bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of DNA Repair Inhibitor Response in Short-Term Patient-Derived Ovarian Cancer Organoids
Authors: Hill Sarah J. , Decker Brennan , Roberts Emma A. , Horowitz Neil S. , Muto Michael G. , Worley Michael J. , Feltmate Colleen M. , Nucci Marisa R. , Swisher Elizabeth M. , Nguyen Huy , Yang Chunyu , Morizane Ryuji , Kochupurakkal Bose S. , Do Khanh T. , Konstantinopoulos Panagiotis A. , Liu Joyce F. , Bonventre Joseph V. , Matulonis Ursula A. , Shapiro Geoffrey I. , Berkowitz Ross S. , Crum Christopher P. , D'Andrea Alan D. 
Published: September 2018

Abstract
Based on genomic analysis, 50% of high-grade serous ovarian cancers (HGSC) are predicted to have DNA repair defects. Whether this substantial subset of HGSCs actually have functional repair defects remains unknown. Here, we devise a platform for functional profiling of DNA repair in short-term patient-derived HGSC organoids. We tested 33 organoid cultures derived from 22 patients with HGSC for defects in homologous recombination (HR) and replication fork protection. Regardless of DNA repair gene mutational status, a functional defect in HR in the organoids correlated with PARP inhibitor sensitivity. A functional defect in replication fork protection correlated with carboplatin and CHK1 and ATR inhibitor sensitivity. Our results indicate that a combination of genomic analysis and functional testing of organoids allows for the identification of targetable DNA damage repair defects. Larger numbers of patient-derived organoids must be analyzed to determine whether these assays can reproducibly predict patient response in the clinic.
Significance: Patient-derived ovarian tumor organoids grow rapidly and match the tumors from which they are derived, both genetically and functionally. These organoids can be used for DNA repair profiling and therapeutic sensitivity testing and provide a rapid means of assessing targetable defects in the parent tumor, offering more suitable treatment options. Cancer Discov; 8(11); 1404–21. ©2018 AACR.
This article is highlighted in the In This Issue feature, p. 1333
Efficacy of Endocardial Ablation of Drug-Resistant Ventricular Fibrillation in Brugada Syndrome
Authors: Talib Ahmed Karim , Takagi Masahiko , Shimane Akira , Nakano Makoto , Hayashi Tatsuya , Okajima Katsunori , Kentaro Minami , Fukada Koji , Kowase Shinya , Kurosaki Kenji , Nitta Junichi , Nishizaki Mitsushiro , Yui Yoshiaki , Talib Ali , Sato Nobuyuki , Kawamura Yuichiro , Hasebe Naoyuki , Aita Satoshi , Sai Eikou , Komatsu Yuki , Kuroki Kenji , Kaneshiro Takashi , Dongzu Xu , Tajiri Kazuko , Igarashi Miyako , Yamasaki Hiro , Murakoshi Nobuyuki , Kumagai Koji , Sekiguchi Yukio , Nogami Akihiko , Aonuma Kazutaka 
Published: September 2018

Background
Both endocardial trigger elimination and epicardial substrate modification are effective in treating ventricular fibrillation (VF) in Brugada syndrome. However, the primary approach and the characteristics of patients who respond to endocardial ablation remain unknown.

Methods
Among 123 symptomatic Brugada syndrome patients (VF, 63%; syncope, 37%), ablation was performed in 21 VF/electrical storm patients, the majority of whom were resistant to antiarrhythmic drugs.

Results

Careful endocardial mapping revealed that 81% of the patients had no specific findings, whereas 19% of the patients, who experienced the most frequent VF episodes with notching of the QRS in lead V
1
, had delayed low-voltage fractionated endocardial electrograms. Ablation of VF triggers followed by endocardial substrate modification was performed in the right ventricular outflow tract in 85% of the cases and in the right ventricle in 15%. VF triggers could not be completely eliminated in 1 patient and VF became noninducible in 14 (88%) patients among 16 patients who underwent VF induction with normalization of Brugada-type ECG in 3. During follow-up (56.14±36.95 months), VF recurrence was observed in 7 patients. Importantly, all patients who had nothing of QRS in lead V
1
did not respond to endocardial ablation despite presence of VF-triggering ectopic beats during ablation.

