bluuebunny/crossref_metadata_2025_split huggingface dataset:
Towards Response ADAptive Radiotherapy for organ preservation for intermediate-risk rectal cancer (preRADAR): protocol of a phase I dose-escalation trial
Authors: Verweij Maaike E , Tanaka Max D , Kensen Chavelli M , van der Heide Uulke A , Marijnen Corrie A M , Janssen Tomas , Vijlbrief Tineke , van Grevenstein Wilhelmina M U , Moons Leon M G , Koopman Miriam , Lacle Miangela M , Braat Manon N G J A , Chalabi Myriam , Maas Monique , Huibregtse Inge L , Snaebjornsson Petur , Grotenhuis Brechtje A , Fijneman Remond , Consten Esther , Pronk Apollo , Smits Anke B , Heikens Joost T , Eijkelenkamp Hidde , Elias Sjoerd G , Verkooijen Helena M , Schoenmakers Maartje M C , Meijer Gert J , Intven Martijn , Peters Femke P 
Published: June 2023

IntroductionOrgan preservation is associated with superior functional outcome and quality of life (QoL) compared with total mesorectal excision (TME) for rectal cancer. Only 10% of patients are eligible for organ preservation following short-course radiotherapy (SCRT, 25 Gy in five fractions) and a prolonged interval (4–8 weeks) to response evaluation. The organ preservation rate could potentially be increased by dose-escalated radiotherapy. Online adaptive magnetic resonance-guided radiotherapy (MRgRT) is anticipated to reduce radiation-induced toxicity and enable radiotherapy dose escalation. This trial aims to establish the maximum tolerated dose (MTD) of dose-escalated SCRT using online adaptive MRgRT.Methods and analysisThe preRADAR is a multicentre phase I trial with a 6+3 dose-escalation design. Patients with intermediate-risk rectal cancer (cT3c-d(MRF-)N1M0 or cT1-3(MRF-)N1M0) interested in organ preservation are eligible. Patients are treated with a radiotherapy boost of 2×5 Gy (level 0), 3×5 Gy (level 1), 4×5 Gy (level 2) or 5×5 Gy (level 3) on the gross tumour volume in the week following standard SCRT using online adaptive MRgRT. The trial starts on dose level 1. The primary endpoint is the MTD based on the incidence of dose-limiting toxicity (DLT) per dose level. DLT is a composite of maximum one in nine severe radiation-induced toxicities and maximum one in three severe postoperative complications, in patients treated with TME or local excision within 26 weeks following start of treatment. Secondary endpoints include the organ preservation rate, non-DLT, oncological outcomes, patient-reported QoL and functional outcomes up to 2 years following start of treatment. Imaging and laboratory biomarkers are explored for early response prediction.Ethics and disseminationThe trial protocol has been approved by the Medical Ethics Committee of the University Medical Centre Utrecht. The primary and secondary trial results will be published in international peer-reviewed journals.Trial registration numberWHO International Clinical Trials Registry (NL8997;https://trialsearch.who.int).
Cardiotocography in practice: a qualitative study to explore obstetrical care professionals’ experiences with using cardiotocography information in Dutch practice
Authors: Romijn A , Bakker P C A M , Teunissen P W 
Published: June 2023

ObjectiveThis study aimed to explore obstetric care professionals’ experiences with using cardiotocograph (CTG) information and how they employ this tool in their practice.DesignQualitative study, involving 30 semi-structured interviews and two focus group sessions. Conventional content analysis was used for data analysis.SettingAmsterdam University Medical Centers in the Netherlands.ParticipantsIn total, 43 care professionals participated. The respondents included obstetricians, residents in obstetrics and gynaecology, junior physicians, clinical midwives and nurses.FindingsThree main categories were identified that influenced the use of cardiotocography in practice; (1) individual characteristics involving knowledge, experience and personal beliefs; (2) teams involving collaboration in and between shifts and (3) work environment involving equipment, culture and continuing development.ConclusionThis study underlines the importance of teamwork when working with cardiotocography in practice. There is a particular need to create shared responsibility among team members for cardiotocography interpretation and appropriate management, which should be addressed in educational programmes and regular multidisciplinary meetings, to allow learning from colleagues’ perspectives.
Neurodiversity in elite sport: a systematic scoping review
Authors: Hoare Erin , Reyes Jonathan , Olive Lisa , Willmott Catherine , Steer Emma , Berk Michael , Hall Kate 
Published: June 2023

