bluuebunny/crossref_metadata_2025_split huggingface dataset:
Late graft failure of pig‐to‐rhesus renal xenografts has features of glomerulopathy and recipients have anti‐swine leukocyte antigen class I and class II antibodies
Authors: Ladowski Joseph M. , Tector Matt , Martens Gregory , Wang Zheng Yu , Burlak Chris , Reyes Luz , Estrada Jose , Adams Andrew , Tector A. Joseph 
Published: May 2024

AbstractProlonged survival in preclinical renal xenotransplantation demonstrates that early antibody mediated rejection (AMR) can be overcome. It is now critical to evaluate and understand the pathobiology of late graft failure and devise new means to improve post xenograft outcomes. In renal allotransplantation the most common cause of late renal graft failure is transplant glomerulopathy—largely due to anti‐donor MHC antibodies, particularly anti‐HLA DQ antibodies. We evaluated the pig renal xenograft pathology of four long‐surviving (>300 days) rhesus monkeys. We also evaluated the terminal serum for the presence of anti‐SLA class I and specifically anti‐SLA DQ antibodies. All four recipients had transplant glomerulopathy and expressed anti‐SLA DQ antibodies. In one recipient tested for anti‐SLA I antibodies, the recipient had antibodies specifically reacting with two of three SLA I alleles tested. These results suggest that similar to allotransplantation, anti‐MHC antibodies, particularly anti‐SLA DQ, may be a barrier to improved long‐term xenograft outcomes.
Improving NLO QCD event generators with high-energy EW corrections
Authors: Pagani Davide , Vitos Timea , Zaro Marco 
Published: May 2024

AbstractIn this work we present a new method for the combination of electroweak (EW) corrections at high energies, the so-called EW Sudakov logarithms (EWSL), and next-to-leading-order QCD predictions matched to parton-shower simulations (NLO+PS). Our approach is based on a reweighting procedure of NLO+PS events. In particular, both events with and without an extra hard emission from matrix elements are consistently reweighted via the inclusion of the corresponding EWSL contribution. We describe the technical details and the implementation in the MadGraph5_aMC@NLO framework. Via a completely automated procedure, events at this level of accuracy can be obtained for a vast class of hadroproduction processes. As a byproduct we provide results for phenomenologically relevant physical distributions from top-quark pair and Higgs boson associated production ($$t {\bar{t}} H$$

t

t

¯

H

) and from the associated production of three Z gauge bosons (ZZZ).
Cardiovascular Risk Estimation Is Suboptimal in People With HIV
Authors: Triant Virginia A. , Lyass Asya , Hurley Leo B. , Borowsky Leila H. , Ehrbar Rachel Q. , He Wei , Cheng David , Lo Janet , Klein Daniel B. , Meigs James B. , Grinspoon Steven K. , Plutzky Jorge , Silverberg Michael J. , LaValley Michael , Massaro Joseph M. , D'Agostino Ralph B. 
Published: May 2024

Background
Established cardiovascular disease (CVD) risk prediction functions may not accurately predict CVD risk in people with HIV. We assessed the performance of 3 CVD risk prediction functions in 2 HIV cohorts.

Methods and Results
CVD risk scores were calculated in the Mass General Brigham and Kaiser Permanente Northern California HIV cohorts, using the American College of Cardiology/American Heart Association atherosclerotic CVD function, the FHS (Framingham Heart Study) hard coronary heart disease function and the Framingham Heart Study hard CVD function. Outcomes were myocardial infarction or coronary death for FHS hard coronary heart disease function; and myocardial infarction, stroke, or coronary death for American College of Cardiology/American Heart Association and FHS hard CVD function. We calculated regression coefficients and assessed discrimination and calibration by sex; predicted to observed risk of outcome was also compared. In the combined cohort of 9412, 158 (1.7%) had a coronary heart disease event, and 309 (3.3%) had a CVD event. Among women, CVD risk was generally underestimated by all 3 risk functions. Among men, CVD risk was underestimated by the American College of Cardiology/American Heart Association and FHS hard CVD function, but overestimated by the FHS hard coronary heart disease function. Calibration was poor for women using the FHS hard CVD function and for men using all functions. Discrimination in all functions was good for women (c‐statistics ranging from 0.78 to 0.90) and moderate for men (c‐statistics ranging from 0.71 to 0.72).

