bluuebunny/crossref_metadata_2025_split huggingface dataset:
Caffeine, Postoperative Delirium And Change In Outcomes after Surgery (CAPACHINOS)-2: protocol for a randomised controlled trial
Authors: Vlisides Phillip E , Ragheb Jacqueline , McKinney Amy , Mentz Graciela , Runstadler Nathan , Martinez Selena , Jewell Elizabeth , Lee UnCheol , Vanini Giancarlo , Schmitt Eva M , Inouye Sharon K , Mashour George A 
Published: May 2023

IntroductionDelirium is a major public health issue for surgical patients and their families because it is associated with increased mortality, cognitive and functional decline, prolonged hospital admission and increased healthcare expenditures. Based on preliminary data, this trial tests the hypothesis that intravenous caffeine, given postoperatively, will reduce the incidence of delirium in older adults after major non-cardiac surgery.Methods and analysisThe CAffeine, Postoperative Delirium And CHange In Outcomes after Surgery-2 (CAPACHINOS-2) Trial is a single-centre, placebo-controlled, randomised clinical trial that will be conducted at Michigan Medicine. The trial will be quadruple-blinded, with clinicians, researchers, participants and analysts all masked to the intervention. The goal is to enrol 250 patients with a 1:1:1: allocation ratio: dextrose 5% in water placebo, caffeine 1.5 mg/kg and caffeine 3 mg/kg as a caffeine citrate infusion. The study drug will be administered intravenously during surgical closure and on the first two postoperative mornings. The primary outcome will be delirium, assessed via long-form Confusion Assessment Method. Secondary outcomes will include delirium severity, delirium duration, patient-reported outcomes and opioid consumption patterns. A substudy analysis will also be conducted with high-density electroencephalography (72-channel system) to identify neural abnormalities associated with delirium and Mild Cognitive Impairment at preoperative baseline.Ethics and disseminationThis study was approved by the University of Michigan Medical School Institutional Review Board (HUM00218290). An independent data and safety monitoring board has also been empanelled and has approved the clinical trial protocol and related documents. Trial methodology and results will be disseminated via clinical and scientific journals along with social and news media.Trial registration numberNCT05574400.
In vitro flow diversion effect of the ReSolv stent with the shelf technique in a bifurcation aneurysm model
Authors: Belanger Brooke L , Morrish Rosalie , McClarty Davis , Barnstable Colette , Muir Warren , Ghazizadeh Soheil , Eesa Muneer , Fiorella David , Wong John H , Sadasivan Chandar , Mitha Alim P 
Published: May 2023

Background
Flow-diverting stents are not currently indicated for the treatment of bifurcation aneurysms, and some case series have demonstrated low occlusion rates, possibly due to a lack in neck coverage. The ReSolv stent is a unique hybrid metal/polymer stent that can be deployed with the shelf technique in order to improve neck coverage.

Methods
A Pipeline, unshelfed ReSolv, and shelfed ReSolv stent were deployed in the left-sided branch of an idealized bifurcation aneurysm model. After determining stent porosity, high-speed digital subtraction angiography runs were acquired under pulsatile flow conditions. Time–density curves were created using two region of interest (ROI) paradigms (total aneurysm and left/right), and four parameters were extracted to characterize flow diversion performance.

Results
The shelfed ReSolv stent demonstrated better aneurysm outflow alterations compared to the Pipeline and unshelfed ReSolv stent when using the total aneurysm as the ROI. On the left side of the aneurysm, there was no significant difference between the shelfed ReSolv stent and the Pipeline. On the right side of the aneurysm, however, the shelfed ReSolv stent had a significantly better contrast washout profile than the unshelfed ReSolv stent and the Pipeline stent.

Conclusions
The ReSolv stent with the shelf technique demonstrates the potential to improve flow diversion outcomes for bifurcation aneurysms. Further in vivo testing will help to determine whether the additional neck coverage leads to better neointimal scaffolding and long-term aneurysm occlusion.
Impedance Response of Insulator Nanoparticle Films with Condensed Chemical Vapor: Structural Isomers and Aprotic Chemicals
Authors: Kano S. , Mekaru H. 
Published: May 2023