The objective of this systematic scoping review is to understand the extent and scope of evidence regarding neurodiversity in elite sport. This systematic scoping review considered epidemiological studies, commentary and viewpoints papers, systematic review and meta-analyses, and any intervention or clinical treatment, management and practice studies in relation to neurodiversity in elite sport. Case studies and grey literature were ineligible for review. Neurodivergence included neurodevelopmental disorders such as autism spectrum disorder, attention-deficit hyperactivity disorder (ADHD) and specific learning disorders. Elite sport was defined as Olympic, Paralympic, national, international, professional and semiprofessional sport. The final 23 studies included in this review comprised 10 observational studies, 4 systematic/narrative reviews, 6 commentary/position statements and 3 qualitative studies. The literature reflected a major focus on ADHD as a risk factor for concussion and prognosis for postconcussion recovery. Further, there was a focus on the medical management of ADHD, regarding adherence to sporting antidoping regulations. One study focused on the experience of autism in athletes in elite sport settings through qualitative interviews. One study focused on anxiety disorders in elite athletes, with ADHD emerging as a major risk factor. There is a strong rationale for future research to build on the evidence for neurodiversity in elite sport to foster supportive and inclusive elite sporting environments.
Anticoagulant in atrial fibrillation patients with prior intracranial haemorrhage: a meta-analysis
Authors: Cai Huiya , Chen Guoquan , Hu Wei , Jiang Chunjiao 
Published: June 2023

BackgroundThe benefit of resuming anticoagulation in atrial fibrillation (AF) patients with prior intracranial haemorrhage (ICH) and which anticoagulant to choose are controversial.Summary of reviewPubMed, Embase, Web of Science and the Cochrane Library were searched from their inception until 13 February 2022. Thirteen eligible articles (17 600 participants) were collected, including 11 real-world studies (n=17 296) and 2 randomised controlled trials (RCTs) (n=304). Compared with no anticoagulants, oral anticoagulation (OAC) was not associated with an increased risk of ICH recurrence (HR 0.85 (95% CI 0.57 to 1.25), p=0.41), but with a significantly increased risk of major bleeding (HR 1.66 (95% CI 1.20 to 2.30), p<0.01). Meanwhile, OAC was associated with a reduced risk of ischaemic stroke/systemic thromboembolism (IS/SE) (HR 0.54 (95% CI 0.42 to 0.70), p<0.01) and all-cause death (HR 0.38 (95% CI 0.28 to 0.52), p<0.01) compared with no anticoagulants. Furthermore, compared with warfarin, non-vitamin K antagonist oral anticoagulants (NOACs) were associated with a significant reduction of ICH recurrence (HR 0.64 (95% CI 0.49 to 0.85), p<0.01), while the risk of IS/SE and all-cause mortality were comparable between warfarin and NOACs.ConclusionsFor patients with AF with prior ICH, OAC is associated with a significant reduction in IS/SE and all-cause mortality without increasing ICH recurrence, but may increase major bleeding risk. Compared with warfarin, NOACs had a better safety profile and comparable efficacy. Further larger RCTs are warranted to validate these findings.
Respiratory Event-Induced Blood Pressure Oscillations Vary by Sleep Stage in Sleep Apnea Patients
Authors: Chaung Yao Shun , Alex Raichel M. , Jani Mahrshi , Watenpaugh Donald E. , Vilimkova Kahankova Radana , Sands Scott A. , Behbehani Khosrow 
Published: June 2023

