bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of Hypertension Because of Immunosuppressive Therapy After Solid Organ Transplantation—Pharmacological Approach
Authors: Gilewski Wojciech , Banach Joanna , Rogowicz Daniel , Wołowiec Łukasz , Sielski Sławomir , Grześk Grzegorz 
Published: May 2021

Abstract:
Solid organs transplantation procedures have been performed for more than half a century. Growing knowledge of immune response and development of new immunosuppressive regimens guarantee more and more successful outcomes. However, many of the applied drugs lead to cardiovascular complications, the most frequent of which is hypertension. This article describes epidemiology, pathogenetic mechanisms, and treatment of hypertension induced by immunosuppressive medication. The main impact is focused on drugs belonging to the following groups: calcineurin inhibitors, the inhibitors of the mammalian target of rapamycin, and glucocorticosteroids. We analyze the mechanism of action of the main hypertensive drugs and their influence on the reversing hypertonic action of the immunosuppressive agents. In the absence of current guidelines addressing this problem, this article is an attempt to fill the gap, helping clinicians to choose proper medication.
Effect of Levosimendan on Ventricular Systolic and Diastolic Functions in Heart Failure Patients: A Meta-Analysis of Randomized Controlled Trials
Authors: Long Yu-Xiang , Cui Di-Yu , Kuang Xue , Hu Shuang , Hu Yue , Liu Zeng-Zhang 
Published: May 2021

Abstract:
Levosimendan, a calcium sensitizer, exerts inotropic action through improving left ventricular ejection fraction. We noticed that only few clinical studies are published in which the effects of levosimendan on cardiac function are studied by echocardiography. When screening the literature (PubMed, Embase, and CENTRAL, from inception to August 2020), we found 29 randomized controlled trials on levosimendan containing echocardiographic data. We included those studies, describing a total of 574 heart failure patients, in our meta-analysis and extracted 14 ultrasonic parameters, pooling the effect estimates using a random-effect model. Our analysis of the diastolic parameters of the left ventricle shows that levosimendan reduce the early/late transmitral diastolic peak flow velocity ratio [standardized mean difference (SMD) −0.45 to 95% confidence interval (CI) (−0.87 to −0.03), P = 0.037] and E/e' (e': mitral annulus peak early diastolic wave velocity using tissue-doppler imaging) [SMD −0.59, 95% CI (−0.8 to −0.39), P < 0.001]. As it regards the systolic parameters of the right ventricle, levosimendan increased tricuspid annular plane systolic excursion [SMD 0.62, 95% CI (0.28 to 0.95), P < 0.001] and tricuspid annular peak systolic velocity [SMD 0.75, 95% CI (0.35 to 1.16), P < 0.001], and reduced systolic pulmonary artery pressure [SMD −1.02, 95% CI (−1.32, −0.73), P < 0.001]. As it regards the diastolic parameters of the right ventricle, levosimendan was associated with the decrease of Aa (peak late diastolic tricuspid annular velocity using tissue-doppler imaging) [SMD −0.38, 95% CI (−0.76 to 0), P = 0.047] and increase of Ea (peak early diastolic tricuspid annular velocity using tissue-doppler imaging) [SMD 1.03, 95% CI (0.63 to 1.42), P < 0.001] and Ea/Aa [SMD 0.86, 95% CI (0.18 to 1.54), P = 0.013]. We show that levosimendan is associated with an amelioration in the diastolic and systolic functions of both ventricles in heart failure patients.
Could Dapagliflozin Attenuate COVID-19 Progression in High-Risk Patients With or Without Diabetes? Behind DARE-19 Concept
Authors: Anastasiou Georgia , Hatziagelaki Erifili , Liberopoulos Evangelos 
Published: May 2021

Abstract:
Epidemiological studies indicate that diabetes is the second most common comorbidity in COVID-19 (coronavirus disease 2019). Dapagliflozin, a sodium-glucose co-transporter 2 inhibitor, exerts direct cardioprotective and nephroprotective effects. DARE-19 (Dapagliflozin in Respiratory Failure in Patients With COVID-19), an ongoing clinical trial, is designed to investigate the impact of dapagliflozin on COVID-19 progression. This article discusses the potential favorable impact of dapagliflozin on COVID-19 and its complications.
Aprocitentan (a Dual Endothelin-Receptor Antagonist) for Treatment-Resistant Hypertension
Authors: McCoy Emily K. , Lisenby Katelin M. 
Published: May 2021

