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  • 1
    Online Resource
    Online Resource
    Combined Echocardiographic and Cardiopulmonary Exercise to Assess Determinants of Exercise Limitation in Chronic Obstructive Pulmonary Disease
    Elsevier BV ; 2021
    In:  Journal of the American Society of Echocardiography Vol. 34, No. 2 ( 2021-02), p. 146-155.e5
    Details
    In: Journal of the American Society of Echocardiography, Elsevier BV, Vol. 34, No. 2 ( 2021-02), p. 146-155.e5
    Type of Medium: Online Resource
    ISSN: 0894-7317
    URL: Article
    DOI: 10.1016/j.echo.2020.09.014
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
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  • 2
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    Preventing post-stroke dementia. The MARCH Trial. Protocol and statistical analysis plan of a randomized clinical trial testing the safety and efficacy of Maraviroc in post-stroke cognitive impairment
    SAGE Publications ; 2022
    In:  European Stroke Journal Vol. 7, No. 3 ( 2022-09), p. 314-322
    Details
    In: European Stroke Journal, SAGE Publications, Vol. 7, No. 3 ( 2022-09), p. 314-322
    Abstract: Current evidence suggest that 25%–33% of stroke-survivors develop post-stroke cognitive impairment (PSCI). The licensed drug Maraviroc, a CCR5-antagonist, is postulated to act via a neuroprotective mechanism that may offer the potential of preventing progression to vascular dementia. Our hypothesis: Maraviroc may have the potential to augment learning skills and cognitive performance by affecting synaptic plasticity, along with neuro-inflammatory modulation in patients with cerebral small vessel disease (SVD) and PSCI. Design: MARCH is a multi-center, double-blind randomized-control Phase-II trial of Maraviroc 150 or 600 mg/day versus placebo for 12-months in five stroke centers in Israel. Included are patients diagnosed with recent (1–24 months) subcortical stroke who experience mild PSCI and have evidence of white matter lesions and SVD on neuroimaging. Outcomes: Primary outcomes: 1. Change in cognitive scores. 2. Drug related adverse events. Secondary outcomes: change in functional and affective scores, MRI-derived measures, inflammatory markers, carotid atherosclerosis, cerebrospinal-fluid biomarkers in a sub-study. A sample size of 60 in each treatment group and 30 in the placebo group (total – 150 participants) provides 80% power between the treatment and the placebo groups. Conclusions: The results of this work could lead to a novel, readily available, therapeutic avenue to reduce PSCI, and possibly other pathologies. This study will test safety and effectiveness of Maraviroc in limiting cognitive deterioration and/or post stroke cognitive impairment in patients with cerebral small vessel disease. Schedule: First-patient first-visit was May 2021. Recruitment to complete in 2023, follow-up to complete in 2024.