Obstructive sleep apnea (OSA) pathologically stresses the cardiovascular system. Apneic events cause significant oscillatory surges in nocturnal blood pressure (BP). Trajectories of these surges vary widely. This variability challenges the quantification, characterization, and mathematical modeling of BP surge dynamics. We present a method of aggregating trajectories of apnea-induced BP surges using a sample-by-sample averaging of continuously recorded BP. We applied the method to recordings of overnight BP (average total sleep time:

4.77
±
1.64

h) for 10 OSA patients (mean AHI: 63.5 events/h; range: 18.3-105.4). We studied surges in blood pressure due to obstructive respiratory events separated from other such events by at least 30 s (274 total events). These events increased systolic (SBP) and diastolic (DBP) BP by

19
±
7.1

mmHg (14.8%) and

11
±
5.6

mmHg (15.5%), respectively, relative to mean values during wakefulness. Further, aggregated SBP and DBP peaks occurred on average 9 s and 9.5 s after apnea events, respectively. Interestingly, the amplitude of the SBP and DBP peaks varied across sleep stages, with mean peak ranging from

128.8
±
12.4

to

166.1
±
15.5

mmHg for SBP and from

63.1
±
8.2

to

84.2
±
9.4

mmHg for DBP. The aggregation method provides a high level of granularity in quantifying BP oscillations from OSA events and may be useful in modeling autonomic nervous system responses to OSA-induced stresses.
Phase Ib/II Study of a Liposomal Formulation of Eribulin (E7389-LF) plus Nivolumab in Patients with Advanced Solid Tumors: Results from Phase Ib
Authors: Ida Hanae , Shimizu Toshio , Nishino Makoto , Nakamura Yoshiaki , Yazaki Shu , Katsuya Yuki , Sato Jun , Koyama Takafumi , Iwasa Satoru , Sudo Kazuki , Kondo Shunsuke , Yonemori Kan , Shitara Kohei , Shiono Satoshi , Matsuoka Daiko , Yasuda Keisuke , Otake Yohei , Suzuki Takuya , Takase Takao , Takashima Shuya , Yamaguchi Kohei , Semba Taro , Yamamoto Noboru 
Published: June 2023

Purpose:
To determine a recommended dose of liposomal eribulin (E7389-LF) in combination with nivolumab in patients with advanced solid tumors, and to evaluate the safety, efficacy, pharmacokinetics, and biomarker impact of this regimen.

Experimental Design:
Japanese patients with advanced, nonresectable, or recurrent solid tumors and no existing alternative standard/effective therapy (except nivolumab monotherapy) were assigned to either E7389-LF 1.7 mg/m2 plus nivolumab 360 mg every 3 weeks, E7389-LF 2.1 mg/m2 plus nivolumab 360 mg every 3 weeks, E7389-LF 1.1 mg/m2 plus nivolumab 240 mg every 2 weeks, or E7389-LF 1.4 mg/m2 plus nivolumab 240 mg every 2 weeks. Primary objectives were to evaluate the safety/tolerability of each dose cohort and to determine the recommended phase II dose (RP2D). Secondary/exploratory objectives, including safety [dose-limiting toxicities (DLT) and adverse events (AE)], pharmacokinetics, efficacy [including objective response rate (ORR)], and biomarker results were used in determining the RP2D.

Results:
Twenty-five patients were enrolled to treatment [E7389-LF 1.7 mg/mg2 every 3 weeks (n = 6), E7389-LF 2.1 mg/m2 every 3 weeks (n = 6), E7389-LF 1.1 mg/m2 every 2 weeks (n = 7), E7389-LF 1.4 mg/m2 every 2 weeks (n = 6)]. Twenty-four patients were evaluated for DLTs, of whom 3 had DLTs (1 at E7389-LF 1.7 mg/m2 every 3 weeks, 1 at 1.1 mg/m2 every 2 weeks, and 1 at 1.4 mg/m2 every 2 weeks). All patients had ≥1 treatment-related treatment-emergent AE (TEAE); 68.0% had ≥1 grade 3–4 treatment-related TEAE. Changes in vasculature and IFN-related biomarkers were seen in each cohort. The overall ORR was 16%.