Conclusions

With careful documentation of VF-triggering ectopic beats and detailed endocardial mapping, endocardial VF trigger elimination followed by endocardial substrate modification has an excellent long-term outcome, whereas presence of QRS notching in lead V
1
was associated with high VF recurrence suggesting epicardial substrate ablation as effective initial approach.
Outcome of Cardiac Sarcoidosis Presenting With High-Grade Atrioventricular Block
Authors: Nordenswan Hanna-Kaisa , Lehtonen Jukka , Ekström Kaj , Kandolin Riina , Simonen Piia , Mäyränpää Mikko , Vihinen Tapani , Miettinen Heikki , Kaikkonen Kari , Haataja Petri , Kerola Tuomas , Rissanen Tuomas T. , Kokkonen Jorma , Alatalo Aleksi , Pietilä-Effati Päivi , Utriainen Seppo , Kupari Markku 
Published: September 2018

Background:
Symptomatic high-grade atrioventricular block (AVB) is the most common and often the only presenting manifestation (lone AVB) of cardiac sarcoidosis. Implantation of an intracardiac cardioverter defibrillator instead of a pacemaker is recommended, but the true risk of fatal arrhythmia, one incident to lone AVB in particular, remains poorly known.

Methods:
We used Myocardial Inflammatory Diseases in Finland Study Group Registry to analyze the presentations, left ventricular (LV) function, pacemaker therapy, and ventricular arrhythmias in cardiac sarcoidosis. From year 1988 to 2015, altogether 325 cases of cardiac sarcoidosis were diagnosed in Finland. Of them, 143 patients (112 women, mean age 52 years) presented with Mobitz II second degree or third degree AVB in the absence of other explanatory cardiac disease.

Results:

Concomitant with AVB at presentation, 20 patients had either ventricular tachycardia or severe LV dysfunction with ejection fraction <35% and 29 patients had nonsevere LV dysfunction (ejection fraction, 35%–50%) while 90 patients presented with AVB alone. During a median of 2.8 years’ follow-up, 23 sudden cardiac deaths (fatal or aborted) and 19 ventricular tachycardias were recorded as arrhythmic end point events. Their composite 5-year incidence (95% confidence interval) was 56% (36%–88%) in the AVB subgroup with ventricular tachycardia or severe LV dysfunction versus 24% (12%–49%) in the subgroup with nonsevere LV dysfunction and 24% (15%–38%) with lone AVB (
P
=0.019). The 5-year incidence of sudden cardiac death was 34% (16%–71%), 14% (6%–35%), and 9% (4%–22%) in the respective subgroups (
P
=0.060).

Conclusions:
The risk of sudden cardiac death is significant in cardiac sarcoidosis presenting with high-grade AVB with or without ventricular tachycardia or LV dysfunction. The consensus recommendation to implant an intracardiac cardioverter defibrillator whenever permanent pacing is needed seems well-founded.
Home-Delivered Meals Postdischarge From Heart Failure Hospitalization
Authors: Hummel Scott L. , Karmally Wahida , Gillespie Brenda W. , Helmke Stephen , Teruya Sergio , Wells Joanna , Trumble Erika , Jimenez Omar , Marolt Cara , Wessler Jeffrey D. , Cornellier Maria L. , Maurer Mathew S. 
Published: September 2018

Background
In patients with heart failure (HF), malnutrition and dietary sodium excess are common and may worsen outcomes. No prior studies have provided low-sodium, nutritionally complete meals following HF hospitalization.

