis Alexandros , Tennant Katherine , Lancaster Blake 
Published: February 2021

Objective: To collect data and gain an understanding of parental satisfaction with and attitudes toward treatment in a pediatric integrated primary care (IPC) model. Data Sources: Primary data were collected across the United States over the course of a few months. Study Design: The 35-item, Parent Acceptance of Pediatric Integrated Care Survey (PAPICS) was developed by a panel of IPC experts. The survey was then distributed through the Qualtrics Panels Service with recruited participants (i.e., parents with children under 18-years-old) receiving a $4.00 incentive for their involvement. Data Collection/Extraction Methods: A single exploratory factor analysis was performed along with four factor retention tests and clinical judgment to guide factor selection. A 5-factor structure was selected. Principal Findings: Parents reported a high level of comfort with an IPC model and a favorable attitude toward child therapy, with some concerns regarding psychological stigma and privacy. Notable variation in parents’ beliefs regarding one-on-one psychological service delivery were observed. Conclusions: Results provided evidence for parental openness to an IPC model. Findings also highlighted potential fundamental misunderstandings regarding evidence-based psychological treatment methods for children and adolescents.
Motukoreaite, a new hydrated carbonate, sulphate, and hydroxide of Mg and Al from Auckland, New Zealand
Authors: Rodgers K. A. , Chisholm J. E. , Davis R. J. , Nelson C. S. 
Published: February 2021

Motukoreaite occurs as relatively abundant, white, clay-like cement in both beach-rock and basaltic volcanic tuffs on the flanks of a small, extinct, late Pleistocene, basaltic cone at Brown's Island (Motukorea), within Waitemata Harbour, Auckland, New Zealand (36° 50′ S., 174° 35′ E.). The occurrence was originally recorded by Bartrum (1941) as ‘beach limestone’ found at two places of the island's shore. The beach-rock consists of a grain-supported fabric of poorly sorted, well-rounded, alkali-olivine basalt pebbles and granules, subangular to sub-rounded fresh olivine sand and abraded sand- and gravel-sized bioclasts in a colourless to pale yellow-green aphanocrystalline matrix of motukoreaite. Additional detritals include quartz, feldspar, and sedimentary rock fragments. Stereoscan examination of the surface of pieces of the cement prised from the beach-rock showed a box-work of plate-like crystals with a hexagonal form in which individuals measured about 3×3×0·02 microns (fig. 1).Wet-chemical analysis of a separate of the cement containing some 5 % quartz and traces of calcite and goethite gives SiO2 5·55, Al2O3 17·87, Fe2O3 0·73, CaO 0·92, MgO 22·98, MnO 0·70, ZnO 0·56, Na2O 0·71, K2O 0·10, CO2 9·32, SO3 10·00, H2O+ 19·62, H2O- 10·35, sum 99·41 %. The unit-cell formula using obtained unit-cell constants and measured specific gravity 1·43) is (Na0·73K0·07)∑0·80(Mg18·13Mn0·32Zn0·21)∑18·66Al11·15(CO3)6·22(SO4)3·97 (OH)51·1927·20H2O. Of several idealized formulae that may be proposed NaMg19Al12(CO3)6.5 (SO4)4(OH)54·28H2O is preferred.
From Fatigue Surveys to Survey Fatigue - Notes from Daily Hematology Practice
Authors: Matzdorff Axel , Rüffer Jens U. , Meyer Oliver 
Published: February 2021

