The Effect of Modified Ultrafiltration on Serum Vancomycin Levels During Cardiopulmonary Bypass in Cardiac Surgery.

OBJECTIVE: The aim of this study was to investigate whether the use of modified ultrafiltration at the end of cardiopulmonary bypass for cardiac surgical procedures significantly changes vancomycin serum concentrations. DESIGN: Prospective study. SETTING: Single tertiary cardiac center. PARTICIPANTS: Twenty-six elective adult patients undergoing cardiac surgery with cardiopulmonary bypass from April 2014 to April 2015. INTERVENTIONS: Serum vancomycin concentrations were measured just before cardiopulmonary bypass; during cardiopulmonary bypass at 5, 30, 60 minutes and then every 60 minutes; after completion of cardiopulmonary bypass before initiation of modified ultrafiltration; and at the end of modified ultrafiltration. MEASUREMENTS AND MAIN RESULTS: Seventeen patients received modified ultrafiltration at the end of cardiopulmonary bypass. Serum vancomycin concentrations prior to cardiopulmonary bypass (45.9 ± 17.3 µg/mL) were significantly higher (P < 0.0001) than each time point following cardiopulmonary bypass (5 min 20.4 ± 6.4 µg/mL, 30 min 18.8 ± 5.4 µg/mL, 60 min 16.6 ± 4.9 µg/mL, and 120 min 14.3 ± 4.7 µg/mL). In the modified ultrafiltration group, serum vancomycin concentrations were 14.7 ± 4.6 µg/mL prior to modified ultrafiltration and 13.9 ± 4.3 µg/mL after ultrafiltration; this difference was statistically significant (P  =  0.0288). The mean modified ultrafiltration volume was 465 ± 158 mL. CONCLUSIONS: Using modified ultrafiltration at the end of cardiopulmonary bypass significantly decreases serum vancomycin levels, but not by a clinically relevant amount. The decrease is to a concentration that is still significantly higher than the minimum inhibitory concentration for Staphylococcus epidermidis and Staphylococcus aureus; thus additional vancomycin administration is not recommended.

Evaluation of epiduroscopy for detection of vertebral canal and spinal cord lesions in dogs.

OBJECTIVE To evaluate the potential usefulness of epiduroscopy for clinical diagnosis and treatment of vertebral canal and spinal cord lesions in dogs. SAMPLE Cadavers of 6 mixed-breed dogs. PROCEDURES Dogs were positioned in sternal recumbency, and an endoscope was introduced into the lumbosacral epidural space. A fiberscope (diameter, 0.9 mm; length, 30 cm) was used for 3 dogs, and a videoscope (diameter, 2.8 mm; length, 70 cm) was used for the other 3 dogs. Visibility and identities of anatomic structures were recorded, and maneuverability of the endoscopes was assessed. Extent of macroscopic tissue damage was evaluated by manual dissection of the vertebral canal at the end of the procedure. RESULTS Intermittent saline (0.9% NaCl) solution infusion, CO2 insufflation, and endoscope navigation improved visualization by separating the epidural fat from the anatomic structures of interest. Images obtained with the fiberscope were small and of poor quality, making identification of specific structures difficult. Maneuverability of the fiberscope was difficult, and target structures could not be reliably reached or identified. Maneuverability and image quality of the videoscope were superior, and spinal nerve roots, spinal dura mater, epidural fat, and blood vessels could be identified. Subsequent manual dissection of the vertebral canal revealed no gross damage in the spinal cord, nerve roots, or blood vessels. CONCLUSIONS AND CLINICAL RELEVANCE A 2.8-mm videoscope was successfully used to perform epiduroscopy through the lumbosacral space in canine cadavers. Additional refinement and evaluation of the technique in live dogs is necessary before its use can be recommended for clinical situations.

Case report of a parturient with cyanotic congenital heart disease palliated with a Glenn procedure.

As the prevalence of adults with palliated congenital heart disease continues to increase, so, too, does the number of these patients who will become pregnant. Practicing physicians need to be familiar with the impact that normal physiologic changes associated with pregnancy and delivery has on patients with palliated congenital heart disease. The physiologic impact of pregnancy on a patient with palliated cyanotic congenital heart disease and the management of her delivery are presented.

Synthesis of site-specific antibody-drug conjugates using unnatural amino acids.

Antibody-drug conjugates (ADCs) allow selective targeting of cytotoxic drugs to cancer cells presenting tumor-associated surface markers, thereby minimizing systemic toxicity. Traditionally, the drug is conjugated nonselectively to cysteine or lysine residues in the antibody. However, these strategies often lead to heterogeneous products, which make optimization of the biological, physical, and pharmacological properties of an ADC challenging. Here we demonstrate the use of genetically encoded unnatural amino acids with orthogonal chemical reactivity to synthesize homogeneous ADCs with precise control of conjugation site and stoichiometry. p-Acetylphenylalanine was site-specifically incorporated into an anti-Her2 antibody Fab fragment and full-length IgG in Escherichia coli and mammalian cells, respectively. The mutant protein was selectively and efficiently conjugated to an auristatin derivative through a stable oxime linkage. The resulting conjugates demonstrated excellent pharmacokinetics, potent in vitro cytotoxic activity against Her2(+) cancer cells, and complete tumor regression in rodent xenograft treatment models. The synthesis and characterization of homogeneous ADCs with medicinal chemistry-like control over macromolecular structure should facilitate the optimization of ADCs for a host of therapeutic uses.