Methods and Results

The GOURMET-HF study (Geriatric Out-of-Hospital Randomized Meal Trial in Heart Failure) randomized patients discharged from HF hospitalization to 4 weeks of home-delivered sodium-restricted Dietary Approaches to Stop Hypertension meals (DASH/SRD; 1500 mg sodium/d) versus usual care. The primary outcome was the between-group change in the Kansas City Cardiomyopathy Questionnaire summary score from discharge to 4 weeks postdischarge. Additional outcomes included changes in the Kansas City Cardiomyopathy Questionnaire clinical summary score and cardiac biomarkers. All patients were followed 12 weeks for death/all-cause readmission and potential diet-related adverse events (symptomatic hypotension, hyperkalemia, acute kidney injury). Sixty-six patients were randomized 1:1 at discharge to DASH/SRD versus usual care (age, 71±8 years; 30% female; ejection fraction, 39±18%). The Kansas City Cardiomyopathy Questionnaire summary score increased similarly between groups (DASH/SRD 46±23–59±20 versus usual care 43±19–53±24;
P
=0.38), but the Kansas City Cardiomyopathy Questionnaire clinical summary score increase tended to be greater in DASH/SRD participants (47±22–65±19 versus 45±20–55±26;
P
=0.053). Potentially diet-related adverse events were uncommon; 30-day HF readmissions (11% versus 27%;
P
=0.06) and days rehospitalized within that timeframe (17 versus 55;
P
=0.055) trended lower in DASH/SRD participants.

Conclusions
Home-delivered DASH/SRD after HF hospitalization appeared safe in selected patients and had directionally favorable effects on HF clinical status and 30-day readmissions. Larger studies are warranted to clarify the effects of postdischarge nutritional support in patients with HF.

Clinical Trial Registration

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT02148679.
Impact of Epicardial Adipose Tissue, Left Ventricular Myocardial Fat Content, and Interstitial Fibrosis on Myocardial Contractile Function
Authors: Ng Arnold C.T. , Strudwick Mark , van der Geest Rob J. , Ng Austin C.C. , Gillinder Lisa , Goo Shi Yi , Cowin Gary , Delgado Victoria , Wang William Y.S. , Bax Jeroen J. 
Published: September 2018

Background
Current understanding of metabolic heart disease consists of a myriad of different pathophysiological mechanisms. Epicardial adipose tissue (EAT) is increasingly recognized as metabolically active and associated with adverse cardiovascular outcomes. The present study aimed to investigate the effect of increased EAT volume index on left ventricular (LV) myocardial fat content and burden of interstitial myocardial fibrosis and their subsequent effects on LV myocardial contractile function.

Methods and Results

A total of 40 volunteers (mean age, 35±10 years; 26 males) of varying body mass index (25.0±4.1 kg/m
2
; range, 19.3–36.3 kg/m
2
) and without diabetes mellitus or hypertension were prospectively recruited. EAT volume index, LV myocardial fat content, and extracellular volume were quantified by magnetic resonance imaging. LV myocardial contractile function was quantified by speckle tracking echocardiography global longitudinal strain on the same day as magnetic resonance imaging examination. Mean total EAT volume index, LV myocardial fat content, and extracellular volume were 30.0±19.6 cm
3
/m
2
, 5.06%±1.18%, and 27.5%±0.5%, respectively. On multivariable analyses, increased EAT volume index and insulin resistance were independently associated with both increased LV myocardial fat content content and higher burden of interstitial myocardial fibrosis. Furthermore, increased EAT volume index was independently associated with LV global longitudinal strain.