Background: Monitoring fever, pain, and nausea has become a daily routine in hematology and oncology practice. Fatigue is also common but thematized much less often. Therefore, guidelines and professional organizations recommend implementing fatigue assessment in daily oncology practice. The current deficits can be explained by diverging scientific concepts, inconsistent definitions, and lack of consensus on measurement and therapy. As a quality improvement initiative and first step towards better fatigue assessment we wanted to find out which fatigue questionnaire is best suited for our patients.
Methods: On two educational meetings on general oncology issues we invited patients and healthy controls to participate in an anonymous survey. We distributed three different fatigue questionnaires (Fatigue Assessment Scale - FAS, Functional Assessment of Cancer Therapy-Fatigue-Scale - FACT-F, EORTC questionnaire on cancer related fatigue - EORTC QLQ-FA12, one for each participant) and asked to rate the questionnaires on a 5-point scale (1= fitting best to 5 = not fitting). We also counted the number of questions that had been left blank.
Results: Seventy-seven of 90 questionnaires were returned (85%). The average approval rating of the FAS questionnaire was 2.3 (patients n=10, score 2.0; controls n=35, score 2.3), of EORTC QLQ-FA12 2.4 (patients n=8, score 2.4; controls n=8, score 2.4), and of FACT-F 2.1 (patients n=9, score 2.0; controls n=7, score 2.3). The percentage of questions that had been left blank with FAS was 0.5%, 3% with EORTC QLQ-FA12, and 14% with FACT-F.
Conclusion: This survey did not measure fatigue and we do not know how many of our patients had fatigue. Its purpose was to assess the acceptance of three different fatigue questionnaires. The unexpected finding was that the average rating of all three questionnaires was remarkably similar and close to neutral. The number of blanks was highest with the EORTC QLQ-FA12 questionnaire which had more items than the two others. One explanation could be, that participants do not value questionnaires when they are long ("survey fatigue"). Maybe participants perceive fatigue as a personal failure and do not want to reveal this on a questionnaire, particularly not when there is a chance that this goes into their patient file. Questionnaires were developed for scientific research but might not be the right instrument to thematize fatigue in the setting of a busy hemato-oncology practice.

Disclosures
Matzdorff: Novartis Oncology: Consultancy, Other: Honoraria paid to institution; Amgen GmbH: Consultancy, Other: Honoraria paid to institution; Grifols Deutschland GmbH: Consultancy, Other: Honoraria paid to institution; Swedish Orphan Biovitrium GmbH: Consultancy, Other: Honoraria paid to institution; UCB Biopharma SRL: Consultancy, Other: Honoraria paid to institution; Roche Pharma AG: Other: Family stockownership. Meyer:Grifols Germany: Consultancy, Honoraria; Amgen GmbH: Honoraria; Novartis Pharma GmbH: Honoraria.
Real-World Outcomes of Patients Treated with Single-Agent Ibrutinib for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL): A Systematic Review and Meta-Analysis
Authors: Cheung Matthew C. , Amitai Irina 
Published: February 2021

BACKGROUND: Ibrutinib improves progression-free survival (PFS) compared to chemo-immunotherapy in both previously untreated and relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL; hereafter, CLL) patients. Adverse events, such as atrial fibrillation, bleeding and fungal infections, are the leading cause of drug discontinuation. Observational studies of real-world patients suggest that the rate of ibrutinib-related adverse events is higher in practice than in clinical trials. Dose reductions and drug discontinuations are more common, which may affect outcomes, although evidence has been conflicting.
OBJECTIVES: The objective of this study is to systematically review and synthesize real-world toxicity and tolerability of CLL patients on ibrutinib.
METHODS: Prospective and retrospective cohort studies and case series of patients with CLL treated with single agent ibrutinib as first or subsequent line treatment outside of clinical trials were retrieved from the Pubmed, Embase, and CENTRAL databases. Studies were critically appraised using Joanna-Briggs Institute checklists. Meta-analyses of studies deemed of moderate to high quality were done if the risk of heterogeneity was low.
RESULTS: We screened 4458 titles and abstracts and moved 251 records to full-text review. 25 full-text studies were included in the qualitative analysis. Most studies were of low to moderate quality. Rates of any bleeding ranged from 5.4 to 54.1 events/100 persons-year. Rates of severe bleeding ranged from 0 to 6.4 events/100 persons-year. Rate of infection was 9.2 to 49.8 infections/100 persons-year. Rate of atrial fibrillation varied from 2.5 to 26.0 events/100 persons-year. Pooled estimate of risk of atrial fibrillation per 100 person-years was 7.0 (95% CI 5.8, 8.2) by meta-analysis of moderate quality studies. Rate of dose reductions varied from 15.1 to 26.8 events/100 person-years, and dose reductions did not affect outcomes. The rate of drug discontinuation varied from 6.4 to 55.2 events/100 person-years. The most common cause for drug discontinuation was adverse events.
CONCLUSION: The risk of atrial fibrillation is higher in the real-world than reported from clinical trials. There was a large range of prevalence of other bleeding and infection. These adverse events were the leading cause of dose reduction and drug discontinuation. This study has many limitations arising from heterogeneity of patient characteristics and outcomes ascertainment. This highlights the need for standardized post-marketing studies of new drugs and for inclusive criteria for inclusion into randomized controlled trials.