    Type of Medium: Online Resource
    ISSN: 2396-9873 , 2396-9881
    URL: Article
    DOI: 10.1177/23969873221098857
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2022
    detail.hit.zdb_id: 2851287-X
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  • 3
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    Successful conservative management of left ventricular assist device candidates
    Wiley ; 2023
    In:  ESC Heart Failure Vol. 10, No. 1 ( 2023-02), p. 601-615
    Details
    In: ESC Heart Failure, Wiley, Vol. 10, No. 1 ( 2023-02), p. 601-615
    Abstract: Clinical trials comparing LVADs vs. conservative therapy were performed before the availability of novel medications or used suboptimal medical therapy. This study aimed to report that long‐term stabilization of patients entering a left ventricular assist device (LVAD) programme is possible with the use of aggressive conservative therapy. This is important because the excellent clinical stabilization provided by LVADs comes at the expense of significant complications. Methods and results This study was a single‐centre prospective evaluation of consecutive patients with advanced heart failure (HF) fulfilling criteria for LVAD implantation based on clinical and echocardiographic characteristics, cardiopulmonary exercise test, and right heart catheterization results. Their initial therapy included inotropes, thiamine, beta‐blockers, digoxin, spironolactone, hydralazine, and nitrates followed by the introduction of novel HF therapies. Coronary revascularization and cardiac resynchronization therapy were performed when indicated, and all patients were closely followed at our outpatient clinic. During the study period, 28 patients were considered suitable for LVAD implantation (mean age 63 ± 10.8 years, 92% men, 78% ischaemic, median HF duration 4 years). Clinical stabilization was achieved and maintained in 21 patients (median follow‐up 20 months, range 9–38 months). Compared with baseline evaluation, cardiac index increased from 2.05 (1.73–2.28) to 2.88 (2.63–3.55) L/min/m 2 , left ventricular end‐diastolic diameter decreased from 65.5 (62.4–66) to 58.3 (53.8–62.5) mm, and maximal oxygen consumption increased from 10.1 (9.2–11.3) to 16.1 (15.3–19) mL/kg/min. Three patients died and only four ultimately required LVAD implantation. Conclusions Notwithstanding the small size of our cohort, our results suggest that LVAD implantation could be safely deferred in the majority of LVAD candidates.
    Type of Medium: Online Resource
    ISSN: 2055-5822 , 2055-5822
    URL: Issue
    URL: Article
    DOI: 10.1002/ehf2.v10.1
    DOI: 10.1002/ehf2.14223
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2814355-3
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  • 4
    Online Resource
    Online Resource
    Table_1.docx
    Frontiers Media SA ; 2023
    In:  Frontiers in Cardiovascular Medicine Vol. 10 ( 2023-2-6)
    Details
    In: Frontiers in Cardiovascular Medicine, Frontiers Media SA, Vol. 10 ( 2023-2-6)
    Abstract: We aimed to test the differences in peak VO 2 between males and females in patients diagnosed with heart failure (HF), using combined stress echocardiography (SE) and cardiopulmonary exercise testing (CPET). Methods Patients who underwent CPET and SE for evaluation of dyspnea or exertional intolerance at our institution, between January 2013 and December 2017, were included and retrospectively assessed. Patients were divided into three groups: HF with preserved ejection fraction (HF p EF), HF with mildly reduced or reduced ejection fraction (HF mr EF/HF r EF), and patients without HF (control). These groups were further stratified by sex. Results One hundred seventy-eight patients underwent CPET-SE testing, of which 40% were females. Females diagnosed with HF p EF showed attenuated increases in end diastolic volume index ( P = 0.040 for sex × time interaction), significantly elevated E/e' ( P & lt; 0.001), significantly decreased left ventricle (LV) end diastolic volume:E/e ratio ( P = 0.040 for sex × time interaction), and lesser increases in A-VO 2 difference ( P = 0.003 for sex × time interaction), comparing to males with HF p EF. Females diagnosed with HF mr EF/HF r EF showed diminished increases in end diastolic volume index ( P = 0.050 for sex × time interaction), mostly after anaerobic threshold was met, comparing to males with HF mr EF/HF r EF. This resulted in reduced increases in peak stroke volume index ( P = 0.010 for sex × time interaction) and cardiac output ( P = 0.050 for sex × time interaction). Conclusions Combined CPET-SE testing allows for individualized non-invasive evaluation of exercise physiology stratified by sex. Female patients with HF have lower exercise capacity compared to men with HF. For females diagnosed with HF p EF, this was due to poorer LV compliance and attenuated peripheral oxygen extraction, while for females diagnosed with HF mr EF/HF r EF, this was due to attenuated increase in peak stroke volume and cardiac output. As past studies have shown differences in clinical outcomes between females and males, this study provides an essential understanding of the differences in exercise physiology in HF patients, which may improve patient selection for targeted therapeutics.
