bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lipoprotein(a) is associated with a larger systemic burden of arterial calcification
Authors: Singh Sunny S , van der Toorn Janine E , Sijbrands Eric J G , de Rijke Yolanda B , Kavousi Maryam , Bos Daniel 
Published: April 2023

Abstract

Aims
Lipoprotein(a) [Lp(a)] is a genetically determined risk factor for cardiovascular disease. However, population-based evidence on the link between Lp(a) and subclinical arteriosclerosis is lacking. We assessed associations of Lp(a) concentrations with arteriosclerosis in multiple arteries.

Methods and results
From the population-based Rotterdam study, 2354 participants (mean age: 69.5 years, 52.3% women) underwent non-contrast computed tomography to assess arterial calcification as a hallmark of arteriosclerosis. We quantified the volume of coronary artery calcification (CAC), aortic arch calcification (AAC), extracranial (ECAC), and intracranial carotid artery calcification (ICAC). All participants underwent blood sampling, from which plasma Lp(a) concentrations were derived. The association of plasma Lp(a) levels was assessed with calcification volumes and with severe calcification (upper quartile of calcification volume) using sex-stratified multivariable linear and logistic regression models. Higher Lp(a) levels were associated with larger ln-transformed volumes of CAC [fully adjusted beta 95% confidence interval (CI) per 1 standard deviation (SD) in women: 0.09, 95% CI 0.04–0.14, men: 0.09, 95% CI 0.03–0.14], AAC (women: 0.06, 95% CI 0.01–0.11, men: 0.09, 95% CI 0.03–0.14), ECAC (women: 0.07, 95% CI 0.02–0.13, men: 0.08, 95% CI 0.03–0.14), and ICAC (women: 0.09, 95% CI 0.03–0.14, men: 0.05, 95% CI −0.02 to 0.11]. In the highest Lp(a) percentile, severe ICAC was most prevalent in women [fully adjusted odds ratio (OR) 2.41, 95% CI 1.25–4.63] and severe AAC in men (fully adjusted OR 3.29, 95% CI 1.67–6.49).

Conclusion
Higher Lp(a) was consistently associated with a larger calcification burden in all major arteries. The findings of this study indicate that Lp(a) is a systemic risk factor for arteriosclerosis and thus potentially an effective target for treatment. Lp(a)-reducing therapies may reduce the burden from arteriosclerotic events throughout the arterial system.

Translational perspective
In 2354 participants from the Rotterdam study, we assessed the link between Lp(a) concentrations and arterial calcifications, as proxy for arteriosclerosis, in major arteries. We found that higher Lp(a) levels were consistently associated with larger volumes of calcification in the coronary arteries, aortic arch, extracranial carotid arteries, and intracranial carotid arteries. The findings of our study indicate that Lp(a) is a systemic risk factor for arteriosclerosis, suggesting that the systemic burden of arteriosclerosis throughout the arterial system could be reduced by targeting Lp(a).
Spontaneous coronary artery dissection: the emerging role of coronary computed tomography
Authors: Pergola Valeria , Continisio Saverio , Mantovani Francesca , Motta Raffaella , Mattesi Giulia , Marrazzo Gemma , Dellino Carlo Maria , Montonati Carolina , De Conti Giorgio , Galzerano Domenico , Parato Vito Maurizio , Gimelli Alessia , Barchitta Agatella , Campana Marco , D’Andrea Antonello 
Published: April 2023

Abstract
Spontaneous coronary artery dissection (SCAD) is a cause of acute coronary syndrome and myocardial infarction, more frequent among young women. Invasive coronary angiography (ICA) is the gold standard for the diagnosis of SCAD, although the risk of propagating dissection flap is considerable. Therefore, coronary computed tomography angiography (CCTA) is an emerging alternative modality to diagnose SCAD with the advantage of being a non-invasive technique.
Clinicians should be aware of the predisposing conditions and pathophysiology to raise the pre-test probability of SCAD and select the most appropriate diagnostic tools.
In recent times, improvements in spatial and temporal resolution and the use of semi-automated software providing quantitative assessment make CCTA a valid alternative to ICA also for the follow-up. Moreover, CCTA may be helpful to screen and evaluate extra-coronary arteriopathies closely related to SCAD.
In this review, we illustrate the current and the potential role of CCTA in the diagnosis of SCAD, highlighting advantages and disadvantages of this imaging modality compared to ICA.
Benefit of icosapent ethyl on coronary physiology assessed by computed tomography angiography fractional flow reserve: EVAPORATE-FFRCT
Authors: Rabbat Mark G , Lakshmanan Suvasini , Benjamin Mina M , Doros Gheorghe , Kinninger April , Budoff Matthew J , Bhatt Deepak L 
Published: April 2023

