Effects of a single bolus of hydroxocobalamin on hemodynamics in vasodilatory shock.

PURPOSE: Hydroxocobalamin has been observed to cause transient hypertension in healthy subjects, but rigorous studies examining its efficacy are lacking. MATERIALS AND METHODS: Adults in shock who received hydroxocobalamin from 2017 to 2021 were analyzed retrospectively. Hourly hemodynamics from 24 h before and after treatment were collected, and the difference and hourly change of mean arterial pressure (MAP), systolic blood pressure (SBP), diastolic blood pressure (DBP), and norepinephrine-equivalent dose (NED) were examined in mixed-effects models. RESULTS: This study included 3992 hemodynamic data points from 35 patients and is the largest case series to date. In the mixed effects model, there was no difference in MAP 24-h after hydroxocobalamin administration (estimated fixed effect [EFE] -0.2 mmHg, p = 0.89). A two-piecewise mixed model found that the hourly change in MAP was not different from zero in either the pre-administration (EFE 0.0 mmHg/h, p = 0.80) or post-administration segments (EFE 0.0 mmHg/h, p = 0.55). Analysis of the SBP, DBP, and NED also found similar insignificant results. CONCLUSIONS: Although hydroxocobalamin has been observed to cause hypertension in healthy subjects, our results suggest that in patients with shock, hydroxocobalamin may not be effective in improving hemodynamics at 24 h after administration.

Renin Kinetics Are Superior to Lactate Kinetics for Predicting In-Hospital Mortality in Hypotensive Critically Ill Patients.

OBJECTIVES: Whole blood lactate concentration is widely used in shock states to assess perfusion. We aimed to determine if the change in plasma renin concentration over time would be superior to the change in lactate concentration for predicting in-hospital mortality in hypotensive patients on vasopressors. DESIGN: Prospective, observational cohort study. SETTING: Tertiary academic ICU. PATIENTS: Adult patients on vasopressors for greater than 6 hours to maintain a mean arterial pressure greater than or equal to 65 mm Hg during January 2020. INTERVENTIONS: Plasma renin concentrations were measured at enrollment and at 24, 48, and 72 hours. Whole blood lactate measurements were performed according to normal standard of care. Logistic regression was performed to evaluate whether the change in renin or lactate concentration could predict in-hospital mortality. Generalized estimating equations were used to analyze the association between renin and lactate concentration and in-hospital mortality. The area under the receiver operating characteristics curve was performed to measure the discriminative ability of initial and peak renin and lactate concentration to predict mortality. The association between renin and lactate concentration above the upper limit of normal at each timepoint with in-hospital mortality was also examined. MEASUREMENTS AND MAIN RESULTS: The study included 197 renin and 148 lactate samples obtained from 53 patients. The slope of the natural log (ln) of renin concentration was independently associated with mortality (adjusted odds ratio, 10.35; 95% CI, 1.40-76.34; p = 0.022), but the slope of ln-lactate concentration was not (adjusted odds ratio, 4.78; 95% CI, 0.03-772.64; p = 0.55). The generalized estimating equation models found that both ln-renin (adjusted odds ratio, 1.18; 95% CI, 1.02-1.37; p = 0.025) and ln-lactate (adjusted odds ratio, 2.38; 95% CI, 1.05-5.37; p = 0.037) were associated with mortality. Area under the receiver operating characteristics curve analysis demonstrated that initial renin could predict in-hospital mortality with fair discrimination (area under the receiver operating characteristics curve, 0.682; 95% CI, 0.503-0.836; p = 0.05), but initial lactate could not (area under the receiver operating characteristics curve, 0.615; 95% CI, 0.413-0.803; p = 0.27). Peak renin (area under the receiver operating characteristics curve, 0.728; 95% CI, 0.547-0.888; p = 0.01) and peak lactate (area under the receiver operating characteristics curve, 0.746; 95% CI, 0.584-0.876; p = 0.01) demonstrated moderate discrimination. There was no significant difference in discriminative ability between initial or peak renin and lactate concentration. At each study time point, a higher proportion of renin values exceeded the threshold of normal (40 pg/mL) in nonsurvivors than in survivors, but this association was not significant for lactate. CONCLUSIONS: Although there was no significant difference in the performance of renin and lactate when examining the absolute values of each laboratory, a positive rate of change in renin concentration, but not lactate concentration, over 72 hours was associated with in-hospital mortality. For each one-unit increase in the slope of ln-renin, the odds of mortality increased 10-fold. Renin levels greater than 40 pg/mL, but not lactate levels greater than 2 mmol/L, were associated with in-hospital mortality. These findings suggest that plasma renin kinetics may be superior to lactate kinetics in predicting mortality of hypotensive, critically ill patients.