Conclusions
Increased EAT volume index and insulin resistance were independently associated with increased myocardial fat accumulation and interstitial myocardial fibrosis. Increased EAT volume index was associated with detrimental effects on myocardial contractile function as evidenced by a reduction in LV global longitudinal strain.
Comparison of Vascular Closure Devices Versus Manual Compression After Femoral Artery Puncture in Women
Authors: Gewalt Senta M. , Helde Sandra M. , Ibrahim Tareq , Mayer Katharina , Schmidt Roland , Bott-Flügel Lorenz , Hoppe Katharina , Ott Ilka , Hieber Julia , Morath Tanja , Byrne Robert A. , Kufner Sebastian , Cassese Salvatore , Hoppmann Petra , Fusaro Massimiliano , Schunkert Heribert , Laugwitz Karl-Ludwig , Kastrati Adnan , Schüpke Stefanie ,   for the Instrumental Sealing of Arterial Puncture Site—CLOSURE Device Versus Manual Compression (ISAR-CLOSURE) Trial Investigators
Published: September 2018

Background:
The value of vascular closure devices (VCD) in women undergoing transfemoral catheterization has not been sufficiently investigated.

Methods and Results:

This is a sex-specific analysis of 1395 women enrolled in a large-scale, randomized, multicenter trial, in which patients undergoing transfemoral diagnostic coronary angiography were randomly assigned in a 1:1:1 ratio to arteriotomy closure with an intravascular VCD, extravascular VCD, or manual compression (MC). Primary objective was to assess the safety and efficacy of 2 different VCD compared with MC regarding vascular access-site complications at 30 days. A secondary comparison was between 2 different types of contemporary VCD. Overall, women were at higher risk for vascular access-site complications compared with men (9.0% versus 6.4%;
P
=0.002). Vascular access-site complications were comparable in women assigned to VCD and MC (8.6% versus 9.8%;
P
=0.451). There was no interaction of treatment effect and sex (
P
interaction
=0.970). Time to hemostasis was significantly shortened with VCD compared with MC (1 [interquartile range, 0.5–2.0] minutes) versus 11 [interquartile range, 10–15] minutes;
P
<0.001); however, more women with VCD required repeat MC (2.4% versus 0.6%;
P
=0.018). The use of the intravascular compared with the extravascular VCD was associated with a numerical reduction in vascular access-site complications (6.6% versus 10.7%;
P
=0.027) and significant reductions in time to hemostasis and VCD failure.

Conclusions:
In women undergoing diagnostic coronary angiography via the common femoral artery, VCD and MC provided comparable safety, while time to hemostasis was reduced with VCD.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT01389375.
The Extent of Aortic Atherosclerosis Predicts the Occurrence, Severity, and Recovery of Acute Kidney Injury After Transcatheter Aortic Valve Replacement
Authors: Shishikura Daisuke , Kataoka Yu , Pisaniello Anthony D. , Delacroix Sinny , Montarello Joseph K. , Nicholls Stephen J. , Worthley Stephen G. 
Published: September 2018

Background:
Acute kidney injury (AKI) can be a major complication of transcatheter aortic valve replacement (TAVR). Atheroembolization of debris during catheter manipulation has been considered as a potential factor causing AKI. This study investigates the impact of aortic atheroma burden on AKI post-TAVR and evaluates the potential of preoperative multislice computed tomographic (MSCT) imaging for the assessment of AKI in these patients.

Methods and Results:

Preoperative multislice computed tomographic images were analyzed in 278 patients with symptomatic severe aortic stenosis who underwent TAVR. AKI was defined as an absolute increase in serum creatinine ≥0.3 mg/dL. Aorta vessel and lumen areas in each 1-mm cross-sectional image were measured. Percent atheroma volume above (PAV
above renal arteries
) and below (PAV
below renal arteries
) renal arteries were calculated by the following formula: PAV={Σ (vessel area−lumen area)/Σ(vessel area)}×100. AKI occurred in 92 patients (33.1%) after TAVR. AKI was associated with a greater PAV above (30.4±8.2 versus 21.3±5.8%;
P
=0.02) but not below (28.9±7.7 versus 25.8±6.1%;
P
=0.41) the renal arteries. Greater PAV
above renal arteries
was associated directly with AKI severity (
P
=0.008) and inversely with recovery in serum creatinine level from peak to discharge (
r
=0.78;
P
=0.002). Multivariate analysis demonstrated that PAV
above renal arteries
was a significant predictor of AKI (
P
=0.02). Receiver-operating curve analysis identified PAV
above renal arteries
>29.5% as an optimal threshold to predict AKI.