Abstract

Aims
Icosapent ethyl (IPE) significantly reduced ischaemic events in statin-treated patients with atherosclerosis or diabetes and elevated triglycerides in REDUCE-IT, including large reductions in myocardial infarction and elective, urgent, and emergent coronary revascularization. However, the mechanisms driving this clinical benefit are not fully known. The EVAPORATE trial demonstrated that IPE significantly reduced plaque burden. No study to date has assessed the impact of IPE on coronary physiology. Fractional flow reserve (FFR) derived from coronary computed tomography angiography (CTA) data sets (FFRCT) applies computational fluid dynamics to calculate FFR values in epicardial coronary arteries. Our objective was to assess the impact of IPE on coronary physiology assessed by FFRCT using imaging data from EVAPORATE.

Methods and results
A total of 47 patients and of 507 coronary lesions at baseline, 9 months, and 18 months with coronary CTA and FFRCT were studied in a blinded core lab. The pre-specified primary endpoint was the FFRCT value in the distal coronary segment from baseline to follow-up in the most diseased vessel per patient using IPE compared with placebo. The pre-specified secondary endpoint was the change in translesional FFRCT (ΔFFRCT) across the most severe (minimum 30% diameter stenosis) coronary lesion per vessel. Baseline FFRCT was similar for IPE compared with placebo (0.83 ± 0.08 vs. 0.84 ± 0.08, P = 0.55). There was significant improvement in the primary endpoint, as IPE improved mean distal segment FFRCT at 9- and 18-month follow-up compared with placebo (0.01 ± 0.05 vs. −0.05 ± 0.09, P = 0.02, and −0.01 ± 0.09 vs. −0.09 ± 0.12, P = 0.03, respectively). ΔFFRCT in 140 coronary lesions was improved, although not statistically significant, with IPE compared with placebo (−0.06 ± 0.08 vs. −0.09 ± 0.1, P = 0.054).

Conclusion
Icosapent ethyl demonstrated significant benefits in coronary physiology compared with placebo. This early and sustained improvement in FFRCT at 9- and 18-month follow-up provides mechanistic insight into the clinical benefit observed in the REDUCE-IT trial. Furthermore, this is the first assessment of FFRCT to determine drug effect.
DOACs and rheumatic valvulopathy: always a red light?
Authors: Rochira Carla , Capodanno Davide 
Published: April 2023

Abstract
Despite the sharp decline in most high-income industrialized countries, rheumatic heart disease (RHD) continues to be highly prevalent in many rural, low- and middle-income countries. RHD most frequently involves the mitral valve, both in the form of isolated regurgitation and in the form of regurgitation associated with mitral stenosis (mitral stenosis, MS). Atrial fibrillation (AF) is a common complication of RHD that is independently associated with an increased risk of death, heart failure, and systemic thromboembolism. Few studies have focused on the issue of the best oral anticoagulation strategy for patients with RHD and AF. Randomized trials establishing the non-inferiority of new direct oral anticoagulants (DOACs) over vitamin K antagonists (VKAs) in the prevention of stroke and systemic embolism excluded AF patients with mechanical valves or with moderate-to-severe MS. Nevertheless, variable proportions of patients with other VHD types were included. Recently, the INVICTUS trial demonstrated that in patients with RHD-related AF, direct oral anticoagulant rivaroxaban is inferior to VKAs in preventing stroke, systemic embolism, myocardial infarction, or death and is similar in bleeding risk. These results confirm and reinforce the recommendations of current international guidelines supporting the use of VKAs in patients with RHD-related AF.
Treating chronic kidney disease to reduce cardiovascular risk
Authors: Cice Gennaro , Monzo Luca , Calò Leonardo 
Published: April 2023