Conclusions
Established CVD risk prediction functions generally underestimate risk in people with HIV. Differences in model performance by sex underscore the need for both HIV‐specific and sex‐specific functions. Development of CVD risk prediction models tailored to HIV will enhance care for aging people with HIV.
Optimal Timing for Resumption of Anticoagulation After Intracranial Hemorrhage in Patients With Mechanical Heart Valves
Authors: Barra Megan E. , Forman Rachel , Long‐Fazio Bianca , Merkler Alexander E. , Gurol M. E. , Izzy Saef , Sharma Richa 
Published: May 2024

Background
Anticoagulation in patients with intracranial hemorrhage (ICH) and mechanical heart valves is often held for risk of ICH expansion; however, there exists a competing risk of acute ischemic stroke (AIS). Optimal timing to resume anticoagulation remains uncertain.

Methods and Results

We retrospectively studied patients with ICH and mechanical heart valves from 2000 to 2018. The primary outcome was a composite end point of symptomatic hematoma expansion or new ICH, AIS, and intracardiac thrombus up to 30 days post‐ICH. The exposure was timing of reinitiation of anticoagulation classified as early (resumed up to 7 days after ICH), late (≥7 and up to 30 days after ICH), and never if not resumed or resumed after 30 days post‐ICH. We included 184 patients with ICH and mechanical heart valves (65 anticoagulated early, 100 late, 19 not resumed by day 30 post‐ICH). Twelve patients had AIS, 16 new ICH, and 6 intracardiac thromboses. The mean time from ICH to anticoagulation was 12.7 days. Composite outcomes occurred in 12 patients resumed early (18.5%), 14 resumed late (14.0%), and 4 never resumed (21.1%). There was no increased hazard of the composite outcome (hazard ratio [HR], 1.1 [95% CI, 0.2–6.0]), AIS, or worsening or new ICH among patients resumed early versus late. There was no difference in the composite among patients never resumed versus resumed. Patients who never resumed anticoagulation had significantly more severe ICH (median Glasgow Coma Scale: 10.6, 13.9, and 13.9 among those who resumed never, early, and late, respectively;
P
=0.0001), higher in‐hospital mortality (56.5%, 0%, and 0%, respectively;
P
<0.0001), and an elevated 30‐day AIS risk (HR, 15.9 [95% CI, 1.9–129.7],
P
=0.0098).

Conclusions
In this study of patients with ICH and mechanical heart valves, there was no difference in 30‐day thrombotic and hemorrhagic brain‐related outcomes when anticoagulation was resumed within 7 versus 7 to 30 days after ICH. Withholding anticoagulation >30 days was associated with severe baseline ICH, higher in‐hospital case fatality, and elevated AIS risk.
Assessing Glycosylated Hemoglobin Thresholds for Development of Cardiovascular Disease by Racial and Ethnic Groups
Authors: Low Christopher G. , Merchant Maqdooda , Hung Yun‐Yi , Liu Yu Hsin , Vu Joseph , Pursnani Seema 
Published: May 2024

Background
Diabetes is the strongest risk factor for cardiovascular disease, and although glycosylated hemoglobin (HbA1c) levels are known to vary by race, no racial and ethnic–specific diagnostic thresholds exist for diabetes in prediction of cardiovascular disease events. The purpose of this study is to determine whether HbA1c thresholds for predicting major adverse cardiovascular events (MACEs) differ among racial and ethnic groups.

Methods and Results

This is a retrospective cohort study of Kaiser Permanente Northern California adult members (n=309 636) with no history of cardiovascular disease who had HbA1c values and race and ethnicity data available between 2014 and 2019. Multivariable logistic regression was used to evaluate the odds of MACEs by the following racial and ethnic groups: Filipino, South Asian, East Asian, Black, White, and Hispanic. A Youden index was used to calculate HbA1c thresholds for MACE prediction by each racial and ethnic group, stratified by sex. Among studied racial and ethnic groups, South Asian race was associated with the greatest odds of MACEs (1.641 [95% CI, 1.456–1.843];
P
<0.0001). HbA1c was a positive predictor for MACEs, with an odds ratio of 1.024 (95% CI, 1.022–1.025) for each 0.1% increment increase in HbA1c. HbA1c values varied between 6.0% and 7.6% in MACE prediction by race and ethnicity and sex. White individuals, South Asian individuals, East Asian women, and Black men had HbA1c thresholds for MACE prediction in the prediabetic range, between 6.0% and 6.2%. Black women, Hispanic men, and East Asian men had HbA1c thresholds of 6.2% to 6.6%, less than the typical threshold of 7.0% that is used as a treatment goal.