Conclusions:
E7389-LF plus nivolumab was tolerable overall; the recommended dose for future study was 2.1 mg/m2 plus nivolumab 360 mg every 3 weeks.

Significance:
This phase Ib part of a phase Ib/II study assessed the tolerability and activity of a liposomal formulation of eribulin (E7389-LF) plus nivolumab in 25 patients with advanced solid tumors. The combination was tolerable overall; 4 patients had a partial response. Vasculature and immune-related biomarker levels increased, suggesting vascular remodeling.
Systemic Treatments and Molecular Biomarkers for Perivascular Epithelioid Cell Tumors: A Single-institution Retrospective Analysis
Authors: Testa Stefano , Bui Nam Q. , Ganjoo Kristen N. 
Published: June 2023

Perivascular epithelioid cell tumors (PEComa) are a large family of mesenchymal neoplasms, with variable clinical course. Evidence regarding treatment of advanced PEComas is scarce, with only one FDA-approved treatment available. The goals of this study were to provide data regarding systemic treatments for advanced PEComas and to identify biomarkers of prognostic relevance. This is a single-institution retrospective study of patients with advanced PEComas requiring systemic treatment, including malignant PEComa, angiomyolipoma (including the epithelioid variant), and lymphangioleiomyomatosis. Outcomes measured were overall survival (OS), first-line and combined progression-free survival (PFS), and tumor response. Kaplan–Meier, univariable, and multivariable Cox proportional hazards analysis were performed. A total of 29 patients were included, most with malignant PEComa (n = 17). Median OS was 204.9 months, while median PFS was 92.4 months from first-line, and 15.8 months for all lines combined. TFE3 overexpression correlated with higher risk of death (HR: 11.8, P = 0.04), and shorter median OS (P = 0.001). Chemotherapy and mTOR inhibitors showed similar OS (P = 0.84), and first-line PFS (P = 0.67). Combined PFS was similar between individual mTOR inhibitors, chemotherapy, immune checkpoint inhibitors and other treatments (P = 0.19). Different mTOR inhibitors demonstrated similar efficacy, making cost and availability important considerations when choosing a specific agent. mTOR inhibitors showed similar outcomes as chemotherapy, suggesting that these should be preferred whenever possible for patients with PEComas given the morbidity associated with chemotherapy. TFE3 overexpression highlighted a subgroup of PEComas with worse prognosis and more aggressive behavior.

Significance:
This study examines systemic treatments for advanced PEComas, a rare group of sarcomas, and identifies molecular biomarkers of prognosis. Our results show that mTOR inhibitors have similar efficacy as chemotherapy, and that TFE3 overexpression, on IHC or FISH, correlates with a more aggressive disease course.
Abstract 11036: Aortic Valve Calcification is Associated With an Increased Risk of Mortality in Patients With Low Flow Low Gradient Moderate Aortic Stenosis
Authors: Mogensen Nils Sofus Borg , Carter-Storch Rasmus , Annabi Mohamed-salah , Grenier-Delaney Jasmine , Moller Jacob , Ovrehus Kristian Altern , Pibarot Philippe , Dahl Jordi Sanchez , Clavel Marie-Annick A 
Published: June 2023

Introduction:
Aortic Valve Calcification (AVC) measured by computed tomography (C-CT) and Dobutamine stress echocardiography (DSE) are both important when determining AS severity in low flow low gradient (LFLG) AS. It is generally accepted that AS is moderate if aortic mean gradient is <40mmHg on DSE and AVC is not severe.

However, recent studies suggest that patients with moderate AS may have a worse outcome than expected when treated medically.

Objective:
To examine the correlation between AVC and mortality in patients with LFLG moderate AS on both DSE and C-CT when treated medically.

Method:
88 Patients with LFLG AS (aortic mean gradient <40 mmHg, aortic valve area <1.0 cm
2
& stroke volume index (SVi) <35ml/m
2
) and moderate AS on DSE and C-CT were identified from two prospective studies. AVC ratio was calculated as AVC divided by the sex-specific AVC threshold for severity; 2000 AU in males and 1200 AU in females.

