bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relevance of Platinum-free Interval and BRCA Reversion Mutations for Veliparib Monotherapy after Progression on Carboplatin/Paclitaxel for gBRCA Advanced Breast Cancer (BROCADE3 Crossover)
Authors: Puhalla Shannon L. , Diéras Véronique , Arun Banu K. , Kaufman Bella , Wildiers Hans , Han Hyo S. , Ayoub Jean-Pierre , Stearns Vered , Yuan Yuan , Helsten Teresa , Riley-Gillis Bridget , Murphy Erin , Kundu Madan G. , Wu Meijing , Maag David , Ratajczak Christine K. , Ramathal Cyril Y. , Friedlander Michael 
Published: June 2021

Abstract

Purpose:
Safety, efficacy, and exploratory biomarker analyses were evaluated in patients with advanced HER2-negative germline breast cancer susceptibility gene (gBRCA)-associated breast cancer enrolled in the BROCADE3 trial who received crossover veliparib monotherapy after disease progression on placebo plus carboplatin/paclitaxel.

Patients and Methods:
Eligible patients (N = 513) were randomized 2:1 to veliparib plus carboplatin/paclitaxel or placebo plus carboplatin/paclitaxel; patients had variable platinum-free intervals (PFI) at progression. In the placebo arm, patients were eligible to receive crossover veliparib monotherapy (300–400 mg twice daily continuous). Antitumor activity and adverse events were assessed during crossover veliparib treatment. BRCA reversion mutations at crossover were analyzed retrospectively using next-generation sequencing on plasma circulating tumor DNA (ctDNA).

Results:
Seventy-five patients in the placebo plus carboplatin/paclitaxel arm received ≥1 dose of crossover veliparib postprogression (mean treatment duration: 154 days). Eight of 50 (16%) patients with measurable disease had a RECIST v1.1 response. Activity was greater in patients with PFI ≥180 days compared with &lt;180 days [responses in 23.1% (3/13) vs. 13.5% (5/37) of patients]. BRCA reversion mutations that restored protein function were detected in ctDNA from 4 of 28 patients tested, and the mean duration of crossover veliparib monotherapy was &lt;1 month in these 4 patients versus 7.49 months in patients lacking reversion mutations. The most frequent adverse events were nausea (61%), vomiting (29%), and fatigue (24%).

Conclusions:
Crossover veliparib monotherapy demonstrated limited antitumor activity in patients who experienced disease progression on placebo plus carboplatin/paclitaxel. PFI appeared to affect veliparib activity. BRCA reversion mutations may promote cross-resistance and limit veliparib activity following progression on platinum.
The Prognostic Potential of Human Prostate Cancer-Associated Macrophage Subtypes as Revealed by Single-Cell Transcriptomics
Authors: Siefert Joseph C. , Cioni Bianca , Muraro Mauro J. , Alshalalfa Mohammed , Vivié Judith , van der Poel Henk G. , Schoots Ivo G. , Bekers Elise , Feng Felix Y. , Wessels Lodewyk F.A. , Zwart Wilbert , Bergman Andries M. 
Published: June 2021

AbstractMacrophages in the tumor microenvironment are causally linked with prostate cancer development and progression, yet little is known about their composition in neoplastic human tissue. By performing single cell transcriptomic analysis of human prostate cancer resident macrophages, three distinct populations were identified in the diseased prostate. Unexpectedly, no differences were observed between macrophages isolated from the tumorous and nontumorous portions of the prostatectomy specimens. Markers associated with canonical M1 and M2 macrophage phenotypes were identifiable, however these were not the main factors defining unique subtypes. The genes selectively associated with each macrophage cluster were used to develop a gene signature which was highly associated with both recurrence-free and metastasis-free survival. These results highlight the relevance of tissue-specific macrophage subtypes in the tumor microenvironment for prostate cancer progression and demonstrates the utility of profiling single-cell transcriptomics in human tumor samples as a strategy to design gene classifiers for patient prognostication.Implications:The specific macrophage subtypes present in a diseased human prostate have prognostic value, suggesting that the relative proportions of these populations are related to patient outcome. Understanding the relative contributions of these subtypes will not only inform patient prognostication, but will enable personalized immunotherapeutic strategies to increase beneficial populations or reduce detrimental populations.
Clinical Characteristics and Predictors of In-Hospital Mortality in Patients With Cardiogenic Shock: Results From the RESCUE Registry
Authors: Yang Jeong Hoon , Choi Ki Hong , Ko Young-Guk , Ahn Chul-Min , Yu Cheol Woong , Chun Woo Jung , Jang Woo Jin , Kim Hyun-Joong , Kim Bum Sung , Bae Jang-Whan , Lee Sang Yeub , Kwon Sung Uk , Lee Hyun-Jong , Lee Wang Soo , Jeong Jin-Ok , Park Sang-Don , Lim Seong-Hoon , Cho Sungsoo , Park Taek Kyu , Lee Joo Myung , Song Young Bin , Hahn Joo-Yong , Choi Seung-Hyuk , Gwon Hyeon-Cheol 
Published: June 2021