Rapid electrical analysis of chemical liquids is a promising technique for on-site evaluation. In this study, the electrical impedance response of insulator nanoparticle films with condensed chemical vapors was investigated in structural isomers and polar aprotic chemical liquids. Headspace vapor was condensed in the nanoscale void between the nanoparticles, and ionic conduction subsequently occurred under an AC voltage. The transient electrical impedance response depends on the vapor pressure and conductivity of the liquid isomers. A chemical liquid of the structural isomers was identified by monitoring the impedance during exposure to its headspace vapor. The response time of the film impedance was 10.6, 4.7, 7.5, and 2.4 s for 1-butanol, 2-butanol, 2-methyl-1-propanol, and tert-butyl alcohol, respectively. Furthermore, the current conduction mechanism in the polar aprotic chemicals was discussed. Although these chemicals did not form molecular networks with the hydrogen bonds, the electrical current flowed in the system. We proposed that hydrogen bonds mediated by water molecules were formed and proton hopping through the condensed polar aprotic liquid occurred. This proposed method has the potential to detect protic and aprotic polar chemical vapors.
Turning Down Oxygen to Turn Up Inflammation in CAFs
Authors: Fuentes Natividad R. , Taniguchi Cullen M. 
Published: May 2023

Abstract
Pancreatic ductal adenocarcinoma (PDAC) contains a desmoplastic stroma that limits blood perfusion and thus the delivery of nutrients, oxygen, and even therapeutics, creating a hypoxic microenvironment that resists nearly all forms of treatment, including immunomodulating therapy. Cancer-associated fibroblasts (CAF) are the main cellular components and producers of stroma in PDAC. Interestingly, CAFs exist as functionally diverse subpopulations derived from distinct lineages, some of which can be either inflammatory (iCAF) or myofibroblastic (myCAF). While previous work has suggested a link between hypoxia and the iCAF phenotype, direct experimental evidence is lacking. In this issue of Cancer Research, Schwörer and colleagues investigate the role of hypoxia and hypoxia-inducible factor-1α (HIF1α) in maintaining fibroblast heterogeneity and promoting tumor progression in PDAC. The authors use a combination of in vitro and orthotopic techniques to identify a strong role for hypoxia in combination with tumor-derived cytokines in maintaining an iCAF phenotype highlighted by IL6 expression. The authors use an innovative in vitro system to simulate oxygen gradients and use these methods to support their assertions regarding hypoxia as a proinflammatory state. These findings suggest that HIF1α promotes the generation of iCAFs, providing novel insight into CAF heterogeneity.
See related article by Schwörer et al., p. 1596
Dying To Find Out: The Cost of Time at the Dawn of the Multicancer Early Detection Era
Authors: Klein Eric A. , Madhavan Sarina , Beer Tomasz M. , Bettegowda Chetan , Liu Minetta C. , Hartman Anne-Renee , Hackshaw Allan 
Published: May 2023

Abstract
Cancer is a significant burden worldwide that adversely impacts life expectancy, quality of life, health care costs, and workforce productivity. Although currently recommended screening tests for individual cancers reduce mortality, they detect only a minority of all cancers and sacrifice specificity for high sensitivity, resulting in a high cumulative rate of false positives. Blood-based multicancer early detection tests (MCED) based on next-generation sequencing (NGS) and other technologies hold promise for broadening the number of cancer types detected in screened populations and hope for reducing cancer mortality. The promise of this new technology to improve cancer detection rates and make screening more efficient at the population level demands the development of novel trial designs that accelerate clinical adoption. Carefully designed clinical trials are needed to address these issues.
Efficacy and Imaging-Enabled Pharmacodynamic Profiling of KRAS G12C Inhibitors in Xenograft and Genetically Engineered Mouse Models of Cancer
Authors: Lee Catherine , Jiang Ziyue Karen , Planken Simon , Manzuk Lisa K. , Ortiz Roberto , Hall Michael , Noorbehesht Kavon , Ram Sripad , Affolter Timothy , Troche Gabriel E. , Ihle Nathan T. , Johnson Theodore , Ahn Youngwook , Kraus Manfred , Giddabasappa Anand 
Published: May 2023