Abstract
Chronic kidney disease (CKD) is a complex syndrome and a relevant problem of public health due to its large incidence and prevalence and to the high costs for its management. The hallmark of CKD, the progressive reduction in the glomerular filtration rate (eGFR), is strongly associated with an increase in cardiovascular events, such as fatal and non-fatal heart attack, stroke and heart failure, and mortality. Therefore, clinicians should pay any effort for preventing or slowing down the decline of renal function in order to reduce not only the occurrence of critical renal events (the need for dialysis or renal transplantation, among the most dreadful) but also the incidence of cardiovascular events. Accordingly, an early diagnosis and a targeted treatment in patients with kidney disease are crucial to reduce the evolution towards more advanced stages of the disease and the occurrence of complications. For a long time, the therapeutic approach to the majority of CKD patients was based on the strict control of risk factors, such as the diabetic disease and hypertension, together with the use of renin–angiotensin–aldosterone system inhibitors, particularly in the presence of albuminuria. Over time, this strategy proved to be only partially effective, since most CKD patients showed a progressive worsening of renal function. Gliflozins and incretins are novel anti-diabetic drugs that have been demonstrated to slow down the slope of eGFR reduction in patients with CKD, irrespective of diabetic status. Concurrently, these drugs showed to significantly impact cardiovascular prognosis reducing the incidence of clinical events. For their ability to act on a wide spectrum of disease, gliflozins and incretins are also called ‘cardio–nephro–metabolic’ drugs.
Causes of sudden death
Authors: De Gaspari Monica , Rizzo Stefania , Thiene Gaetano , Basso Cristina 
Published: April 2023

Abstract
Sudden cardiac death (SCD) pathophysiological point of view can be either mechanical or electrical. In case of mechanical SCD, the most frequent causes are pulmonary thromboembolism and cardiac tamponade due to intrapericardial rupture (aortic dissection, heart rupture). This distinction is important because cardiac arrest retains survival potential through cardiopulmonary resuscitation and defibrillators only if the rhythm is shockable. The heart diseases that can cause SCD vary according to the age of the individual. In young people, primary electrical diseases (‘ion channel diseases’) and cardiomyopathies (particularly hypertrophic and arrhythmogenic), both genetically determined and therefore potentially recurred in the proband’s family, as well as myocarditis and coronary anomalies prevail; in adult–elderly populations, coronary atherosclerosis with its complications and degenerative valve diseases (aortic stenosis and mitral valve prolapse) predominate. In this short text, the main structural heart diseases characterized by electrical instability at risk of SCD will be recalled, with a focus on coronary, myocardial, and valvular diseases.
Treg-based immunotherapy for antigen-specific immune suppression and stable tolerance induction: a perspective
Authors: Sakaguchi Shimon , Kawakami Ryoji , Mikami Norihisa 
Published: April 2023

Summary
FoxP3-expressing regulatory T cells (Tregs), whether naturally generated in the immune system or unnaturally induced from conventional T cells (Tconvs) in the laboratory, have much therapeutic value in treating immunological diseases and establishing transplantation tolerance. Natural Tregs (nTregs) can be selectively expanded in vivo by administration of low-dose IL-2 or IL-2 muteins for immune suppression. For adoptive Treg cell therapy, nTregs can be expanded in vitro by strong antigenic stimulation in the presence of IL-2. Synthetic receptors such as CAR can be expressed in nTregs to equip them with a particular target specificity for suppression. In addition, antigen-specific Tconvs can be converted in vitro to functionally stable Treg-like cells by a combination of antigenic stimulation, FoxP3 induction, and establishment of the Treg-type epigenome. This review discusses current and prospective strategies for Treg-based immune suppression and the issues to be resolved for achieving stable antigen-specific immune suppression and tolerance induction in the clinic by targeting Tregs.
Knowledge of tropical diseases and response capabilities of healthcare providers in Kaduna State, Nigeria
Authors: Adje David U , Dambo Edmund D 
Published: April 2023

Abstract

Background
The public health impact of neglected tropical diseases (NTDs) is quite substantial. The objective of this study was to assess the knowledge and response capability of health professionals regarding NTDs in Kaduna State, Nigeria.

Methods
A pre-tested questionnaire with a Cronbach's α coefficient of 0.716 was administered to 350 health professionals. The questionnaire assessed the knowledge, resource availability and capacity to handle NTD cases.