Abstract:
Treatment-resistant hypertension (TRH) is associated with increased cardiovascular risks and progression of chronic kidney disease. The pathophysiology of TRH is multifactorial, including overactivity of the renin–angiotensin–aldosterone system and sympathetic nervous system, endothelial dysfunction, and volume overload. Endothelin-1 is a vasoconstrictive peptide that causes neurohormonal and sympathetic activation, increased aldosterone synthesis and secretion, endothelial dysfunction, vascular hypertrophy and remodeling, and fibrosis. Endothelin-1 acts through 2 receptors, ETA and ETB. Activation of ETA receptors in vascular smooth muscle cells results in vasoconstriction, whereas ETB receptor activation results in vasoconstriction in the vascular smooth muscle cells and vasodilation through nitric oxide release in endothelial cells. Aprocitentan is novel, oral, dual endothelin-receptor antagonist that has demonstrated a more favorable tolerability and safety profile in early clinical trials compared with other endothelin-receptor antagonists studied. Phase 2 trial data support a significant reduction in blood pressure compared to placebo and similar blood pressure reduction compared to a moderately dosed angiotensin-converting enzyme inhibitor in patients with essential hypertension. An ongoing phase 3 randomized clinical trial is evaluating aprocitentan's efficacy and safety in patients with TRH receiving multiple antihypertensives. Additional research is needed to determine aprocitentan's role in therapy, but this agent may be a suitable treatment option for TRH.
Takotsubo Cardiomyopathy as Epiphenomenon of Cardiotoxicity in Patients With Cancer: A Meta-summary of Case Reports
Authors: Carbone Andreina , Bottino Roberta , Russo Vincenzo , D'Andrea Antonello , Liccardo Biagio , Maurea Nicola , Quagliariello Vincenzo , Cimmino Giovanni , Golino Paolo 
Published: May 2021

Abstract:
Many antitumoral drugs have been linked to takotsubo cardiomyopathy, with no clear pathogenetic mechanisms. Data about this condition are lacking in literature. The aim of this meta-summary is to summarize the characteristics of patients with antitumoral drug–induced takotsubo cardiomyopathy, described in case reports available in literature. We searched for published case reports in PubMed, Google Scholar, EMBASE, and Scopus from 2009 about stress cardiomyopathy and antiblastic drugs. We selected 41 case reports. All cases underwent chemotherapy/immunotherapy for different types of cancer. The median age was 58 years, and 61% of them were women. The most common comorbidities were hypertension (12.2%) and dyslipidemia (4.9%), but most of the population had no cardiological clinical history. Takotsubo cardiomyopathy is associated to the 5-fluorouracil (36.5%), capecitabine (9.7%), trastuzumab (9.7%), and immune check point inhibitor (9.7%) treatment. The median time of onset was 2 days (1–150). Cardiogenic shock was the first manifestation in 11 patients (26.8%). Left ventricle ejection fraction recovery was showed in 33 patients (89%) with mean ejection fraction 57.7 ± 7%, after a median of 30-day (4–300) follow-up. Patients with cancer experienced takotsubo cardiomyopathy within few days from the beginning of therapy, and the most of them normalized the heart function in few weeks. Cardiogenic shock showed high prevalence in this setting of patients. Larger studies are needed to better understand the pathological mechanisms of antiblastic drug–induced stress cardiomyopathy, to find risk factors associated and preventive strategies for limit this type of cardiotoxicities.
Facial Feminization Surgery under Insurance: The University of California Los Angeles Experience
Authors: Hu Allison C. , Dang Brian N. , Bertrand Anthony A. , Jain Nirbhay S. , Chan Candace H. , Lee Justine C. 
Published: May 2021

Background:
Despite improved insurance coverage for gender confirmation surgeries in the United States, coverage for facial feminization surgery (FFS) continues to be difficult. Here, we describe our institutional experience on navigation, time, and costs of the FFS insurance authorization process.

Methods:
FFS consults (n = 40) at the University of California, Los Angeles (2018–2020) were reviewed for time and cost to definitive insurance authorization decision. Patients were stratified into 3 groups based on authorization process: Group A (standard approval, n = 26, 65.0%) including public and private insurances; Group B (extended approval, n = 10, 25.0%) consisting of private insurance plans that initially denied and required multi-level appeals for denial overturn; and Group C (denial, n = 4, 10.0%), including private insurance plans that denied even after multi-level appeals.