Conclusions:
Suprarenal aortic atheroma burden is associated with the occurrence, severity, and recovery of AKI after TAVR. This highlights the utility of preoperative assessment of aortic atherosclerosis on multislice computed tomography to identify patients at high-risk for AKI.
Intentional Fracture of Bioprosthetic Valve Frames in Patients Undergoing Valve-in-Valve Transcatheter Pulmonary Valve Replacement
Authors: Shahanavaz Shabana , Asnes Jeremy D. , Grohmann Jochen , Qureshi Athar M. , Rome Jonathan J. , Tanase Daniel , Crystal Matthew A. , Latson Larry A. , Morray Brian H. , Hellenbrand William , Balzer David T. , Gewillig Marc , Love Jon C. , Berdjis Farhouch , Gillespie Matthew J. , McElhinney Doff B. 
Published: September 2018

Background:
Percutaneous transcatheter pulmonary valve replacement (TPVR) has good clinical and hemodynamic outcomes in treating dysfunctional bioprosthetic valves (BPV) in the pulmonary position. Valve-in-valve therapy can further decrease the inner diameter (ID), potentially resulting in patient-prosthesis mismatch in patients with smaller BPVs.

Methods and Results:

To evaluate feasibility and outcomes of intentional BPV fracture to enlarge the pulmonary valve orifice with TPVR, 37 patients from 13 centers who underwent TPVR with intended BPV fracture were evaluated. A control cohort (n=70) who underwent valve-in-valve TPVR without attempted fracture was evaluated. BPV was successfully fractured in 28 patients and stretched in 5 while fracture was unsuccessful in 4. A Melody valve was implanted in 25 patients with fractured/stretched frame and a Sapien (XT 3) valve in 8. Among patients whose BPV was fractured/stretched, the final ID was a median of 2 mm larger (0–6.5 mm) than the valve’s true ID. The narrowest diameter after TPVR in controls was a median of 2 mm smaller (
P
<0.001) than true ID. Right ventricular outflow tract gradient decreased from median 40 to 8 mm Hg in the fracture group. Cases with fracture/stretching were matched 1:1 (weight, true ID) to controls. Post-TPVR peak gradient was lower but not significant (8.3±5.2 versus 11.8±9.2 mm Hg;
P
=0.070). There were no fracture-related adverse events.

Conclusions:
Preliminary experience shows intentional fracture of BPV frame can be useful for achieving larger ID and better hemodynamics after valve-in-valve TPVR.
Hypothyroidism Is Associated With Coronary Endothelial Dysfunction in Women
Authors: Sara Jaskanwal D. , Zhang Ming , Gharib Hossein , Lerman Lilach O. , Lerman Amir 
Published: September 2018

Background
Hypothyroidism is associated with an increased risk of coronary artery disease, beyond that which can be explained by its association with conventional cardiovascular risk factors. Coronary endothelial dysfunction precedes atherosclerosis, has been linked to adverse cardiovascular events, and may account for some of the increased risk in patients with hypothyroidism. The aim of this study was to determine whether there is an association between epicardial and microvascular coronary endothelial dysfunction and hypothyroidism.