Background:
In the current era of mechanical circulatory support, limited data are available on prognosis of cardiogenic shock (CS) caused by various diseases. We investigated the characteristics and predictors of in-hospital mortality in Korean patients with CS.

Methods:
The RESCUE study (Retrospective and Prospective Observational Study to Investigate Clinical Outcomes and Efficacy of Left Ventricular Assist Device for Korean Patients With CS) is a multicenter, retrospective, and prospective registry of patients that presented with CS. Between January 2014 and December 2018, 1247 patients with CS were enrolled from 12 major centers in Korea. The primary outcome was in-hospital mortality.

Results:

In-hospital mortality rate was 33.6%. The main causes of shock were ischemic heart disease (80.7%), dilated cardiomyopathy (6.1%), myocarditis (3.2%), and nonischemic ventricular arrhythmia (2.5%). Vasopressors were used in 1081 patients (86.7%). The most frequently used vasopressor was dopamine (63.4%) followed by norepinephrine (57.3%). An intraaortic balloon pump was used in 314 patients (25.2%) and extracorporeal membrane oxygenator in 496 patients (39.8%). In multivariable analysis, age ≥70years (odds ratio [OR], 2.73 [95% CI, 1.89–3.94],
P
<0.001), body mass index <25 kg/m
2
(OR, 1.52 [95% CI, 1.08–2.16],
P
=0.017), cardiac arrest at presentation (OR, 2.16 [95% CI, 1.44–3.23],
P
<0.001), vasoactive-inotrope score >80 (OR, 3.55 [95% CI, 2.54–4.95],
P
<0.001), requiring continuous renal replacement therapy (OR, 4.14 [95% CI, 2.88–5.95],
P
<0.001), mechanical ventilator (OR, 3.17 [95% CI, 2.16–4.63],
P
<0.001), intraaortic balloon pump (OR, 1.55 [95% CI, 1.07–2.24],
P
=0.020), and extracorporeal membrane oxygenator (OR, 1.85 [95% CI, 1.25–2.76],
P
=0.002) were independent predictors for in-hospital mortality.

Conclusions:
The in-hospital mortality of patients with CS remains high despite the high utilization of mechanical circulatory support. Age, low body mass index, cardiac arrest at presentation, amount of vasopressor, and advanced organ failure requiring various support devices were poor prognostic factors for in-hospital mortality.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02985008.
Potential Role of Natriuretic Response to Furosemide Stress Test During Acute Heart Failure
Authors: Caravaca Pérez Pedro , Nuche Jorge , Morán Fernández Laura , Lora David , Blázquez-Bermejo Zorba , López-Azor Juan Carlos , de Juan Bagudá Javier , García-Cosío Carmena María Dolores , Escribano Subías Pilar , Salguero-Bodes Rafael , Arribas Ynsaurriaga Fernando , Delgado Juan F. 
Published: June 2021

Background:
Poor natriuresis has been associated with a poorer response to diuretic treatment and worse prognosis in acute heart failure. Recommendations on how and when to measure urinary sodium (UNa) are lacking. We aim to evaluate UNa quantification after a furosemide stress test (FST) capacity to predict appropriate decongestion during acute heart failure hospitalization.

Methods:
Patients underwent an FST on day-1 of admission, and UNa was measured 2 hours after, dividing patients into low or high UNa based on the sample median value. A semiquantitative composite congestive score (CCS; 0–9) and NT pro-BNP (N-terminal pro-B-type natriuretic peptide) quantification were assessed before the FST and at day 5 after the FST.