Abstract
KRAS is one of the most commonly mutated oncogenes in lung, colorectal, and pancreatic cancers. Recent clinical trials directly targeting KRAS G12C presented encouraging results for a large population of non–small cell lung cancer (NSCLC), but resistance to treatment is a concern. Continued exploration of new inhibitors and preclinical models is needed to address resistance mechanisms and improve duration of patient responses. To further enable the development of KRAS G12C inhibitors, we present a preclinical framework involving translational, non-invasive imaging modalities (CT and PET) and histopathology in a conventional xenograft model and a novel KRAS G12C knock-in mouse model of NSCLC. We utilized an in-house developed KRAS G12C inhibitor (Compound A) as a tool to demonstrate the value of this framework in studying in vivo pharmacokinetic/pharmacodynamic (PK/PD) relationship and anti-tumor efficacy. We characterized the Kras G12C-driven genetically engineered mouse model (GEMM) and identify tumor growth and signaling differences compared to its Kras G12D-driven counterpart. We also find that Compound A has comparable efficacy to sotorasib in the Kras G12C-driven lung tumors arising in the GEMM, but like observations in the clinic, some tumors inevitably progress on treatment. These findings establish a foundation for evaluating future KRAS G12C inhibitors that is not limited to xenograft studies and can be applied in a translationally relevant mouse model that mirrors human disease progression and resistance.
Atrial Fibrillation Ablation in Young Adults: Measuring Quality of Life Using Patient-Reported Outcomes Over 5 Years
Authors: Johnson Brett M. , Wazni Oussama M. , Farwati Medhat , Saliba Walid I. , Santangeli Pasquale , Madden Ruth , Bouscher Patricia , Chung Mina , Kanj Mohamed , Dresing Thomas J. , Callahan Thomas D. , Bhargava Mandeep , Baranowski Bryan , Rickard John , Cantillon Daniel J. , Tchou Patrick J. , Sroubek Jakub , Nakagawa Hiroshi , Hussein Ayman A. 
Published: May 2023

Background:
Ablation is used for both rhythm control and improved quality of life (QoL) in atrial fibrillation (AF). It has been suggested that young adults may experience high recurrence rates after ablation and data remain lacking regarding QoL benefits. We aimed to investigate AF ablation outcomes and QoL benefits in young adults undergoing AF ablation using a large prospectively maintained registry and automated patient-reported outcomes (PRO).

Methods:
All patients undergoing AF ablation (2013–2016) at our center were prospectively enrolled. Patients aged 50 years or younger were included. For PROs, QoL measures and symptoms were assessed at baseline, 3 months after ablation, and every 6 months thereafter. The AF severity score served as the main assessment of QoL.

Results:

A total of 241 young adults (age, 16–50 years) were included (17% female, 40.3% persistent AF). In all, 77.2% of patients remained arrhythmia-free during the first year of follow-up (80% in nonstructural AF and 66% in structural AF). Using PROs, 90% of patients reported improvement in QoL throughout all survey time points up to 5 years postablation (
P
<0.0001). The baseline median AF severity score was 14 and improved to between 2 and 4 on all follow-up after ablation (
P
<0.0001). Patients also reported fewer and shorter AF episodes, fewer emergency room visits secondary to AF, and fewer hospitalizations (
P
<0.0001).

Conclusions:
Ablation remains an effective rhythm-control strategy in young adults with AF. Young adults also experience significant improvement in QoL with reduction of the frequency and duration of AF episodes and AF-related healthcare utilization.
Progressive Cardiac Metabolic Defects Accompany Diastolic and Severe Systolic Dysfunction in Spontaneously Hypertensive Rat Hearts
Authors: Li Jie , Minczuk Krzysztof , Huang Qiao , Kemp Brandon A. , Howell Nancy L. , Chordia Mahendra D. , Roy R. Jack , Patrie James T. , Qureshi Zoraiz , Kramer Christopher M. , Epstein Frederick H. , Carey Robert M. , Kundu Bijoy K. , Keller Susanna R. 
Published: May 2023

Background
Cardiac metabolic abnormalities are present in heart failure. Few studies have followed metabolic changes accompanying diastolic and systolic heart failure in the same model. We examined metabolic changes during the development of diastolic and severe systolic dysfunction in spontaneously hypertensive rats (SHR).

Methods and Results

We serially measured myocardial glucose uptake rates with dynamic 2‐[
18
F] fluoro‐2‐deoxy‐
d
‐glucose positron emission tomography in vivo in 9‐, 12‐, and 18‐month‐old SHR and Wistar Kyoto rats. Cardiac magnetic resonance imaging determined systolic function (ejection fraction) and diastolic function (isovolumetric relaxation time) and left ventricular mass in the same rats. Cardiac metabolomics was performed at 12 and 18 months in separate rats. At 12 months, SHR hearts, compared with Wistar Kyoto hearts, demonstrated increased isovolumetric relaxation time and slightly reduced ejection fraction indicating diastolic and mild systolic dysfunction, respectively, and higher (versus 9‐month‐old SHR decreasing) 2‐[
18
F] fluoro‐2‐deoxy‐
d
‐glucose uptake rates (Ki). At 18 months, only few SHR hearts maintained similar abnormalities as 12‐month‐old SHR, while most exhibited severe systolic dysfunction, worsening diastolic function, and markedly reduced 2‐[
18
F] fluoro‐2‐deoxy‐
d
‐glucose uptake rates. Left ventricular mass normalized to body weight was elevated in SHR, more pronounced with severe systolic dysfunction. Cardiac metabolite changes differed between SHR hearts at 12 and 18 months, indicating progressive defects in fatty acid, glucose, branched chain amino acid, and ketone body metabolism.

