The N1-acetylation of spermidine and spermine by spermidine/spermine acetyltransferase (SSAT) is a crucial step in the regulation of the cellular polyamine levels in eukaryotic cells. Altered polyamine levels are associated with a variety of cancers as well as other diseases, and key enzymes in the polyamine pathway, including SSAT, are being explored as potential therapeutic drug targets. We have expressed and purified human SSAT in Escherichia coli and characterized its kinetic and chemical mechanism. Initial velocity and inhibition studies support a random sequential mechanism for the enzyme. The bisubstrate analogue, N1-spermine-acetyl-coenzyme A, exhibited linear, competitive inhibition against both substrates with a true Ki of 6 nM. The pH-activity profile was bell-shaped, depending on the ionization state of two groups exhibiting apparent pKa values of 7.27 and 8.87. The three-dimensional crystal structure of SSAT with bound bisubstrate inhibitor was determined at 2.3 A resolution. The structure of the SSAT-spermine-acetyl-coenzyme A complex suggested that Tyr140 acts as general acid and Glu92, through one or more water molecules, acts as the general base during catalysis. On the basis of kinetic properties, pH dependence, and structural information, we propose an acid/base-assisted reaction catalyzed by SSAT, involving a ternary complex.

Introduction Ultrasound guided axillary vein access (UGAVA) is an emerging approach for cardiac implantable electronic device (CIED) implantation not widely utilized. Methods and Results This is a retrospective, age and sex‐matched cohort study of CIED implantation from January 2017 to July 2019 comparing UGAVA before incision to venous access obtained after incision without ultrasound (conventional). The study population included 561 patients (187 with attempted UGAVA, 68 ± 13 years old, 43% women, body mass index (BMI) 30 ± 8 kg/m2, 15% right‐sided, 43% implantable cardioverter‐defibrillator, 15% upgrades). UGAVA was successful in 178/187 patients (95%). In nine patients where UGAVA was abandoned, the vein was too deep for access before incision. BMI was higher in abandoned patients than successful UGAVA (38 ± 6 vs. 28 ± 6 kg/m2, p < .0001). Median time from local anesthetic to completion of UGAVA was 7 min (interquartile range [IQR]: 4–10) and median procedure time 61 min (IQR: 50–92). UGAVA changed implant laterality in two patients (avoiding an extra incision in both) and could have prevented unnecessary incision in four conventional patients. Excluding device upgrades, there was reduced fluoroscopy time in UGAVA versus conventional (4 vs. 6 min; IQR: 2–5 vs. 4–9; p < .001). Thirty‐day complications were similar in UGAVA versus conventional (n = 7 vs. 26, 4 vs. 7%; p = .13, p = .41 adjusting for upgrades), partly driven by a trend towards reduced pneumothorax (n = 0 vs. 3, 0 vs. 1%; p = .22). Conclusions UGAVA is a safe approach for CIED implantation and helps prevent an extra incision if a barrier is identified changing laterality preincision.

Cardiogenic shock (CS) portends an extremely high mortality of nearly 50% during index hospitalization. Prompt diagnoses of CS, its underlying etiology, and efficient implementation of treatment modalities, including mechanical circulatory support (MCS), are critical especially in light of such high predicted mortality. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) provides the most comprehensive cardiopulmonary support in critically ill patients and hence has seen a steady increase in its utilization over the past decade. Hence, a good understanding of VA-ECMO, its role in treatment of CS, especially when compared with other temporary MCS devices, and its complications are vital for any critical care cardiologist. Our review of VA-ECMO aims to provide the same.

Introduction: Tricuspid valve (TV) regurgitation is the most common valvular pathology after orthotopic heart transplant (OHT). The number of transplants being performed is increasing with patients living longer after heart transplant. Data on TV surgery in OHT recipients is limited. Methods: We sought to analyze the outcomes of patients undergoing TV surgery from a large diverse, multicentric, nationwide cohort using the Nationwide Inpatient Sample (NIS) database. Results: A total of 42,766 TV repair or replacement (bioprosthetic and mechanical) involving adult patients (age ≥18 years) between 2007 and September 2015 were identified. Of these, 366 were performed in patients with OHT. TV repair was the most common surgery performed in both groups (OHT group and native heart group). Compared to the native group, patients with OHT had a significantly higher incidence of cardiogenic shock (20 vs. 11%, p = 0.024), acute kidney injury (AKI) (59 vs. 30%, p < 0.001), and AKI requiring hemodialysis (13 vs. 4%, p < 0.001). Also, the mean length of stay for the index admission was significantly longer in the OHT group (27 vs. 17 days, p = 0.008). The mortality rate was similar between the two groups (7 vs. 8%, p = 0.753). The number of TV surgeries performed in OHT patients from 2007 to 2014 have remained stable (p = 0.803) compared to those in native heart patients which showed a significantly increasing trend (p = 0.019) during the same time period. Conclusions: TV surgery remains an important treatment modality among the OHT population and carries a similar mortality during index hospitalization as that in native heart patients undergoing TV surgery.

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