    Type of Medium: Online Resource
    ISSN: 2297-055X
    URL: Article
    URL: Article
    DOI: 10.3389/fcvm.2023.1098395
    DOI: 10.3389/fcvm.2023.1098395.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2781496-8
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  • 5
    Online Resource
    Online Resource
    Repetitive milrinone therapy in ambulatory advanced heart failure patients
    Wiley ; 2022
    In:  Clinical Cardiology Vol. 45, No. 5 ( 2022-05), p. 488-494
    Details
    In: Clinical Cardiology, Wiley, Vol. 45, No. 5 ( 2022-05), p. 488-494
    Abstract: Advanced heart failure (HF) patients usually poorly tolerate guideline‐directed HF medical therapy (GDMT) and suffer high rates of morbidity and mortality. The use of continuous inotropes in the outpatient settings is hampered by previous data showing excess morbidity. We aimed to assess the safety and efficacy of repetitive, intermittent, short‐term intravenous milrinone therapy in advanced HF patients with an intention to introduce and up‐titrate GDMT and improve functional class. Hypothesis Repetitive, intermittent milrinone therapy may assist with the stabilization of advanced HF patients. Methods Advanced HF patients treated with beta‐blockers and implanted with defibrillators were initiated with repetitive, intermittent short‐term intravenous milrinone therapy at our HF outpatient unit. Patients were prospectively followed with defibrillator interrogation, functional class assessment, B‐natriuretic peptide (BNP) levels, and echocardiography parameters. Results The cohort included 24 patients with a mean 330 ± 240 days of milrinone therapy exposure. Mean age was 73 ± 6 years with male predominance (96%). Following milrinone therapy, median BNP levels decreased significantly (882 [286−3768] to 631 [278−1378] pg/ml, p  = .017) with a significant reduction in the number of patients with New York Heart Association (NYHA) Class III and IV ( p  = .012, 0.013) and an increase in number of patients on GDMT. Importantly, the number of total sustained ventricular tachycardia events and HF hospitalizations did not change. Conclusions In this small cohort of advanced HF, repetitive, intermittent, short‐term milrinone therapy was found to be safe and potentially efficacious.
    Type of Medium: Online Resource
    ISSN: 0160-9289 , 1932-8737
    URL: Issue
    URL: Article
    DOI: 10.1002/clc.v45.5
    DOI: 10.1002/clc.23802
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2048223-1
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  • 6
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    Circle of Willis integrity in acute middle cerebral artery occlusion: does the posterior communicating artery matter?
    BMJ ; 2023
    In:  Journal of NeuroInterventional Surgery
    Details
    In: Journal of NeuroInterventional Surgery, BMJ
    Abstract: Collateral circulation is an important determinant of outcome in people with acute ischemic stroke due to large vessel occlusion (LVO). Objective To explore the impact of the circle of Willis (CW) anatomical characteristics ipsilateral to the occlusion site, particularly the posterior communicating artery (PComA) and the A1-portion of the anterior cerebral artery (A1-ACA), on stroke outcomes in a cohort of patients with LVO and middle cerebral artery (MCA) occlusion, undergoing endovascular thrombectomy (EVT). Methods This is a retrospective cohort study performed in a comprehensive tertiary stroke center. The study population consisted of consecutive patients with LVO with proximal MCA occlusion (M1) between June 2016 and April 2021, undergoing EVT. Demographic, clinical, and imaging information was extracted from patient files. Patency and diameters of ipsilateral A1-ACA and PComA were manually measured on admission CT angiography images in the core laboratory. Results One hundred and five patients with LVO comprised the study cohort, mean age 72.3 years, 43.8% were male, mean National Institutes of Health Stroke Scale score at admission 15.2. The cohort was grouped according to CW vessel characteristics. On univariate analysis, a well-developed PComA was associated with lower rates of hemorrhagic transformation (1.8% vs 14.3%, P=0.01) and a trend towards lower mortality rates (8.9% vs 20.4%, P=0.08).On multivariable regression analysis a well-developed PComA emerged as an independent predictor for survival (aOR=0.09, 95% CI 0.01 to 0.4 for survival at discharge, P=0.009, aOR=0.22, 95% CI 0.05 to 0.8 for survival at 90 days, P=0.02). Conclusions In a cohort of patients with LVO due to M1 occlusion undergoing EVT, a well-developed PComA was associated with significantly lower hemorrhagic transformation rates, a trend towards better functional outcomes, and independently predicted survival. Larger studies are needed to understand the differential effect of CW collateral conduits on stroke outcome and evaluate the practicality of incorporating such factors in the clinical decision-making process prior to EVT.