Results:
An estimated 90% of all patient consults were approved for FFS under insurance. Group A averaged 1.1 months for approval, requiring 1.4 hours of administrative time translating to $38.18 per patient. The addition of multi-level appeals in Groups B and C increased the total time for a definitive decision (7.0 and 5.1 months, respectively) and required both surgeon and administrative time to navigate the process (10.8 and 12.0 hours, respectively). The time spent on the presurgical authorization process for Groups B and C translated to an over 20-fold increase in cost ($855.00 and $988.38, respectively) compared with Group A.

Conclusion:
Navigation of the insurance process for FFS is challenging and time-consuming; however, coverage is a reality in California provided that multi-level appeals are exhausted.
Oral Beta-blocker in Problematic Infantile Hemangioma
Authors: AlHasan Rashed N. , Arabiyat Lamees , Ammar Hamad M. , Louri Nayef A. 
Published: May 2021

Summary:
One of the most common benign vascular endothelial tumors is infantile hemangioma. These lesions are commonly found in the head and neck, and sometimes it is a challenge to decide the method of treatment if the lesions are problematic hemangiomas, interfering with function or aesthetic appearance. This study reports a case of girl aged 3 years, 7 months, diagnosed with periorbital infantile hemangioma that was successfully treated with oral propranolol in specific doses and gradual tapering off dose. The patient had marked involution of the lesion with no significant side effects after starting her treatment at the age of 4 months, for a total of 13 months with no reported rebound growth after almost 2 years since the termination of treatment. Oral beta-blockers can be used safely in treatment of problematic infantile hemangioma as a single modality, without any surgical intervention.
Effectiveness of statin intensive therapy in type 2 diabetes mellitus with high visit-to-visit blood pressure variability
Authors: Ikeda Shota , Shinohara Keisuke , Enzan Nobuyuki , Matsushima Shouji , Tohyama Takeshi , Funakoshi Kouta , Kishimoto Junji , Itoh Hiroshi , Komuro Issei , Tsutsui Hiroyuki 
Published: May 2021

Background:
Intensive lipid-lowering therapy is recommended in type 2 diabetes mellitus (T2DM) patients with target organ damage. However, the evidence is insufficient to stratify the patients who will benefit from the intensive therapy among them. High visit-to-visit variability in systolic blood pressure (SBP) is associated with increased risk of cardiovascular events. We investigated the effectiveness of intensive versus standard statin therapy in the primary prevention of cardiovascular events among T2DM patients with retinopathy stratified by visit-to-visit SBP variability.

Methods:
The standard versus intensive statin therapy for hypercholesterolemic patients with diabetic retinopathy study was the first trial comparing statin intensive therapy targeting low-density lipoprotein cholesterol (LDL-C) <70 mg/dl and standard therapy targeting LDL-C ≥100 to <120 mg/dl in T2DM patients with retinopathy without known cardiovascular disease. Using this dataset, we divided the patients into two subpopulations based on standard deviation (SD) and average real variability (ARV) of clinic SBP within the initial 6 months.

Results:
In a total of 4899 patients, 240 composite cardiovascular events were observed during a median follow-up of 37.3 months. In multivariable-adjusted model comparing intensive versus standard therapy, the hazard ratios for composite cardiovascular events were 0.64 (95% CI 0.45–0.90) and 1.21 (95% CI 0.82–1.80) in patients with high and low SBP variability as defined by SD, respectively. Interaction between SBP variability and statin therapy was significant (P = 0.018). The analysis using ARV of SBP showed similar results.

Conclusion:
Statin intensive therapy targeting LDL-C <70 mg/dl had benefits in primary prevention of cardiovascular events compared with standard therapy among T2DM patients with retinopathy having high, but not low, visit-to-visit SBP variability.
Adaptation of left ventricular diastolic function to pregnancy: a systematic review and meta-analysis
Authors: de Haas Sander , Spaanderman Marc E.A. , van Kuijk Sander M.J. , van Drongelen Joris , Mohseni Zenab , Jorissen Laura , Ghossein-Doha Chahinda 
Published: May 2021

Objective:
To meta-analytically determine the adaptation of left ventricular diastolic function (LVDF)-indices to singleton normotensive pregnancies.