Conclusions
Findings suggest that the use of race and ethnic– and sex‐specific HbA1c thresholds may need to be considered in treatment goals and cardiovascular disease risk estimation.
Mortality Benefits of Cardiac Rehabilitation in Coronary Artery Disease Are Mediated by Comprehensive Risk Factor Modification: A Retrospective Cohort Study
Authors: Rouleau Codie R. , Chirico Daniele , Wilton Stephen B. , MacDonald Matthew K. , Tao Tianqi , Arena Ross , Campbell Tavis , Aggarwal Sandeep 
Published: May 2024

Background
Cardiac rehabilitation (CR) is a multicomponent intervention to reduce adverse outcomes from coronary artery disease, but its mechanisms are not fully understood. The aims of this study were to examine the impact of CR on survival and cardiovascular risk factors, and to determine potential mediators between CR attendance and reduced mortality.

Methods and Results

A retrospective mediation analysis was conducted among 11 196 patients referred to a 12‐week CR program following an acute coronary syndrome event between 2009 and 2019. A panel of cardiovascular risk factors was assessed at a CR intake visit and repeated on CR completion. All‐cause and cardiovascular mortality were ascertained via health care administrative data sets at mean 4.2‐year follow‐up (SD, 2.81 years). CR completion was associated with reduced all‐cause (adjusted hazard ratio [HR], 0.67 [95% CI, 0.54–0.83]) and cardiovascular (adjusted HR, 0.57 [95% CI, 0.40–0.81]) mortality, as well as improved cardiorespiratory fitness, lipid profile, body composition, psychological distress, and smoking rates (
P
<0.001). CR attendance had an indirect effect on all‐cause mortality via improved cardiorespiratory fitness (
ab
=−0.006 [95% CI, −0.008 to −0.003]) and via low‐density lipoprotein cholesterol (
ab
=−0.002 [95% CI, −0.003 to −0.0003]) and had an indirect effect on cardiovascular mortality via cardiorespiratory fitness (
ab
=−0.007 [95% CI, −0.012 to −0.003]).

Conclusions
Cardiorespiratory fitness and lipid control partly explain the mortality benefits of CR and represent important secondary prevention targets.
Comparison of Contemporary Treatment Strategies in Patients With Cardiogenic Shock Due to Severe Aortic Stenosis
Authors: Nair Raunak M. , Chawla Sanchit , Abdelghaffar Bahaa , Alkhalaieh Feras , Bansal Agam , Puri Rishi , Yun James , Krishnaswamy Amar , Kapadia Samir , Menon Venu , Reed Grant W. 
Published: May 2024

Background
The aims of this study were to understand the incidence and outcomes of patients with cardiogenic shock (CS) due to severe aortic stenosis (AS), and the impact of conventional treatment strategies in this population.

Methods and Results

All patients admitted to the Cleveland Clinic cardiac intensive care unit between January 1, 2010 and December 31, 2021 with CS were retrospectively identified and categorized into those with CS in the setting of severe AS versus CS without AS. The impact of various treatment strategies on mortality was further assessed. We identified 2754 patients with CS during the study period, of whom 216 patients (8%) had CS in the setting of severe AS. Medical management was associated with the highest 30‐day mortality when compared with either balloon aortic valve replacement or aortic valve replacement (surgical or transcatheter aortic valve replacement) (hazard ratio, 3.69 [95% CI, 2.04–6.66];
P
<0.0001). Among patients who received transcatheter therapy, 30‐day mortality was significantly higher in patients who received balloon aortic valvuloplasty versus transcatheter aortic valve replacement (26% versus 4%,
P
=0.02). Both surgical and transcatheter aortic valve replacement had considerably lower mortality than medical management and balloon aortic valvuloplasty at 30 days and 1 year (
P
<0.05 for both comparisons).

Conclusions
CS due to severe AS is associated with high in‐hospital and 30‐day mortality, worse compared with those with CS without AS. In suitable patients, urgent surgical aortic valvuloplasty or transcatheter aortic valve replacement is associated with favorable short‐ and long‐term outcomes. Although balloon aortic valvuloplasty may be used to temporize patients with CS in the setting of severe AS, mortality is ≈50% if not followed by definitive aortic valve replacement within 90 days.
Trends in Dual Antiplatelet Therapy of Aspirin and Clopidogrel and Outcomes in Ischemic Stroke Patients Noneligible for POINT/CHANCE Trial Treatment
Authors: Kim Joon‐Tae , Lee Ji Sung , Kim Hyunsoo , Kim Beom Joon , Lee Keon‐Joo , Park Jong‐Moo , Kang Kyusik , Lee Soo Joo , Kim Jae Guk , Cha Jae‐Kwan , Kim Dae‐Hyun , Park Tai Hwan , Lee Kyungbok , Lee Jun , Hong Keun‐Sik , Cho Yong‐Jin , Park Hong‐Kyun , Lee Byung‐Chul , Yu Kyung‐Ho , Oh Mi Sun , Kim Dong‐Eog , Choi Jay Chol , Kwon Jee‐Hyun , Kim Wook‐Joo , Shin Dong‐Ick , Yum Kyu Sun , Sohn Sung Il , Hong Jeong‐Ho , Lee Sang‐Hwa , Park Man‐Seok , Ryu Wi‐Sun , Park Kwang‐Yeol , Lee Juneyoung , Saver Jeffrey L. , Bae Hee‐Joon 
Published: May 2024