Results:

Median UNa after FST in the 65 patients included was 113 (97–122) mmol/L. At day 5, a lower proportion of patients with a low UNa reached a 30% decrease in NT-proBNP levels (21 [66%] for low UNa versus 31 [94%] for high UNa;
P
=0.005) and an appropriate grade of decongestion (CCS<3) (20 [62%] for low UNa versus 32 [97%] for high UNa;
P
<0.001). A UNa>83 mmol/L 2 hours after FST had a 96% sensitivity to predict an NT-proBNP reduction ≥30% and 95% to predict a CCS<3 at day 5. Low UNa patients presented a lower cumulative diuresis and weight loss and presented more often with prolonged hospitalization, worsening heart failure, and readmission because of acute heart failure or death at 6 months.

Conclusions:
Low natriuresis after an FST identified patients at a higher risk of an inadequate diuretic response and an inappropriate decongestion. FST-guided diuretic treatment might help to improve decongestion, shorten hospitalizations, and to reduce adverse outcomes.
Deep Learning to Predict Cardiac Magnetic Resonance–Derived Left Ventricular Mass and Hypertrophy From 12-Lead ECGs
Authors: Khurshid Shaan , Friedman Samuel , Pirruccello James P. , Di Achille Paolo , Diamant Nathaniel , Anderson Christopher D. , Ellinor Patrick T. , Batra Puneet , Ho Jennifer E. , Philippakis Anthony A. , Lubitz Steven A. 
Published: June 2021

Background:
Classical methods for detecting left ventricular (LV) hypertrophy (LVH) using 12-lead ECGs are insensitive. Deep learning models using ECG to infer cardiac magnetic resonance (CMR)-derived LV mass may improve LVH detection.

Methods:
Within 32 239 individuals of the UK Biobank prospective cohort who underwent CMR and 12-lead ECG, we trained a convolutional neural network to predict CMR-derived LV mass using 12-lead ECGs (left ventricular mass-artificial intelligence [LVM-AI]). In independent test sets (UK Biobank [n=4903] and Mass General Brigham [MGB, n=1371]), we assessed correlation between LVM-AI predicted and CMR-derived LV mass and compared LVH discrimination using LVM-AI versus traditional ECG-based rules (ie, Sokolow-Lyon, Cornell, lead aVL rule, or any ECG rule). In the UK Biobank and an ambulatory MGB cohort (MGB outcomes, n=28 612), we assessed associations between LVM-AI predicted LVH and incident cardiovascular outcomes using age- and sex-adjusted Cox regression.

Results:
LVM-AI predicted LV mass correlated with CMR-derived LV mass in both test sets, although correlation was greater in the UK Biobank (r=0.79) versus MGB (r=0.60, P<0.001 for both). When compared with any ECG rule, LVM-AI demonstrated similar LVH discrimination in the UK Biobank (LVM-AI c-statistic 0.653 [95% CI, 0.608 -0.698] versus any ECG rule c-statistic 0.618 [95% CI, 0.574 -0.663], P=0.11) and superior discrimination in MGB (0.621; 95% CI, 0.592 -0.649 versus 0.588; 95% CI, 0.564 -0.611, P=0.02). LVM-AI-predicted LVH was associated with incident atrial fibrillation, myocardial infarction, heart failure, and ventricular arrhythmias.

Conclusions:
Deep learning-inferred LV mass estimates from 12-lead ECGs correlate with CMR-derived LV mass, associate with incident cardiovascular disease, and may improve LVH discrimination compared to traditional ECG rules.
Deep Learning–Based Automated Echocardiographic Quantification of Left Ventricular Ejection Fraction: A Point-of-Care Solution
Authors: Asch Federico M. , Mor-Avi Victor , Rubenson David , Goldstein Steven , Saric Muhamed , Mikati Issam , Surette Samuel , Chaudhry Ali , Poilvert Nicolas , Hong Ha , Horowitz Russ , Park Daniel , Diaz-Gomez Jose L. , Boesch Brandon , Nikravan Sara , Liu Rachel B. , Philips Carolyn , Thomas James D. , Martin Randolph P. , Lang Roberto M. 
Published: June 2021

Background:
We have recently tested an automated machine-learning algorithm that quantifies left ventricular (LV) ejection fraction (EF) from guidelines-recommended apical views. However, in the point-of-care (POC) setting, apical 2-chamber views are often difficult to obtain, limiting the usefulness of this approach. Since most POC physicians often rely on visual assessment of apical 4-chamber and parasternal long-axis views, our algorithm was adapted to use either one of these 3 views or any combination. This study aimed to (1) test the accuracy of these automated estimates; (2) determine whether they could be used to accurately classify LV function.