Disclosures
No relevant conflicts of interest to declare.
Examination of Real-World Outcomes and Health Care Resource Utilization in the Prevention and Treatment of Tumor Lysis Syndrome
Authors: Balcerski Wynter , Chatterjee Kaustav , Barnes Yvonne J , Drea Ed 
Published: February 2021

BACKGROUND AND OBJECTIVE: Tumor lysis syndrome (TLS), a potentially fatal oncologic complication, can have a significant clinical and economic impact to patients and the healthcare system. The aim of this poster is to examine real world healthcare resource utilization assessments in patients treated with rasburicase for the prevention or management of tumor lysis hyperuricemia.
METHODS: Four separate oncology E.H.R. database recent publications were selected for assessment of the prevention and treatment of hyperuricemia associated with TLS. The separate databases include data from 400 hospitals across 42 states, 14,383 newly-diagnosed lymphoma patients across 101 hospitals in a non-profit community oncology network, 21 healthcare organizations accounting for a total of 26 million patients, and 750,000 community oncology patients that includes 25,000 active OCM practices. The separate studies queried databases for patients at high risk of hyperuricemia of TLS inclusive of tumor diagnosis, uric acid, LDH, WBC, uricosuric agent, site of care, and health resource utilization such as hospitalization and length of stay.
RESULTS:
See Table
CONCLUSIONS: Across the findings from 4 separate retrospective, real-world studies assessing the prevention and management of hyperuricemia of TLS, the application of criteria for the identification of patients at intermediate or high risk are not universally applied. Recognition of clinical risk factors for hyperuricemia of TLS are needed for the timely and appropriate selection of therapy to prevent hyperuricemia of chemotherapy.
Table

Disclosures
Balcerski: Sanofi Genzyme: Current Employment. Chatterjee:Sanofi: Current Employment. Barnes:Sanofi: Current Employment. Drea:Sanofi/Genzyme: Current Employment.
Defective palmitoylation of transferrin receptor triggers iron overload in Friedreich ataxia fibroblasts
Authors: Petit Floriane , Drecourt Anthony , Dussiot Michaël , Zangarelli Coralie , Hermine Olivier , Munnich Arnold , Rötig Agnès 
Published: February 2021