Conclusions
Diastolic and severe systolic dysfunction in SHR are associated with decreasing cardiac glucose uptake, and progressive abnormalities in metabolite profiles. Whether and which metabolic changes trigger progressive heart failure needs to be established.
Sodium‐Glucose Cotransporter‐2 Inhibitor Prevents Stroke in Patients With Diabetes and Atrial Fibrillation
Authors: Chang Sheng‐Nan , Chen Jien‐Jiun , Huang Pang‐Shuo , Wu Cho‐Kai , Wang Yi‐Chih , Hwang Juey‐Jen , Tsai Chia‐Ti 
Published: May 2023

Background

Atrial fibrillation (AF) is associated with increasing risk of thromboembolic or ischemic stroke. The CHA
2
DS
2
‐VASc score is a well‐established predictor of AF stroke. Patients with AF have an increased risk of stroke if they have diabetes. Use of sodium‐glucose cotransporter‐2 inhibitor (SGLT2i) has been shown to be associated with favorable cardiovascular outcomes in patients with diabetes. It was unknown whether use of SGLT2i decreased stroke risk in patients with AF who have diabetes.

Methods and Results

A total of 9116 patients with AF and diabetes from the National Taiwan University historical cohort were longitudinally followed up for 5 years (January 2016–December 2020). The risk of stroke related to SGLT2i use was evaluated by Cox model, adjusting CHA
2
DS
2
‐VASc score in the propensity score–matched population with 474 SGLT2i users and 3235 nonusers. Adverse thromboembolic end points during follow‐up were defined as ischemic stroke. The mean age was 73.2±10.5 years, and 61% of patients were men. There were no significant differences of baseline characteristics between users and nonusers of SGLT2i, including CHA
2
DS
2
‐VASc score in the propensity score–matched population. The stroke rate was 3.4% (95% CI, 2.8–4.2) patient‐years in SGLT2i users and 4.3% (95% CI, 4.0–4.6) in nonusers (
P
=0.021). SGLT2i users had a 20% reduction of stroke (hazard ratio, 0.80 [95% CI, 0.64–0.99];
P
=0.043) after adjustment for the CHA
2
DS
2
‐VASc score.

Conclusions
Use of SGLT2i was associated with a lower stroke risk in patients with diabetes and AF, and it may be considered to escalate SGLT2i to the first‐line treatment in patients with diabetes and AF.
Hemodynamic Effects of Ketone Bodies in Patients With Pulmonary Hypertension
Authors: Nielsen Roni , Christensen Kristian Hylleberg , Gopalasingam Nigopan , Berg‐Hansen Kristoffer , Seefeldt Jacob , Homilius Casper , Boedtkjer Ebbe , Andersen Mads Jønsson , Wiggers Henrik , Møller Niels , Bøtker Hans Erik , Mellemkjær Søren 
Published: May 2023

Background
Pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) are debilitating diseases with a high mortality. Despite emerging treatments, pulmonary vascular resistance frequently remains elevated. However, the ketone body 3‐hydroxybutyrate (3‐OHB) may reduce pulmonary vascular resistance in these patients. Hence, the aim was to assess the hemodynamic effects of 3‐OHB in patients with PAH or CTEPH.

Methods and Results

We enrolled patients with PAH (n=10) or CTEPH (n=10) and residual pulmonary hypertension. They received 3‐OHB infusion and placebo (saline) for 2 hours in a randomized crossover study. Invasive hemodynamic and echocardiography measurements were performed. Furthermore, we investigated the effects of 3‐OHB on the right ventricle of isolated hearts and isolated pulmonary arteries from Sprague–Dawley rats. Ketone body infusion increased circulating 3‐OHB levels from 0.5±0.5 to 3.4±0.7 mmol/L (
P
<0.001). Cardiac output improved by 1.2±0.1 L/min (27±3%,
P
<0.001), and right ventricular annular systolic velocity increased by 1.4±0.4 cm/s (13±4%,
P
=0.002). Pulmonary vascular resistance decreased by 1.3±0.3 Wood units (18%±4%,
P
<0.001) with no significant difference in response between patients with PAH and CTEPH. In the rat studies, 3‐OHB administration was associated with decreased pulmonary arterial tension compared with saline administration (maximal relative tension difference: 12±2%,
P
<0.001) and had no effect on right ventricular systolic pressures (
P
=0.63), whereas pressures rose at a slower pace (dP/dtmax,
P
=0.02).