Methods:
Reference EF was obtained using conventional biplane measurements by experienced echocardiographers. In protocol 1, we used echocardiographic images from 166 clinical examinations. Both automated and reference EF values were used to categorize LV function as hyperdynamic (EF>73%), normal (53%–73%), mildly-to-moderately (30%–52%), or severely reduced (<30%). Additionally, LV function was visually estimated for each view by 10 experienced physicians. Accuracy of the detection of reduced LV function (EF<53%) by the automated classification and physicians’ interpretation was assessed against the reference classification. In protocol 2, we tested the new machine-learning algorithm in the POC setting on images acquired by nurses using a portable imaging system.

Results:
Protocol 1: the agreement with the reference EF values was good (intraclass correlation, 0.86–0.95), with biases <2%. Machine-learning classification of LV function showed similar accuracy to that by physicians in most views, with only 10% to 15% cases where it was less accurate. Protocol 2: the agreement with the reference values was excellent (intraclass correlation=0.84) with a minimal bias of 2.5±6.4%.

Conclusions:
The new machine-learning algorithm allows accurate automated evaluation of LV function from echocardiographic views commonly used in the POC setting. This approach will enable more POC personnel to accurately assess LV function.
Propagation of Topographic Rossby Waves in the Deep Basin of the South China Sea Based on Abyssal Current Observations
Authors: Zheng Hua , Zhu Xiao-Hua , Zhang Chuanzheng , Zhao Ruixiang , Zhu Ze-Nan , Liu Zhao-Jun 
Published: June 2021

AbstractTopographic Rossby waves (TRWs) are oscillations generated on sloping topography when water columns travel across isobaths under potential vorticity conservation. From our large-scale observations from 2016 to 2019, near-65-day TRWs were first observed in the deep basin of the South China Sea (SCS). The TRWs propagated westward with a larger wavelength (235 km) and phase speed (3.6 km day−1) in the north of the array and a smaller wavelength (80 km) and phase speed (1.2 km day−1) toward the southwest of the array. The ray-tracing model was used to identify the energy source and propagation features of the TRWs. The paths of the near-65-day TRWs mainly followed the isobaths with a slightly downslope propagation. The possible energy source of the TRWs was the variance of surface eddies southwest of Taiwan. The near-65-day energy propagated from the southwest of Taiwan to the northeast and southwest of the array over ~100–120 and ~105 days, respectively, corresponding to a group velocity of 4.2–5.0 and 10.5 km day−1, respectively. This suggests that TRWs play an important role in deep-ocean dynamics and deep current variation, and upper-ocean variance may adjust the intraseasonal variability in the deep SCS.
Impact of Frailty on Clinical Outcomes and Hospitalization Costs Following Elective Colectomy
Authors: Hadaya Joseph , Mandelbaum Ava , Sanaiha Yas , Benharash Peyman 
Published: June 2021

Background Frailty has been increasingly recognized as a risk factor for inferior surgical outcomes and greater resource use. The present study evaluated the impact of a coding-based frailty tool on outcomes of elective colectomy in a national cohort. Study Design Adults undergoing elective colectomy were identified in the 2016-17 Nationwide Readmissions Database. Frailty was defined using the Johns Hopkins 10-domain coding-based binary tool. Generalized linear models were used to examine the association of frailty with in-hospital mortality, nonhome discharge, hospitalization duration (LOS), and inflation-adjusted costs. Kaplan-Meier survival analysis and log-rank test was used to compare readmissions up to 1-year. Results Of 133 175 patients, 10.6% were considered frail. The most common resections were sigmoid (43.9%) and right (34.7%) while total colectomy was least common (2.8%). After adjustment, frailty was associated with greater odds of mortality (3.2, 95% CI 2.8-3.8) and nonhome discharge (6.0, 95% CI 5.5-6.4) as well as a $13,400-increment (95% CI 12,400-14,400) in costs and 4.4-day (95% CI 4.1-4.6) increase in LOS. Nonelective readmissions at 30 days were greater in frail than non-frail groups (14.7% vs. 10.4%, P < .001). Conclusion Frailty is associated with inferior clinical outcomes and increased resource use following elective colectomy. Inclusion of frailty in risk models may facilitate risk stratification and shared decision-making.
Non-Selective Thoracic Computed Tomography in Trauma Patients Results in Injury Severity Score Inflation
Authors: Alaniz Leonardo , Muttalib Omaer , Hoyos Juan , Figueroa Cesar , Barrios Cristobal 
Published: June 2021

