Emergency Surgical Treatment and Triage: Targeting Optimal Outcomes for Emergency Surgical Patients From Index Encounter Through Definitive Care.

BACKGROUND: Patients with emergency surgical conditions (ESCs) experience higher complication rates than those without emergency conditions. Our purpose was to improve time-based key performance indicators (KPIs) of care for ESC patients, including diagnostic workup, empiric stabilization, and referral to definitive care. METHODS: A rapid response program (ESTAT) was developed to screen for and coordinate optimal, timely care for a spectrum of high-risk ESCs, from the patient's index clinical encounter up to definitive care. The Mann-Whitney test assessed whether any differences in KPIs were statistically significant (P < .05) before compared to after the implementation of ESTAT. RESULTS: 98 patients were identified: 44 in ESTAT group (70% age ≥55, 57% male); 54 in control group (57% age ≥55, 44% male). There were significant decreases from time of index clinical encounter to resuscitation (5 min. vs 34 min., P < .001), to diagnostic imaging (52 min. vs 1 hr. 19 min., P = .004), and to definitive care (2 hr. 17 min. vs 3 hr. 51 min., P = .007) in the ESTAT group compared to the control group, respectively. DISCUSSION: Improving time-based KPIs for delivery of clinical services is a common goal of medical emergency response systems (MERS) in numerous specialties. Implementation of an ESTAT program provides a screening tool for at-risk patients and reduces time to stabilize, diagnose and triage to definitive surgical intervention. These time benefits may ultimately translate to reduced complication rates for ESC patients. ESTAT may also represent a patient onboarding mechanism for surgical specialty verification programs promoted by quality improvement committees of various professional societies.

Tissue Doppler derived biphasic velocities during the pre and post-ejection phases: patterns, concordance and hemodynamic significance in health and disease.

BACKGROUND: Pre-(PRE) and post-ejection (POE) velocities by mitral annular tissue Doppler (TD) are biphasic and may be related to myocardial deformations. We investigated the predominance and concordance of TD-PRE and POE velocities and their effect on myocardial functions in controls and in heart failure (HF) patients. METHODS: Retrospectively, 84 HF patients [57.6 years, 28(33%) females, NYHA: 2.3 ± 0.6, EF: 55 ± 15%, 52(62%) preserved EF, and 32(38%) reduced EF], 42 normal young controls, and 26 asymptomatic age matched controls were included. Echocardiography was done and from mitral annular tissue Doppler recordings, the biphasic PRE and POE velocity signals were identified and compared between groups. RESULTS: While controls had almost always predominantly positive PRE and negative POE, HF had more negative PRE and positive POE. Moreover, almost all controls exhibited normal concordance (positive PRE and negative POE). HF exhibited more abnormal concordance which was significantly associated with worse NYHA, and parameters of diastolic and systolic functions. Opposite PRE and POE velocities correlated significantly in all groups (PREp vs POEn: young:r = 0.52, p < 0.001, age controls:r = 0.79, p < 0.001, HFpEF: r = 0.56, p < 0.001, HFrEF: r = 0.42, p = 0.018; PREn vs POEp: young: r = 0.25,p = 0.1, age controls: r = 0.42, p = 0.04, HFpEF: r = 0.43, p = 0.004, HFrEF: r = 0.61, p < 0.001) and the ratios PRE-P/N and POE-N/P correlated significantly with E/e' in HF only. CONCLUSIONS: In physiological state, TD signals are predominantly positive during PRE and negative during POE. Opposite PRE and POE velocities corelate, representing the PRE-generation and POE-reversal of shortening-stretch relationships, the attenuation of which in HF may be related to elevated LV filling pressures. In HF, partially or completely reversed concordance of PRE and POE is associated with progressive worsening of clinical and hemodynamic profiles.

Comprehensive Structural and Biochemical Analysis of the Terminal Myxalamid Reductase Domain for the Engineered Production of Primary Alcohols.

The terminal reductase (R) domain from the non-ribosomal peptide synthetase (NRPS) module MxaA in Stigmatella aurantiaca Sga15 catalyzes a non-processive four-electron reduction to produce the myxalamide family of secondary metabolites. Despite widespread use in nature, a lack of structural and mechanistic information concerning reductive release from polyketide synthase (PKS) and NRPS assembly lines principally limits our ability to redesign R domains with altered or improved activity. Here we report crystal structures for MxaA R, both in the absence and, for the first time, in the presence of the NADPH cofactor. Molecular dynamics simulations were employed to provide a deeper understanding of this domain and further identify residues critical for structural integrity, substrate binding, and catalysis. Aggregate computational and structural findings provided a basis for mechanistic investigations and, in the process, delivered a rationally altered variant with improved activity toward highly reduced substrates.