Conclusions
In patients with PAH or CTEPH, ketone body infusion improves cardiac output and decreases pulmonary vascular resistance. Experimental rat studies support that ketone bodies relax pulmonary arteries. Long‐term studies are warranted to assess the clinical role of hyperketonemia.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT04615754.
Feasibility of Lipid Screening During First Trimester of Pregnancy to Identify Women at Risk of Severe Dyslipidemia
Authors: Golwala Sohil , Dolin Cara D. , Nemiroff Richard , Soffer Daniel , Denduluri Srinivas , Jacoby Douglas , Lewey Jennifer 
Published: May 2023

Background
Dyslipidemia is an important risk factor for atherosclerotic cardiovascular disease, especially when disease presents at a young age. Despite national screening guidelines to perform a lipid profile test in children and young adults, many reproductive‐age women have not undergone lipid screening. Our objective was to assess the feasibility of lipid screening during the first trimester of pregnancy as a strategy to increase lipid screening rates among women receiving prenatal care.

Methods and Results
A nonfasting lipid panel was incorporated into routine prenatal care among obstetricians at a single academic clinic. Educational materials and a clinical referral pathway were developed for patients with abnormal results. Over 6 months, 445 patients had a first prenatal care visit. Of the 358 patients who completed laboratory testing, 236 (66%) patients completed lipid testing. Overall, 59 (25%) patients had abnormal results. One patient with previously undiagnosed suspected familial hypercholesterolemia was identified. Barriers to ordering lipid tests included the burden of reviewing additional laboratory results and uncertainty about patient counseling.

Conclusions
Implementation of nonfasting lipid screening as part of routine prenatal care during the first trimester is feasible and may play a crucial role in timely diagnosis and management of lipid disorders in women of reproductive age. Future work should focus on optimizing health system workflow to minimize burden on clinical staff and facilitate follow‐up with appropriate specialists.
Hospital Procedural Volume and Clinical Outcomes Following Septal Reduction Therapy in Obstructive Hypertrophic Cardiomyopathy
Authors: Altibi Ahmed M. , Ghanem Fares , Zhao Yuanzi , Elman Miriam , Cigarroa Joaquin , Nazer Babak , Song Howard K. , Masri Ahmad 
Published: May 2023

Background
Prior national data showed a substantial in‐hospital mortality in septal myectomy (SM) with an inverse volume–outcomes relationship. This study sought to assess the contemporary outcomes of septal reduction therapy and volume–outcome relationship in obstructive hypertrophic cardiomyopathy.

Methods and Results

All septal reduction therapy admissions between 2010 to 2019 in the United States were analyzed using the National Readmission Databases. Hospitals were stratified into tertiles of low‐, medium‐, and high‐volume based on annualized procedural volume of alcohol septal ablation and SM. Of 19 007 patients with obstructive hypertrophic cardiomyopathy who underwent septal reduction therapy, 12 065 (63%) had SM. Two‐thirds of hospitals performed ≤5 SM or alcohol septal ablation annually. In all SM encounters, 482 patients (4.0%) died in‐hospital post‐SM. In‐hospital mortality was <1% in 1505 (88.4%) hospitals, 1% to 10% in 30 (1.8%) hospitals, and ≥10% in 167 (9.8%) hospitals. There were 63 (3.7%) hospitals (averaging 2.2 SM cases/year) with 100% in‐hospital mortality. Post‐SM (in low‐, medium‐, and high‐volume centers, respectively), in‐hospital mortality (5.7% versus 3.9% versus 2.4%,
P
=0.003; adjusted odds ratio [aOR], 2.86 [95% CI, 1.70–4.80],
P
=0.001), adverse in‐hospital events (21.30% versus 18.0% versus 12.6%,
P
=0.001; aOR, 1.88 [95% CI, 1.45–2.43],
P
=0.001), and 30‐day readmission (17.1% versus 12.9% versus 9.7%,
P
=0.001; adjusted hazard ratio, 1.53 [95% CI, 1.27–1.96],
P
=0.001) were significantly higher in low‐ versus high‐volume hospitals. For alcohol septal ablation, the incidence of in‐hospital death and all other outcomes did not differ by hospital volume.

Conclusions
In‐hospital SM mortality was 4% with an inverse volume‐mortality relationship. Mortality post‐alcohol septal ablation was similar across all volume tertiles. Morbidity associated with SM was substantial across all volume tertiles.