    Type of Medium: Online Resource
    ISSN: 1759-8478 , 1759-8486
    URL: Article
    DOI: 10.1136/jnis-2023-020326
    Language: English
    Publisher: BMJ
    Publication Date: 2023
    detail.hit.zdb_id: 2506028-4
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  • 7
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    Reply to: Timing of puberty — body size or reproductive optimization?
    Springer Science and Business Media LLC ; 2021
    In:  Nature Reviews Endocrinology Vol. 17, No. 9 ( 2021-09), p. 573-574
    Details
    In: Nature Reviews Endocrinology, Springer Science and Business Media LLC, Vol. 17, No. 9 ( 2021-09), p. 573-574
    Type of Medium: Online Resource
    ISSN: 1759-5029 , 1759-5037
    URL: Article
    DOI: 10.1038/s41574-021-00502-4
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2489384-5
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  • 8
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    Online Resource
    Srd5a1 is Differentially Regulated and Methylated During Prepubertal Development in the Ovary and Hypothalamus
    The Endocrine Society ; 2023
    In:  Journal of the Endocrine Society Vol. 7, No. 10 ( 2023-08-28)
    Details
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 7, No. 10 ( 2023-08-28)
    Abstract: 5α-reductase-1 catalyzes production of various steroids, including neurosteroids. We reported previously that expression of its encoding gene, Srd5a1, drops in murine ovaries and hypothalamic preoptic area (POA) after early-life immune stress, seemingly contributing to delayed puberty and ovarian follicle depletion, and in the ovaries the first intron was more methylated at two CpGs. Here, we hypothesized that this CpG-containing locus comprises a methylation-sensitive transcriptional enhancer for Srd5a1. We found that ovarian Srd5a1 mRNA increased 8-fold and methylation of the same two CpGs decreased up to 75% between postnatal days 10 and 30. Estradiol (E2) levels rise during this prepubertal stage, and exposure of ovarian cells to E2 increased Srd5a1 expression. Chromatin immunoprecipitation in an ovarian cell line confirmed ESR1 binding to this differentially methylated genomic region and enrichment of the enhancer modification, H3K4me1. Targeting dCas9-DNMT3 to this locus increased CpG2 methylation 2.5-fold and abolished the Srd5a1 response to E2. In the POA, Srd5a1 mRNA levels decreased 70% between postnatal days 7 and 10 and then remained constant without correlation to CpG methylation levels. Srd5a1 mRNA levels did not respond to E2 in hypothalamic GT1-7 cells, even after dCas9-TET1 reduced CpG1 methylation by 50%. The neonatal drop in POA Srd5a1 expression occurs at a time of increasing glucocorticoids, and treatment of GT1-7 cells with dexamethasone reduced Srd5a1 mRNA levels; chromatin immunoprecipitation confirmed glucocorticoid receptor binding at the enhancer. Our findings on the tissue-specific regulation of Srd5a1 and its methylation-sensitive control by E2 in the ovaries illuminate epigenetic mechanisms underlying reproductive phenotypic variation that impact life-long health.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    URL: Article
    DOI: 10.1210/jendso/bvad108
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2023
    detail.hit.zdb_id: 2881023-5
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  • 9
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    High parathyroid hormone levels after parathyroidectomy for parathyroid adenoma are not related to the cellularity of the remaining glands
    Wiley ; 2021
    In:  Laryngoscope Investigative Otolaryngology Vol. 6, No. 5 ( 2021-10), p. 1220-1227
    Details
    In: Laryngoscope Investigative Otolaryngology, Wiley, Vol. 6, No. 5 ( 2021-10), p. 1220-1227