Degenerative Mitral Valve Repair Simplified: An Evolution to Universal Artificial Cordal Repair.

BACKGROUND: Resectional and artificial cordal repair techniques are effective strategies for degenerative mitral valve (MV) repair. However, resectional repair requires a tailored approach using various techniques, whereas cordal repair offers a simpler, easily reproducible repair. The approach described in this study approach has evolved from resectional to cordal over time, and outcomes are compared between the eras. METHODS: Clinical and echocardiographic outcomes of all patients undergoing MV repair for degenerative mitral regurgitation (MR) from January 2004 to September 2017 were reviewed. Patients were stratified by era: from January 2004 to June 2011 (era 1; n = 405), resectional techniques were used in 62% and artificial cordal techniques were used in 38%. From July 2011 to September 2017 (era 2; n = 438), artificial cordal repair was used in 98% of patients. The primary outcome was repair failure, defined as greater than moderate MR or MV reoperation. RESULTS: Of 847 patients with degenerative MR, successful repair was achieved in 843 patients (99.5% repair rate). Leaflet prolapse was posterior in 66%, anterior in 8%, and bileaflet in 26%. Cardiopulmonary bypass time and cross-clamp times were shorter in era 2 (CPB: 109 [IQR, 92-128] minutes vs 97 [IQR, 76-121] minutes; P < .001; cross-clamp: 88 [IQR, 73-106] minutes vs. 79 [IQR, 61-99] minutes; P < .001). Predismissal echocardiography demonstrated no MR or trace MR in 95%, mild MR in 4.7%, and moderate MR in 0.3% of patients. Operative mortality was similar in the eras (0.5% vs 0.5%; P > .999). The rates of 5-year freedom from repair failure (95.1% vs 95.5%; P = .707), stroke (96.8% vs 95.3%; P = .538), and endocarditis (99.3% vs 99.7%; P = .604) were similar between the eras. CONCLUSIONS: Artificial cordal repair for all patients with degenerative MR simplifies MV repair and yields equivalent, excellent outcomes compared with a tailored resectional approach.

Enantioselective cis-ß-lactam synthesis by intramolecular C-H functionalization from enoldiazoacetamides and derivative donor-acceptor cyclopropenes.

ß-Lactam derivatives are produced through intermediate donor-acceptor cyclopropene intermediates in high yield, exclusive cis-diastereoselectivity, and high enantiocontrol in a chiral dirhodium carboxylate catalyzed intramolecular C-H functionalization reaction of enoldiazoacetamides.

A decade of Web Server updates at the Bioinformatics Links Directory: 2003-2012.

The 2012 Bioinformatics Links Directory update marks the 10th special Web Server issue from Nucleic Acids Research. Beginning with content from their 2003 publication, the Bioinformatics Links Directory in collaboration with Nucleic Acids Research has compiled and published a comprehensive list of freely accessible, online tools, databases and resource materials for the bioinformatics and life science research communities. The past decade has exhibited significant growth and change in the types of tools, databases and resources being put forth, reflecting both technology changes and the nature of research over that time. With the addition of 90 web server tools and 12 updates from the July 2012 Web Server issue of Nucleic Acids Research, the Bioinformatics Links Directory at http://bioinformatics.ca/links_directory/ now contains an impressive 134 resources, 455 databases and 1205 web server tools, mirroring the continued activity and efforts of our field.

The 2011 Bioinformatics Links Directory update: more resources, tools and databases and features to empower the bioinformatics community.

The Bioinformatics Links Directory continues its collaboration with Nucleic Acids Research to collaboratively publish and compile a freely accessible, online collection of tools, databases and resource materials for bioinformatics and molecular biology research. The July 2011 Web Server issue of Nucleic Acids Research adds an additional 78 web server tools and 14 updates to the directory at http://bioinformatics.ca/links_directory/.