Methods and Results

In 1388 patients (mean age 50.5 [12.3] years, 34% male) presenting with stable chest pain to Mayo Clinic, Rochester,
MN
for diagnostic coronary angiography, and who were found to have nonobstructive coronary artery disease (<40% stenosis), we invasively assessed coronary artery endothelial‐dependent microvascular and epicardial function by evaluating changes in coronary blood flow (% Δ
CBF
Ach) and diameter (% Δ
CAD
Ach), respectively, in response to intracoronary infusions of acetylcholine. Patients were divided into 2 groups: hypothyroidism, defined as a documented history of hypothyroidism or a thyroid‐stimulating hormone (
TSH
) >10.0
mU
/
mL
, n=188, and euthyroidism, defined as an absence of a history of hypothyroidism in the clinical record and/or 0.3<
TSH
≤10.0
mU
/
mL
, n=1200. Subjects with a history of hypothyroidism had a significantly lower % Δ
CBF
Ach (48.26 [80.66] versus 64.58 [128.30]) compared to patients with euthyroidism, while the % Δ
CAD
Ach did not vary significantly between groups. After adjusting for covariates, females with hypothyroidism still had a significantly lower % Δ
CBF
Ach (estimated difference in % Δ
CBF
Ach [
SE
]: −16.79 [8.18]).

Conclusions
Hypothyroidism in women is associated with microvascular endothelial dysfunction, even after adjusting for confounders, and may explain some of the increased risk of cardiovascular disease in these patients.
Midlife Cardiovascular Risk Factors and Late‐Life Unrecognized and Recognized Myocardial Infarction Detect by Cardiac Magnetic Resonance: ICELAND‐MI, the AGES‐Reykjavik Study
Authors: McAreavey Dorothea , Vidal Jean‐Sébastien , Aspelund Thor , Eiriksdottir Gudny , Schelbert Erik B. , Kjartansson Olafur , Cao Jie J. , Thorgeirsson Gudmundur , Sigurdsson Sigurdur , Garcia Melissa , Harris Tamara B. , Launer Lenore J. , Gudnason Vilmundur , Arai Andrew E. 
Published: September 2018

Background

Associations of atherosclerosis risk factors with unrecognized myocardial infarction (
UMI
) are unclear. We investigated associations of midlife risk factors with
UMI
and recognized
MI
(
RMI
) detected 31 years later by cardiac magnetic resonance.

Methods and Results

The Reykjavik Study (1967–1991) collected serial risk factors in subjects, mean (
SD
) age 48 (7) years. In
ICELAND
‐
MI
(2004–2007), 936 survivors (76 (5) years) were evaluated by cardiac magnetic resonance. Analysis included logistic regression and random effects modeling. Comparisons are relative to subjects without
MI
. At baseline midlife evaluation, a modified Framingham risk score was significantly higher in
RMI
and in
UMI
versus no
MI
(7.4 (6.3)%; 7.1 (6.2)% versus 5.4 (5.8)%,
P
<0.001).
RMI
and
UMI
were more frequent in men (65%, 64% versus 43%;
P
<0.0001). Baseline systolic and diastolic blood pressure were significantly higher in
UMI
(138 (17) mm Hg versus 133 (17) mm Hg;
P
<0.006; 87 (10) mm Hg versus 84 (10) mm Hg;
P
<0.02). Diastolic
BP
was significantly higher in
RMI
(88 (10) mm Hg versus 84 (10) mm Hg;
P
<0.02). Cholesterol and triglycerides were significantly higher in
RMI
(6.7 (1.1) mmol/L versus 6.2 (1.1) mmol/L;
P
=0.0005; and 1.4 (0.7) mmol/L versus 1.1 (0.7) mmol/L;
P
<0.003). Cholesterol trended higher in
UMI
(
P
=0.08). Serial midlife systolic
BP
was significantly higher in
UMI
versus no
MI
(β [
SE
] = 2.69 [1.28] mm Hg,
P
=0.04). Serial systolic and diastolic
BP
were significantly higher in
RMI
versus no
MI
(4.12 [1.60] mm Hg,
P
=0.01 and 2.05 [0.91] mm Hg,
P
=0.03) as were cholesterol (0.43 [0.11] mmol/L,
P
=0.0001) and triglycerides (0.3 [0.06] mmol/L,
P
<0.0001).

Conclusions

Midlife vascular risk factors are associated with
UMI
and
RMI
detected by cardiac magnetic resonance 31 years later. Systolic blood pressure was the most significant modifiable risk factor associated with later
UMI
.