    Abstract: Patients with primary hyperparathyroidism (PHPT) treated surgically occasionally have normalized calcium, but persistently high parathyroid hormone (PTH). We hypothesized that a possible explanation for this phenomenon is an underlying hyperplasia rather than adenoma. Methods Retrospective cohort of patients who underwent parathyroidectomy for PHPT with biopsy of a normal‐appearing parathyroid gland were included. Cellularity level of each biopsy and of the adenoma's rim was determined. Results Forty‐seven patients were included. Of them, 19 (40%) had postoperative normocalcemia but elevated PTH. There was no correlation between cellularity either in the rim or of the normal‐appearing parathyroid gland and postoperative PTH. The postoperative high PTH group had higher preoperative PTH ( P  = 0.001) and larger adenomas ( P  = 0.025). Conclusions High PTH levels after successful parathyroidectomy in patients with primary hyperparathyroidism do not appear to result from underlying hyperplasia. A possible alternative explanation is that these patients have a higher preoperative burden of disease.
    Type of Medium: Online Resource
    ISSN: 2378-8038 , 2378-8038
    URL: Issue
    URL: Article
    DOI: 10.1002/lio2.v6.5
    DOI: 10.1002/lio2.644
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2851702-7
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  • 10
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    The Large Array Survey Telescope—System Overview and Performances
    IOP Publishing ; 2023
    In:  Publications of the Astronomical Society of the Pacific Vol. 135, No. 1048 ( 2023-06-01), p. 065001-
    Details
    In: Publications of the Astronomical Society of the Pacific, IOP Publishing, Vol. 135, No. 1048 ( 2023-06-01), p. 065001-
    Abstract: The Large Array Survey Telescope (LAST) is a wide-field visible-light telescope array designed to explore the variable and transient sky with a high cadence. LAST will be composed of 48, 28 cm f/2.2 telescopes (32 already installed) equipped with full-frame backside-illuminated cooled CMOS detectors. Each telescope provides a field of view (FoV) of 7.4 deg 2 with 1.″25 pix −1 , while the system FoV is 355 deg 2 in 2.9 Gpix. The total collecting area of LAST, with 48 telescopes, is equivalent to a 1.9 m telescope. The cost-effectiveness of the system (i.e., probed volume of space per unit time per unit cost) is about an order of magnitude higher than most existing and under-construction sky surveys. The telescopes are mounted on 12 separate mounts, each carrying four telescopes. This provides significant flexibility in operating the system. The first LAST system is under construction in the Israeli Negev Desert, with 32 telescopes already deployed. We present the system overview and performances based on the system commissioning data. The B p 5 σ limiting magnitude of a single 28 cm telescope is about 19.6 (21.0), in 20 s (20 × 20 s). Astrometric two-axes precision (rms) at the bright-end is about 60 (30) mas in 20 s (20 × 20 s), while absolute photometric calibration, relative to GAIA, provides ∼10 millimag accuracy. Relative photometric precision, in a single 20 s (320 s) image, at the bright-end measured over a timescale of about 60 minutes is about 3 (1) millimag. We discuss the system science goals, data pipelines, and the observatory control system in companion publications.
    Type of Medium: Online Resource
    ISSN: 0004-6280 , 1538-3873
    URL: Article
    DOI: 10.1088/1538-3873/acd8f0
    Language: Unknown
    Publisher: IOP Publishing
    Publication Date: 2023
    detail.hit.zdb_id: 2003100-2
    detail.hit.zdb_id: 2207655-4
    SSG: 16,12
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