Results:
Optimal threshold of AVC ratio to predict 2-year mortality was 0.68 on ROC-curve (AUC=0.72).Patients were stratified according to AVC ratio: 51 (58%) presented with AVC ratio <0.7 and 37 (42%) with AVC ratio 0.7–1.0. 2 year survival was lower in the latter group (79.5±0.1 vs 46.9±0.1% - Figure 1). Age (78±9 vs 75±11, p=0.32), sex distribution (females 33 vs 41%, p=0.49) and DSE SVi increase (18±24 vs 18±12%, p=0.94) were similar in both groups.

Patients with AVC ratio <0.7 presented with higher LVEF (50±15 vs 44±15%, p=0.08) and lower aortic mean gradient at rest (20±7 vs 23±6 mmHg, p=0.01) and during DSE (21±14 vs 29±15 mmHg, p=0.03).
In univariate Cox regression AVC ratio >0.7 was associated with mortality: HR 2.91 [1.43-5.9], p=0.003. AVC ratio >0.7 remained associated with mortality after adjustment for LVEF, aortic mean gradient, age and sex: HR 2.66 [1.24-5.7], p=0.012. Especially in patients with reduced LVEF: HR 3.47 [1.49-8.09], p=0.004.

Conclusion:
In patients with LFLG moderate AS an AVC ratio > 0.7 is associated with increased risk of mid-term mortality.
Abstract 12170: A National Heart Failure Initiative is Associated With Improved Use of Guideline-Directed Medical Therapies
Authors: Cherkur Sruthi , Kiser Robin Y , Serdynski Lynn , Saunders Rhoda , Sterzing Christina , Macheska Kelly L , Scharnott Michelle C , Bolles Michele M , Chahoud Georges , Mody Kanika , SALTZBERG MITCHELL , Sauer Andrew J , Spencer Steven , Spertus John A , Wald joyce , Fonarow Gregg C , Yancy Clyde W 
Published: June 2023

Background:
Heart Failure (HF) is projected to impact over 8 million people by 2030. Guideline-Directed Medical Therapy (GDMT) reduces mortality and morbidity, but many eligible patients are not receiving the recommended medications. The 2022 ACC/AHA/HFSA Guideline for the Management of HF highlight the importance of SGLT2i and ARNi, which continue to be underused in eligible HFrEF patients.

Methods:
IMPLEMENT-HF (I-HF), a national HF quality improvement initiative focusing on early adoption of GDMT, aims to improve use of SGLT2i and ARNi for HFrEF patients.

I-HF creates a transformative learning collaborative and resource repository across seven U.S regions to promote education and adherence to GDMT, that includes sharing models of clinical care, targeted training, resource development, and quality improvement consultation.
Participation in a learning collaborative allows for sharing of interventions, such as adding SGLT2i on formulary, optimizing EHR tools for GDMT (best practice alerts, disease-specific order sets, dot phrases), provider education, and patient resources to address medication affordability.
Sites receive educational materials, including webinars, pocket guideline booklets, and guideline reminder cards to reinforce GDMT.
Participating hospitals collect GDMT data in Get With The Guidelines®-Heart Failure (GWTG-HF).
ARNi and SGLT2i at discharge was analyzed from baseline (Q1 & Q2 2021 aggregate) through Q1 2022.

Results:
Data from 62 sites (16,533 HF patient records) showed that use of ARNi at hospital discharge increased from baseline 46% to 58% in Q1 2022, +12%,
p
value <0.001. SGLT2i use at discharge increased from 8% to 26%, +18%,
p
value <0.001 (Figure 1).

