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1.
PLoS One ; 16(8): e0255740, 2021.
Article in English | MEDLINE | ID: mdl-34352035

ABSTRACT

OBJECTIVE: The optimal surgical approach for critically ill patients with complex coronary disease remains uncertain. We compared outcomes of bilateral internal thoracic artery (BITA) versus single ITA (SITA) revascularization in critical patients. METHODS: We evaluated 394 consecutive critical patients with multi-vessel disease who underwent CABG during 1996-2001. Outcomes measured were early mortality, strokes, myocardial-infarctions, sternal infections, revisions for bleeding, and late survival. The critical preoperative state was acknowledged concisely by one or more of the following: preoperative ventricular tachycardia/fibrillation, aborted sudden cardiac death, or the need for mechanical ventilation or for preoperative insertion of intra-aortic-balloon counter-pulsation. RESULTS: During the study period, 193 of our patients who underwent SITA and 201 who underwent BITA were in critical condition. The SITA group was older (mean 68.0 vs. 63.3 years, p = 0.001) and higher proportions were females (28.5% vs. 18.9% p = 0.025), after recent-MI (69.9% vs. 57.2% p = 0.009) and with left-main disease (38.3% vs. 49.3% p = .029); the median logistic EuroSCORE was higher (0.2898 vs. 0.1597, p<0.001). No statistically significant differences were observed between the SITA and BITA groups in 30-day mortality; and in rates of early CVA, MI and sternal infections (13.0% vs. 8.5%, p = 0.148; 4.1% vs. 6.0%, p = 0.49; 6.7% vs. 4.5%, p = 0.32 and 2.1% vs. 2.5%, p>0.99, respectively). Long-term survival (median follow-up of 15 years, interquartile-range: 13.57-15) was better in the BITA group (median 14.39 vs. 9.31± 0.9 years, p = 0.001). Propensity-score matching (132 matched pairs) also yielded similar early outcomes and improved long-term survival (median follow-up of 15 years, interquartile-range: 13.56-15) for the BITA group (median 12.49±1.71 vs. 7.63±0.99 years, p = 0.002). In multivariable analysis, BITA revascularization was found to be a predictor for improved survival (hazard-ratio of 0.419, 95%CI 0.23-0.76, p = 0.004). CONCLUSIONS: This study demonstrated long-term survival benefit for BITA revascularization in patients in a critical pre-operative state who presented for surgical revascularization.


Subject(s)
Coronary Disease/surgery , Myocardial Revascularization/methods , Postoperative Complications/epidemiology , Aged , Critical Care , Female , Humans , Male , Middle Aged , Myocardial Revascularization/adverse effects , Survival Analysis , Thoracic Arteries/surgery
2.
EMBO Rep ; 18(7): 1166-1185, 2017 07.
Article in English | MEDLINE | ID: mdl-28588072

ABSTRACT

A pathologic osteochondrogenic differentiation of vascular smooth muscle cells (VSMCs) promotes arterial calcifications, a process associated with significant morbidity and mortality. The molecular pathways promoting this pathology are not completely understood. We studied VSMCs, mouse aortic rings, and human aortic valves and showed here that histone deacetylase 4 (HDAC4) is upregulated early in the calcification process. Gain- and loss-of-function assays demonstrate that HDAC4 is a positive regulator driving this pathology. HDAC4 can shuttle between the nucleus and cytoplasm, but in VSMCs, the cytoplasmic rather than the nuclear activity of HDAC4 promotes calcification, and a nuclear-localized mutant of HDAC4 fails to promote calcification. The cytoplasmic location and function of HDAC4 is controlled by the activity of salt-inducible kinase (SIK). Pharmacologic inhibition of SIK sends HDAC4 to the nucleus and inhibits the calcification process in VSMCs, aortic rings, and in vivo In the cytoplasm, HDAC4 binds and its activity depends on the adaptor protein ENIGMA (Pdlim7) to promote vascular calcification. These results establish a cytoplasmic role for HDAC4 and identify HDAC4, SIK, and ENIGMA as mediators of vascular calcification.


Subject(s)
Gene Expression Regulation , Histone Deacetylases/genetics , Protein Serine-Threonine Kinases/metabolism , Protein-Tyrosine Kinases/metabolism , Repressor Proteins/genetics , Vascular Calcification/physiopathology , Adaptor Proteins, Signal Transducing/genetics , Animals , Aortic Valve/physiopathology , Cell Differentiation , Cell Nucleus , Cytoplasm/chemistry , Cytoplasm/metabolism , Cytoskeletal Proteins/genetics , Histone Deacetylases/metabolism , Humans , Intracellular Signaling Peptides and Proteins/genetics , LIM Domain Proteins/genetics , Mice , Muscle, Smooth, Vascular/pathology , Protein Serine-Threonine Kinases/genetics , Protein-Tyrosine Kinases/genetics , Repressor Proteins/metabolism , Signal Transduction , Up-Regulation , Vascular Calcification/genetics
5.
Harefuah ; 153(8): 487-8, 496, 2014 Aug.
Article in Hebrew | MEDLINE | ID: mdl-25286643

ABSTRACT

At the beginning of the 1960's, three female doctors managed to break the glass ceiling and become the first female cardiothoracic surgeons in the USA. Since then, the number of certified female cardiothoracic surgeons has steadily increased. Nevertheless, females stilt only account for a minority of cardiothoracic surgeons in the USA. In Israel, three women have become specialists in cardiothoracic surgery over the last two decades, aLthough these surgeons are working as general thoracic surgery consultants, without any representative females in cardiac surgery.


Subject(s)
Physicians, Women , Thoracic Surgery , Female , Humans , Israel , Job Satisfaction , Physicians, Women/psychology , Physicians, Women/statistics & numerical data , Physicians, Women/trends , Specialty Boards/statistics & numerical data , Thoracic Surgery/trends , United States , Workforce
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