Introduction Extensive research relying on Injury Severity Scores (ISS) reports a mortality benefit from routine non-selective thoracic CTs (an integral part of pan-computed tomography (pan-CT)s). Recent research suggests this mortality benefit may be artifact. We hypothesized that the use of pan-CTs inflates ISS categorization in patients, artificially affecting admission rates and apparent mortality benefit. Methods Eight hundred and eleven patients were identified with an ISS >15 with significant findings in the chest area. Patient charts were reviewed and scores were adjusted to exclude only occult injuries that did not affect treatment plan. Pearson chi-square tests and multivariable logistic regression were used to compare adjusted cases vs non-adjusted cases. Results After adjusting for inflation, 388 (47.8%) patients remained in the same ISS category, 378 (46.6%) were reclassified into 1 lower ISS category, and 45 (5.6%) patients were reclassified into 2 lower ISS categories. Patients reclassified by 1 category had a lower rate of mortality ( P < 0.001), lower median total hospital LOS ( P < .001), ICU days ( P < .001), and ventilator days ( P = 0.008), compared to those that remained in the same ISS category. Conclusion Injury Severity Score inflation artificially increases survival rate, perpetuating the increased use of pan-CTs. This artifact has been propagated by outdated mortality prediction calculation methods. Thus, prospective evaluations of algorithms for more selective CT scanning are warranted.
Increased Mortality in Underinsured Penetrating Trauma Patients
Authors: Alaniz Leonardo , Billimek John , Figueroa Cesar , Nahmias Jeffry T. , Barrios Cristobal 
Published: June 2021

Introduction It remains unclear whether an increased mortality risk in uninsured patients exists across Injury Severity Score (ISS) classifications. We hypothesized that penetrating trauma self-pay patients would have a similarly increased mortality risk across all ISS categories. Methods The National Trauma Data Bank (2013-2015) was queried for patients presenting with penetrating firearm, explosive, or stab wound injuries. 115 651 patients were identified and a stratified multivariable logistic regression model was used. Results In the >15 ISS group, self-pay patients had a lower median total hospital Length of Stay (LOS) (3 vs 8, P < .001), lower median Intensive Care Unit LOS (1 vs 3, P < .001), and lower median ventilator days (0 vs 1, P < .001). Self-pay patients had an increased risk for mortality compared to patients with private insurance in both the ≤15 ISS group (OR 2.68, P < .001) and >15 ISS group (OR 1.56, P < .001). Conclusion Uninsured patients have an increased mortality risk in both low and high ISS groups. A higher mortality risk among uninsured patients in the high ISS group can be explained by decreased resource availability and lower ICU days and ventilator time. However, more studies are needed to determine why there is an even greater mortality risk among uninsured patients with mild ISS.
A Smartphone Application for Teamwork and Communication in Trauma: Pilot Evaluation “in the Wild”
Authors: Catchpole Ken , Privette Alicia , Roberts Laura , Alfred Myrtede , Carter Brittan , Woltz Erick , Wilson Dulaney , Crookes Bruce 
Published: June 2021

Objective To evaluate the potential for a smartphone application to improve trauma care through shared and timely access to patient and contextual information. Background Disruptions along the trauma pathway that arise from communication, coordination, and handoffs problems can delay progress through initial care, imaging diagnosis, and surgery to intensive care unit (ICU) disposition. Implementing carefully designed and evaluated information distribution and communication technologies may afford opportunities to improve clinical performance. Methods This was a pilot evaluation “in the wild” using a before/after design, 3 month, and pre- post-intervention data collection. Use statistics, usability assessment, and direct observation of trauma care were used to evaluate the app. Ease of use and utility were assessed using the technology acceptance model (TAM) and system usability scale (SUS). Direct observation deployed measures of flow disruptions (defined as “deviations from the natural progression of an procedure”), teamwork scores (T-NOTECHS), and treatment times (total time in emergency department [ED]). Results The app was used in 367 (87%) traumas during the trial period. Usability was generally acceptable, with higher scores found by operating room (OR), ICU, and neuro and orthopedic users. Despite positive trends, no significant effects on flow disruptions, teamwork scores, or treatment times were observed. Conclusions Pilot trials of a clinician-centered smartphone app to improve teamwork and communication demonstrate potential value for the safety and efficiency of trauma care delivery as well as benefits and challenges of “in-the-wild” evaluation.