Conclusions:
Among centers participating in the I-HF initiative, early findings suggest there has been a rapid increase in use of SGLT2i and ARNi at discharge for HFrEF patients. Further study is needed to assess post-discharge GDMT use, adherence, and clinical outcomes.
Abstract 13157: Workplace Culture and Biomarkers of Sympathetic Activation
Authors: hart joy , walker kandi , Shuck Brad , Rai Shesh N , Rai Jayesh , Srivastava Shweta , Srivastava Sanjay , Rai Shesh N , Bhatnagar Aruni , Keith Rachel J 
Published: June 2023

Workplace environment can impact health, but most research has focused on toxic chemicals. Recently, workplace culture—experiences, values, and behaviors unique to a workplace—is studied for its impact on overall health risk; however, connections with robust biologic markers of health remain to be established. Therefore, we examine associations between work environment and urinary levels of catecholamines and their metabolites as biomarkers of sympathetic activation.
In 2018-19, we recruited participants (n=219) from an ongoing CV risk cohort to investigate workplace culture, overall well-being, and stress. Participants completed 7 questionnaires. Clean catch urine samples were used to measure catecholamines and their metabolites. To estimate associations between work and health scales and log or logit-transformed outcomes we used Pearson correlation and linear regression models adjusting for demographics and creatinine.

Participants reporting higher well-being had lower levels of dopamine (DA) (
r
= -0.28), serotonin (5HT) (
r
= -0.17), and 3-methoxytyramine (3MT) (
r
= -0.31), a product of dopamine breakdown. Participants reporting a more engaged workplace had lower levels of DA (
r
= -0.20) and 3MT (
r
= -0.22). Those reporting more positive workplace culture had lower levels of DA (
r
= -0.17) and 3MT (
r
= -0.26) and higher levels of norepinephrine (
r
= 0.19) and 5-hydroxyindole-3-acetic acid (HIAA) (
r
= 0.22). When participants identified more workplace isolation, they had higher levels of DA (
r
= 0.19) and 3MT (
r
= 0.19). Positive workplace culture was correlated with lower levels of DA (
r
= -0.22) and 3MT (
r
= -0.28) and higher levels of HIAA (
r
= 0.22) and homovanillic acid (
r
= 0.20). Given high correlations between catecholamines, we used 3MT for linear regression. In fully adjusted models we found in more positive work cultures, levels of 3MT remained significantly lower (β = -0.065 ±0.025,
p
= 0.01), accounting for 23% of the variance, and a significant positive association between workplace isolation and 3MT (β= 0.064 ±0.030,
p
= 0.04), accounting for 22% of the variance with 3MT, which may reflect greater dopamine degradation. These findings suggest an important relationship between how we work and sympathetic nervous system activity.
Abstract 13711: Cardiomyopathy Complicated by Constriction Resulting in Transplant Listing
Authors: Pietrowicz Rylie , Ibrahim Michel , Hamad Eman A , Rakita Val , Hoosain Jamael 
Published: June 2023

Introduction
We describe a case of severe cardiomyopathy complicated by pericardial constriction resulting from epicardial VT ablation requiring heart transplant listing.

Case Presentation
A 43-year-old with a history of silent MI, LV aneurysm and thrombus, cardiomyopathy (EF 15%), Stage C heart failure, and VT on amiodarone initially presented with symptomatic VT requiring AICD therapy.

He underwent epicardial ablation with no immediate complications. Post-ablation, he developed polymorphic VT prompting LHC revealing new LAD artery stenosis treated with stents. He was discharged on DAPT and warfarin.
He subsequently re-presented with worsening dyspnea, lethargy, and edema. Invasive hemodynamics revealed elevated filling pressures and cardiogenic shock with constrictive physiology. Milrinone and aggressive diuresis were initiated with mild improvement in symptoms. Echocardiogram and cardiac MRI confirmed diagnosis of constrictive pericarditis and presence of hemopericardium.

Discussion
Multidisciplinary discussions were held to determine treatment. Management of constrictive pericarditis with pericardial stripping was considered. The high-risk nature of the procedure with unknown benefit, his age, and now Stage D heart failure made sternotomy a potential increased risk for future cardiac transplant. Ultimately, decision was made for pericardiocentesis, treatment with colchicine, a switch from triple therapy to warfarin and aspirin, and listing for transplant. Surveillance RHC 6 weeks post hospitalization showed resolution of constrictive physiology and normal cardiac output on milrinone.