Methods:
Literature was retrieved from PubMed and Embase. We included studies that reported a nonpregnant reference measurement and LVDF indices (mitral inflow signals, left atrial volume and tissue Doppler measurements). Mean differences between pregnant and reference measurements and weighted means of absolute values were calculated using a random-effects model.

Results:
We included 34 eligible studies. Normotensive pregnancies were characterized by an initially larger increase in the passive left ventricular filling (E-wave peak velocity, 13%) compared to active left ventricular filling during diastole (A-wave peak velocity, 6%) resulting in a 16% increase of the E/A ratio in the first trimester. The E/A ratio progressively decreased during advancing gestation to −18% at term, resulting from stabilizing E-wave peak velocity and increased A-wave peak velocity. The E/e′ ratio was increased between 22 and 35 weeks (a maximal increase of 13%) in normotensive pregnancy. Left atrial volume (LAV) progressively increased from 15 weeks onwards with a maximal increase of 30% between 36 and 41 weeks.

Conclusion:
LVDF in normotensive pregnancy was improved in the first trimester after which LVDF progressively worsened. Large-scale studies in normotensive and hypertensive complicated pregnancies are needed for a more precise insight into LVDF changes during pregnancy.
An exploratory analysis of comparative plasma metabolomic and lipidomic profiling in salt-sensitive and salt-resistant individuals from The Dietary Approaches to Stop Hypertension Sodium Trial
Authors: Chaudhary Parul , Velkoska Elena , Wainford Richard D. 
Published: May 2021

Objective:
This study conducted exploratory metabolomic and lipidomic profiling of plasma samples from the DASH (Dietary Approaches to Stop Hypertension) Sodium Trial to identify unique plasma biomarkers to identify salt-sensitive versus salt-resistant participants.

Methods:
Utilizing plasma samples from the DASH-Sodium Trial, we conducted untargeted metabolomic and lipidomic profiling on plasma from salt-sensitive and salt-resistant DASH-Sodium Trial participants. Study 1 analyzed plasma from 106 salt-sensitive and 85 salt-resistant participants obtained during screening when participants consumed their regular diet. Study 2 examined paired within-participant plasma samples in 20 salt-sensitive and 20 salt-resistant participants during a high-salt and low-salt dietary intervention. To investigate differences in metabolites or lipidomes that could discriminate between salt-sensitive and salt-resistant participants or the response to a dietary sodium intervention Principal Component Analysis and Orthogonal Partial Least Square Discriminant Analysis was conducted. Differential expression analysis was performed to validate observed variance and to determine the statistical significance.

Results:
Differential expression analysis between salt-sensitive and salt-resistant participants at screening revealed no difference in plasma metabolites or lipidomes. In contrast, three annotated plasma metabolites, tocopherol alpha, 2-ketoisocaproic acid, and citramalic acid, differed significantly between high-sodium and low-sodium dietary interventions in salt-sensitive participants.

Conclusion:
In DASH-Sodium Trial participants on a regular diet, plasma metabolomic or lipidomic signatures were not different between salt-sensitive and salt-resistant participants. High-sodium intake was associated with changes in specific circulating metabolites in salt-sensitive participants. Further studies are needed to validate the identified metabolites as potential biomarkers that are associated with the salt sensitivity of blood pressure.
Implications of Cloth COVID Masks for Size Distribution of Inhaled Plutonium, Respiratory Deposition, and Fecal Bioassay Monitoring
Authors: Klumpp John , Poudel Deepesh 
Published: May 2021

Abstract
This work considers the implications of cloth masks due to the COVID-19 pandemic on suspected plutonium inhalations and dose assessment. In a plutonium inhalation scenario, the greater filtration efficiency for large particles exhibited by cloth masks can reduce early fecal excretion without a corresponding reduction in dose. For plutonium incidents in which cloth masks are worn, urinary excretion should be the preferred method of inferring dose immediately after the inhalation, and fecal excretion should be considered unreliable for up to 10 days.
GEOGRAPHIC ACCESS DISPARITIES TO CLINICAL TRIALS IN RETINOPATHY OF PREMATURITY IN THE UNITED STATES
Authors: Soares Rebecca R. , Cai Louis Z. , Bowe Theodore , Samuelson Annika G. , Liu Catherine K. , Parikh Devayu , Patel Samir N. , Hinkle John W. , Yonekawa Yoshihiro 
Published: May 2021

Background/Purpose:
To identify geographic and socioeconomic variables predictive of residential proximity to retinopathy of prematurity (ROP) clinical trial locations.