Results
Only 38 (12.6%) respondents were familiar with the World Health Organization's definition of NTDs. Although self-reported knowledge was highest for physicians (37 [82.2%]), there was no statistically significant knowledge disparity between cadres of health professionals. Only 12 (46.2%) practitioners in private health facilities reported adequate knowledge. The tier of practice was significantly associated with management of NTDs (χ2 = 10.545; df 2; p = 0.005). Only 24 (47.1%) medical laboratory scientists and 18 (40.0%) physicians had adequate clinical resources for management of NTDs. Nearly three-quarters (211 (70.1%)] of respondents had never been trained in the management of NTDs. More than half (177 [58.8%]) of facilities lacked pharmaceuticals or standard operating procedures for management of NTDs.

Conclusions
Self-reported knowledge of NTDs was suboptimal. Physical and clinical resources for the diagnosis and treatment of NTDs were inadequate. Targeted training, increased funding and provision of adequate resources are needed in order to ameliorate the situation.
Worse Itch and Fatigue in Racial and Ethnic Minorities: A Burn Model System Study
Authors: Won Paul , Stoycos Sarah A , Ding Li , McMullen Kara A , Kowalske Karen , Stewart Barclay T , Yenikomshian Haig A 
Published: April 2023

Abstract
Racial and ethnic minority patients experience worse hypertrophic scars after burn injury than White patients. Subsequently, minority patients encounter differences in scar-related recovery domains such as itch and fatigue. This study examines disparities regarding postburn injury itch and fatigue in minority patients to better inform counseling and treatment considerations. From the multicenter National Institute of Disability, Independent Living and Rehabilitation Research Burn Model System Database (2015-2019), outcomes were analyzed at three time-points (discharge from index hospitalization, 6- and 12-months post-injury) using the 5D Itch and PROMIS-29 Fatigue measures. Multilevel linear mixed effects regression modeling analyzed associations between race/ethnicities and outcomes over time. Of 893 total patients, minority patients reported higher/worse itch scores at all time points compared to White patients. Itch scores were significantly higher for Black patients at 6 months (β = 1.42, P = .03) and 12 months (β = 3.36, P &lt; .001) when compared to White patients. Black patients reported higher fatigue scores than White patients at all time points. Fatigue scores were significantly higher for Hispanic/Latino patients at discharge (β = 6.17, P &lt; .001), 6 months (β = 4.49, P &lt; .001), and 12 months (β = 6.27, P &lt; .001) than White patients. This study supports investigation of potential factors leading to increased itch and fatigue such as sociocultural factors, disparities in healthcare access, and psychosocial impacts of these symptoms. In the short-term, minority patients may benefit from additional counseling and focused treatments addressing itch and fatigue after burn injury.
Statins synergize with phosphodiesterase type 5 inhibitors but not with selective estrogen receptor modulators to prevent myofibroblast transformation in an in vitro model of Peyronie’s disease
Authors: Ilg Marcus M , Ralph David J , Cellek Selim 
Published: April 2023

Abstract

Background
Peyronie’s disease (PD) is a fibrotic disorder characterized by plaque formation in the tunica albuginea (TA) of the penis, and we have previously shown that inhibition of transformation of TA-derived fibroblasts to myofibroblasts using a combination phosphodiesterase type 5 (PDE5) inhibitors and selective estrogen receptor modulators (SERMs) is effective in slowing the progression of early PD.

Aim
The study sought to investigate whether combinations of statins with PDE5 inhibitors or SERMs would affect myofibroblast transformation in vitro.

Methods
Primary fibroblasts were isolated from TA of patients with PD and stimulated with transforming growth factor β1 in the absence and presence of a range of concentrations of statins, PDE5 inhibitors, SERMs, and their combinations for 72 hours before quantifying α-smooth muscle actin using in-cell enzyme-linked immunosorbent assay.

Outcomes
The prevention of transforming growth factor β1–induced transformation of TA-derived fibroblasts to myofibroblasts was measured in vitro.

Results
Statins (simvastatin, lovastatin) inhibited myofibroblast transformation in a concentration-dependent manner with half maximal inhibitory concentration values of 0.77 ± 0.07 μM and 0.8 ± 0.13 μM, respectively. Simvastatin inhibited myofibroblast transformation in a synergistic fashion when combined with vardenafil (a PDE5 inhibitor; log alpha &gt;0). Combination of tamoxifen (a SERM) and simvastatin did not show synergy (log alpha &lt;0). When 3 drugs (simvastatin, vardenafil, and tamoxifen) were combined, the effect was not synergistic, but rather was additive.