Background
Recent clinical trials established the benefit of dual antiplatelet therapy with aspirin and clopidogrel (DAPT‐AC) in early‐presenting patients with minor ischemic stroke. However, the impact of these trials over time on the use and outcomes of DAPT‐AC among the patients with nonminor or late‐presenting stroke who do not meet the eligibility criteria of these trials has not been delineated.

Methods and Results

In a multicenter stroke registry, this study examined yearly changes from April 2008 to August 2022 in DAPT‐AC use for stroke patients ineligible for CHANCE/POINT (Clopidogrel in High‐Risk Patients with Acute Nondisabling Cerebrovascular Events/Platelet‐Oriented Inhibition in New TIA and Minor Ischemic Stroke) clinical trials due to National Institutes of Health Stroke Scale >4 or late arrival beyond 24 hours of onset. A total of 32 118 patients (age, 68.1±13.1 years; male, 58.5%) with National Institutes of Health Stroke Scale of 4 (interquartile range, 1–7) were analyzed. In 2008, DAPT‐AC was used in 33.0%, other antiplatelets in 62.7%, and no antiplatelet in 4.3%. The frequency of DAPT‐AC was relatively unchanged through 2013, when the CHANCE trial was published, and then increased steadily, reaching 78% in 2022, while other antiplatelets decreased to 17.8% in 2022 (
P
trend
<0.001). From 2011 to 2022, clinical outcomes nonsignificantly improved, with an average relative risk reduction of 2%/y for the composite of stroke, myocardial infarction, and all‐cause mortality, both among patients treated with DAPT‐AC and patients treated with other antiplatelets.

Conclusions
Use of DAPT‐AC in stroke patients with stroke ineligible for recent DAPT clinical trials increased markedly and steadily after CHANCE publication in 2013, reaching deployment in nearly 4 of every 5 patients by 2022. The secondary prevention in patients with ischemic stroke seems to be gradually improving, possibly due to the enhancement of risk factor control.
Association of Lipoprotein (a) and Standard Modifiable Cardiovascular Risk Factors With Incident Myocardial Infarction: The Mass General Brigham Lp(a) Registry
Authors: Shiyovich Arthur , Berman Adam N. , Besser Stephanie A. , Biery David W. , Kaur Gurleen , Divakaran Sanjay , Singh Avinainder , Huck Daniel M. , Weber Brittany , Plutzky Jorge , Di Carli Marcelo F. , Nasir Khurram , Cannon Christopher , Januzzi James L. , Bhatt Deepak L. , Blankstein Ron 
Published: May 2024

Background
Lipoprotein (a) [Lp(a)] is a robust predictor of coronary heart disease outcomes, with targeted therapies currently under investigation. We aimed to evaluate the association of high Lp(a) with standard modifiable risk factors (SMuRFs) for incident first acute myocardial infarction (AMI).

Methods and Results

This retrospective study used the Mass General Brigham Lp(a) Registry, which included patients aged ≥18 years with an Lp(a) measurement between 2000 and 2019. Exclusion criteria were severe kidney dysfunction, malignant neoplasm, and prior known atherosclerotic cardiovascular disease. Diabetes, dyslipidemia, hypertension, and smoking were considered SMuRFs. High Lp(a) was defined as >90th percentile, and low Lp(a) was defined as <50th percentile. The primary outcome was fatal or nonfatal AMI. A combination of natural language processing algorithms,
International Classification of Diseases
(
ICD
) codes, and laboratory data was used to identify the outcome and covariates. A total of 6238 patients met the eligibility criteria. The median age was 54 (interquartile range, 43–65) years, and 45% were women. Overall, 23.7% had no SMuRFs, and 17.8% had ≥3 SMuRFs. Over a median follow‐up of 8.8 (interquartile range, 4.2–12.8) years, the incidence of AMI increased gradually, with higher number of SMuRFs among patients with high (log‐rank
P
=0.031) and low Lp(a) (log‐rank
P
<0.001). Across all SMuRF subgroups, the incidence of AMI was significantly higher for patients with high Lp(a) versus low Lp(a). The risk of high Lp(a) was similar to having 2 SMuRFs. Following adjustment for confounders and number of SMuRFs, high Lp(a) remained significantly associated with the primary outcome (hazard ratio, 2.9 [95% CI, 2.0–4.3];
P
<0.001).