Methods:
This cross-sectional epidemiological study used census tract–level data from three national public data sets and trial-level data from ClinicalTrials.gov. Socioeconomic predictors of driving distance and time to the nearest ROP clinical trial location were identified. Primary outcomes were time >60 minutes and distance >60 miles traveled to the nearest ROP clinical trial site.

Results:
Multivariate analysis showed that residents were more likely to travel >60 minutes to the nearest ROP clinical trial site if they lived in census tracts that were rural (adjusted odds ratio 1.20, P = 0.0002), had higher percentages of the population living ≤ federal poverty level (fourth quartile vs. first quartile, adjusted odds ratio 1.19, P < 0.0001), or had less education (associate vs. bachelor's degree, adjusted odds ratio 1.01, P <0.007). By contrast, counties with higher percentages of births with birth weight <1500 g (adjusted odds ratio 0.88, P = 0.0062) were less likely to travel >60 minutes. Similar variables predicted travel distance.

Conclusion:
Although counties with higher incidences of very low-birth-weight infants were closer to ROP clinical trial sites, residents living in rural and low-income census tracts had significantly greater travel burdens.
MULTIMODAL IMAGING FINDINGS IN ACUTE WEST NILE VIRUS CHORIORETINITIS
Authors: Golshani Cyrus , Venkat Arthi , Srivastava Sunil K. 
Published: May 2021

Purpose:
To describe multimodal imaging findings of acute West Nile virus chorioretinitis.

Methods:
Observational case report. Fundus photographs, fluorescein angiography, indocyanine green angiography, and swept-source optical coherence tomography angiography were used to characterize and describe the clinical findings.

Results:
A 58-year-old man presented with acute painless vision loss in the right eye. Multimodal imaging demonstrated multifocal pinpoint early-phase hyperfluorescence with late expanding leakage on fluorescein angiography and late hyperfluorescence on indocyanine green angiography. Swept-source optical coherence tomography angiography en face imaging of the ellipsoid zone layer revealed target-like lesions with central hyperreflectivity with surrounding hyporeflectivity. At 4-week follow-up, the chorioretinal lesions now demonstrated greater demarcation of borders with increased pigmentation. At 8-week follow-up, fundus examination revealed multiple target-like lesions with hyperpigmentation centrally surrounded by a hypopigmented rim. Repeat fluorescein angiography demonstrated central hypofluorescence with surrounding hyperfluorescent staining rim prompting workup for West Nile virus, which was later confirmed by laboratory testing. The patient's visual acuity and clinical examination remained stable on subsequent follow-up visits.

Conclusion:
Our case highlights multimodal imaging findings in the acute phase of West Nile virus chorioretinitis, which may be crucial to early diagnosis and identification.
ADULT-ONSET BEST1-VITELLIFORM DYSTROPHY ASSOCIATED WITH ANGIOID STREAK-LIKE CHANGES IN TWO SIBLINGS
Authors: Li Yafeng , Bracha Peter , Aleman Tomas S. , Brucker Alexander J. 
Published: May 2021

Background/Purpose:
To describe the association between autosomal dominant Best disease and peripapillary angioid streak-like changes.

Methods:
Case report of two siblings.

Results:
A 76-year-old White man was referred for evaluation of bilateral macular changes and worsening visual distortion over the preceding 2 years. Best-corrected visual acuity measured 20/30 in the right eye and 20/80 in the left eye. Funduscopic examination revealed multifocal yellow lesions in the posterior pole that were hyperautofluorescent on short-wavelength excitation and corresponded with subretinal hyperreflective material on optical coherence tomography. The posterior pole examination was interesting because of the juxtapapillary involvement of the vitelliform lesions and the presence of bilateral peripapillary angioid streak-like changes despite no history of conditions associated with angioid streaks. On further workup, an electrooculogram revealed reduced Arden ratios and a known heterozygous missense mutation in BEST1 (c.903T>G; p.D301E) was found. The patient's 69-year-old younger brother was brought in and found to have a remarkably similar phenotype, including the presence of angioid streak-like changes associated with the same BEST1 mutation.

Conclusion:
These two cases demonstrate the possibility of late-onset multifocal vitelliform disease due to dominantly inherited BEST1. A consistent phenotype in this family with macular lesions extending into the peripapillary region, associated with angioid streak-like changes, suggests susceptibility of this region to changes in dominant BEST1-vitelliform macular dystrophy.