Clinical implications
A combination of a statin with a PDE5 inhibitor might be useful in the clinic to slow the progression of the disease in patients with early PD; however, caution should be taken with such a combination because of the reported myopathy as a side effect.

Strengths and limitations
The use of primary human cells from patients with PD is a strength of this study. The mechanisms by which these drug classes exert synergy when used in combination was not investigated.

Conclusion
This is the first demonstration of an antifibrotic synergy between statins and PDE5 inhibitors.
Blisters and bullae over the skin graft site: a complication of the Coronary Artery Bypass Graft Surgery (CABG)
Authors: Baroudi Ihsan , Sleibi Amjad , Whbi Ibrahim , Khattab Najdat , Douri Thaer 
Published: April 2023

Abstract
Coronary artery bypass grafting is one of the most widely used interventions for patients with ischemic heart disease worldwide. Skin incision blistering after vein harvesting surgery has an estimated incidence rate of 7%. Our case emphasizes the importance of using the right way of applying and removing bandages to minimize incision skin complications.
Boerhaave syndrome following the use of Kambo from the Amazonian Phyllomedusa bicolor tree frog in Australia
Authors: Darlington Christopher R , Copertino Nicolas 
Published: April 2023

Abstract
This case report describes Boerhaave syndrome in an otherwise healthy male after Kambo use in Australia. Kambo is produced from the sections of the Phyllomedusa bicolor (Boddaert, 1772) tree frog. Also known as the giant leaf frog, two-coloured leaf frog, waxy-monkey tree frog and kambô, is native to South America. Its use is part of a traditional cleansing ceremony but has been adopted by the alternative health movement.
Personalized regenerative strategies and molecular diagnosis forin vitrofertilization success: a case report
Authors: Hernández-Melchor Dinorah , Madrazo Iván , Padilla-Viveros América , Camargo Felipe , López-Bayghen Esther 
Published: April 2023

AbstractLimited options are available for infertility associated with damaged or suboptimal tissues, typically the endometrium or ovaries. The goal of regenerative medicine is to restore function to specific tissues. Here, a 35-year-old female patient underwent two interventions of regenerative medicine: (i) autologous mesenchymal stem cells (MSCs) were applied in the myometrium, and (ii) intraovarian infusion of platelet-rich plasma (PRP). After two failed in vitro fertilization cycles (IVF), in which the endometrium was &lt;5 mm, MSCs were applied, achieving a 7 mm trilaminar lining; however, the embryo quality remained poor. Therefore, intraovarian PRP was utilized for the next IVF cycle; the patient’s response improved, and a euploid embryo developed. After the embryo transfer and a normal 38 weeks of pregnancy, a baby girl was born. Here, we demonstrate two forms of regenerative medicine that can be utilized to improve IVF.
Is There a Wave of Right-Wing Terrorism? A Review Article
Authors: Byman Daniel 
Published: April 2023

Abstract
This review article examines whether right-wing terrorism in the United States and other countries constitutes a long-lasting “wave” comparable to anarchist, jihadist, and other causes that led to extremist violence. Past waves offer many lessons for understanding, and countering, the current right-wing terrorist surge. The various right-wing movement’s uses of technology, fragmentation into numerous groups and individual actors, and potential sources of decline—especially their regular interactions with law enforcement—all have historical parallels with other terrorism eras from which we can learn. However, the media focus on the current manifestations of right-wing violence obscures the deep historical roots of the movement: its violence is hardly new or otherwise unique to today, and thus it is not realistic to expect it to fade over time as movements like anarchism did a century ago. In addition, the international ties of right-wing groups and figures, while quite real, are less extensive and consequential than those of jihadists and many other groups in the past. Perhaps the most important and most difficult issue is the overlap between extreme right-wing violence and legitimate politics. This is a vulnerability but also a tremendous source of potential power, magnifying the influence of violent extremists and making counterterrorism more difficult. Resourcing the fight against far-right violence is vital, as is harnessing the power of technology companies. Finally and most difficult, the political dynamics must change, with politicians of all stripes condemning the violent extreme even as robust, and at times contentious, ideas remain part of the public debate.