Conclusions
Among patients with no prior atherosclerotic cardiovascular disease, high Lp(a) is associated with significantly higher risk for first AMI regardless of the number of SMuRFs.
Trends in Survival After First Myocardial Infarction in People With Diabetes
Authors: Glynn Linn , Lind Marcus , Andersson Tomas , Eliasson Björn , Hofmann Robin , Nyström Thomas 
Published: May 2024

Background
The aim of this study was to investigate temporal trends in survival and subsequent cardiovascular events in a nationwide myocardial infarction population with and without diabetes.

Methods and Results
Between 2006 and 2020, we identified 2527 individuals with type 1 diabetes, 48 321 individuals with type 2 diabetes and 243 170 individuals without diabetes with first myocardial infarction in national health care registries. Outcomes were trends in all‐cause death after 30 and 365 days, cardiovascular death and major adverse cardiovascular events (ie, nonfatal stroke, nonfatal myocardial infarction, cardiovascular death, and heart failure hospitalization). Pseudo‐observations were used to estimate the mortality risk, with 95% CIs, using linear regression, adjusted for age and sex. Individuals with type 1 diabetes were younger (62±12.2 years) and more often women (43.6%) compared with individuals with type 2 diabetes (75±10.8 years; women, 38.1%), and individuals without diabetes (73±13.2 years; women, 38.4%). Early death decreased in people without diabetes from 23.1% to 17.5%, (annual change −0.48% [95% CI, −0.52% to −0.44%]) and in people with type 2 diabetes from 22.6% to 19.3% (annual change, −0.33% [95% CI, −0.43% to −0.24%]), with no such significant trend in people with type 1 diabetes from 23.8% to 21.7% (annual change, −0.18% [95% CI, −0.53% to 0.17%]). Similar trends were observed with regard to 1‐year death, cardiovascular death, and major adverse cardiovascular events.

Conclusions
During the past 15 years, the trend in survival and major adverse cardiovascular events in people with first myocardial infarction without diabetes and with type 2 diabetes have improved significantly. In contrast, a similar improvement was not seen in people with type 1 diabetes.
Differential Effect of Aortic Valve Replacement for Severe Aortic Stenosis on Hyperemic and Resting Epicardial Coronary Pressure Indices
Authors: Minten Lennert , Bennett Johan , Otsuki Hisao , Takahashi Kuniaki , Fearon William F. , Dubois Christophe 
Published: May 2024

Background
Coronary pressure indices to assess coronary artery disease are currently underused in patients with aortic stenosis due to many potential physiological effects that might hinder their interpretation. Studies with varying sample sizes have provided us with conflicting results on the effect of transcatheter aortic valve replacement (TAVR) on these indices. The aim of this meta‐analysis was to study immediate and long‐term effects of TAVR on fractional flow reserve (FFR) and nonhyperemic pressure ratios (NHPRs).

Methods and Results

Lesion‐specific coronary pressure data were extracted from 6 studies, resulting in 147 lesions for immediate change in FFR analysis and 105 for NHPR analysis. To investigate the long‐term changes, 93 lesions for FFR analysis and 68 for NHPR analysis were found. Lesion data were pooled and compared with paired
t
tests. Immediately after TAVR, FFR decreased significantly (−0.0130±0.0406 SD,
P
: 0.0002) while NHPR remained stable (0.0003±0.0675,
P
: 0.9675). Long‐term after TAVR, FFR decreased significantly (−0.0230±0.0747,
P
: 0.0038) while NHPR increased nonsignificantly (0.0166±0.0699,
P
: 0.0543). When only borderline NHPR lesions were considered, this increase became significant (0.0249±0.0441,
P
: 0.0015). Sensitivity analysis confirmed our results in borderline lesions.

Conclusions
TAVR resulted in small significant, but opposite, changes in FFR and NHPR. Using the standard cut‐offs in patients with severe aortic stenosis, FFR might underestimate the physiological significance of a coronary lesion while NHPRs might overestimate its significance. The described changes only play a clinically relevant role in borderline lesions. Therefore, even in patients with aortic stenosis, an overtly positive or negative physiological assessment can be trusted.