Abstract
Friedreich ataxia (FRDA) is a frequent autosomal recessive disease caused by a GAA repeat expansion in the FXN gene encoding frataxin, a mitochondrial protein involved in iron-sulfur cluster (ISC) biogenesis. Resulting frataxin deficiency affects ISC-containing proteins and causes iron to accumulate in the brain and heart of FRDA patients. Here we report on abnormal cellular iron homeostasis in FRDA fibroblasts inducing a massive iron overload in cytosol and mitochondria. We observe membrane transferrin receptor 1 (TfR1) accumulation, increased TfR1 endocytosis, and delayed Tf recycling, ascribing this to impaired TfR1 palmitoylation. Frataxin deficiency is shown to reduce coenzyme A (CoA) availability for TfR1 palmitoylation. Finally, we demonstrate that artesunate, CoA, and dichloroacetate improve TfR1 palmitoylation and decrease iron overload, paving the road for evidence-based therapeutic strategies at the actionable level of TfR1 palmitoylation in FRDA.
Targeting of canonical WNT signaling ameliorates experimental sclerodermatous chronic graft-versus-host disease
Authors: Zhang Yun , Shen Lichong , Dreißigacker Katja , Zhu Honglin , Trinh-Minh Thuong , Meng Xianyi , Tran-Manh Cuong , Dees Clara , Matei Alexandru-Emil , Chen Chih-Wei , Ditschkowski Markus , Krauss Stefan , Winkler Julia , Wolff Daniel , Ziemer Mirjana , Beilhack Andreas , Karrer Sigrid , Herr Wolfgang , Mackensen Andreas , Schett Georg , Spriewald Bernd M. , Distler Jörg H. W. 
Published: February 2021

AbstractChronic graft-versus-host disease (cGVHD) is a major life-threatening complication of allogeneic hematopoietic stem cell transplantation. The molecular mechanisms underlying cGVHD remain poorly understood, and targeted therapies for clinical use are not well established. Here, we examined the role of the canonical WNT pathway in sclerodermatous cGVHD (sclGVHD). WNT signaling was activated in human sclGVHD with increased nuclear accumulation of the transcription factor β-catenin and a WNT-biased gene expression signature in lesional skin. Treatment with the highly selective tankryase inhibitor G007-LK, the CK1α agonist pyrvinium, or the LRP6 inhibitor salinomycin abrogated the activation of WNT signaling and protected against experimental cGVHD, without a significant impact on graft-versus-leukemia effect (GVL). Treatment with G007-LK, pyrvinium, or salinomycin almost completely prevented the development of clinical and histological features in the B10.D2 (H-2d) → BALB/c (H-2d) and LP/J (H-2b) → C57BL/6 (H-2b) models of sclGVHD. Inhibition of canonical WNT signaling reduced the release of extracellular matrix from fibroblasts and reduced leukocyte influx, suggesting that WNT signaling stimulates fibrotic tissue remodeling by direct effects on fibroblasts and by indirect inflammation-dependent effects in sclGVHD. Our findings may have direct translational potential, because pyrvinium is in clinical use, and tankyrase inhibitors are in clinical trials for other indications.
Structure of blood coagulation factor VIII in complex with an anti–C1 domain pathogenic antibody inhibitor
Authors: Gish Joseph S. , Jarvis Lexi , Childers Kenneth C. , Peters Shaun C. , Garrels Connor S. , Smith Ian W. , Spencer H. Trent , Doering Christopher B. , Lollar Pete , Spiegel P. Clint 
Published: February 2021

Abstract
Antibody inhibitor development in hemophilia A represents the most significant complication resulting from factor VIII (fVIII) replacement therapy. Recent studies have demonstrated that epitopes present in the C1 domain contribute to a pathogenic inhibitor response. In this study, we report the structure of a group A anti–C1 domain inhibitor, termed 2A9, in complex with a B domain–deleted, bioengineered fVIII construct (ET3i). The 2A9 epitope forms direct contacts to the C1 domain at 3 different surface loops consisting of Lys2065-Trp2070, Arg2150-Tyr2156, and Lys2110-Trp2112. Additional contacts are observed between 2A9 and the A3 domain, including the Phe1743-Tyr1748 loop and the N-linked glycosylation at Asn1810. Most of the C1 domain loops in the 2A9 epitope also represent a putative interface between fVIII and von Willebrand factor. Lastly, the C2 domain in the ET3i:2A9 complex adopts a large, novel conformational change, translocating outward from the structure of fVIII by 20 Å. This study reports the first structure of an anti–C1 domain antibody inhibitor and the first fVIII:inhibitor complex with a therapeutically active fVIII construct. Further structural understanding of fVIII immunogenicity may result in the development of more effective and safe fVIII replacement therapies.